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[(The)-270.6(initial)-268.7(priority)-268.3(of)-272.9(neonatal)-271.8(screening)-272.5(for)-268.2(CH)-269(should)]TJ
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[(be)-481.4(the)-482.6(detection)-486.1(of)-480.2(all)-477(forms)-484.5(of)-480.2(primary)-482.5(CHmild,)]TJ
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[(moderate,)-449(and)-448(severe;)-448.8(the)-448.1(most)-443.3(sensitive)-450(test)-449.1(for)-441(de-)]TJ
0 -1.1116 TD
[(tecting)-621(primary)-620.7(CH)-620.4(is)-618.4(measurement)-623.9(of)-618.5(thyrotropin)]TJ
T*
[(\(TSH\))-335.7(\(1/)]TJ
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1.653 0 TD
(\).)Tj
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7.9702 0 0 7.9702 69.7323 473.2723 Tm
()Tj
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9.843 0 0 9.843 78.633 471.9684 Tm
[(When)-290.1(nancial)-288.9(resources)-289.4(are)-287.8(available,)-294.9(we)-286.5(recommend)]TJ
0 -1.1116 TD
[(adding)-318.9(measurement)-318.6(of)-319(total)-318.1(or)-318.9(free)-317.7(thyroxine)-316.6(\(fT4\))-317.6(to)]TJ
T*
[(TSH,)-337(to)-330.6(screen)-338.2(for)-337.3(central)-334(CH)-338.2(\(2/)]TJ
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13.8867 0 TD
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-15.8968 -2.3557 TD
[(1.3.)-498.6(Postscreening)-635(strategies)-623.7(in)-624.4(special)-632.2(categories)-624.9(of)]TJ
-1.0137 -1.1116 TD
[(neonates)-339.4(at)-330.6(risk)-339.4(of)-330.6(CH)]TJ
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7.9702 0 0 7.9702 69.7323 400.8188 Tm
()Tj
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T*
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T*
-.0215 Tc
[(de)-6.5(tec)-6.5(t).3(ed)-183.9(by)-183.9(neo)-5.3(n).4(at)-5.4(al)-184(scr)-5.3(een)-5.3(in)-5.3(g,)-180.4(fo)-5.3(r)-178.1(i)-5.4(nst)-5.4(a)-.7(nc)-6.5(e)-179.3(p)-5.3(rem)-6.5(a)-.7(tu)-5.3(re,)-180.4(l)-5.4(ow)]TJ
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T*
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(*)Tj
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[(10)-274.6(to)-268.9(14)-274.6(days)-268.7(of)-274.6(age)-275.8(m).6(ay)-268.9(be)-270(considered)-268.9(\(1/)]TJ
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()Tj
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()Tj
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[(Th)19.6(e)-319(n)0(o)20.8(n)0(a)19.7(f)0(f)20.9(e)0(c)12.8(t)0(e)19.5(d)-317.9(si)20.9(bl)20.7(in)20.7(g)-317.9(o)0(f)-307.4(t)0(w)19.8(i)0(n)20.7(s)-317.7(sh)15.3(ou)20.8(ld)-307.6(be)-308.6(fo)20.9(ll)20.6(ow)20(ed)-308.6(up)]TJ
T*
[(fo)20.9(r)-260.3(p)0(o)20.8(s)0(s)15.5(i)0(b)20.7(l)0(e)-251.2(T)0(S)19.8(H)-261.2(el)19.5(ev)19.7(at)13.8(io)20.7(n)-260.3(l)0(a)19.6(t)0(e)19.6(r)-260.2(in)-250(li)20.6(fe)-251(\(2)15.1(/)]TJ
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16.5764 0 TD
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7.9702 0 0 7.9702 69.7323 269.2913 Tm
()Tj
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0 -1.1116 TD
[(TSH)-298.9(in)-290.3(TSH-based)-301.9(screening)-301.3(programs,)-296.6(should)-294.5(prompt)]TJ
T*
[(further)-579.1(evaluation)-579.3(for)-579.2(primary)-580.4(\(rare)-583.7(cases)-578.8(of)-578.1(false-)]TJ
T*
[(negative)-496.4(neonatal)-490.6(screening)-497.1(results\))-493.6(and)-494(central)-495.2(CH,)]TJ
0 -1.1174 TD
[(particularly)-310.9(in)-307.6(children)-310.9(with)-310.8(a)-307.5(family)-308.7(history)-307.2(of)-307.4(central)]TJ
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[(CH)-332.4(\(2/)]TJ
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2.8338 0 TD
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(00\).)Tj
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8.9663 0 0 8.9663 69.7323 188.5605 Tm
[(2.)-501.1(Diagnostics)-332.7(and)-335.7(criteria)-332.5(for)-338.9(treatment)]TJ
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[(2.1.)-498.6(Biochemical)-501.9(criteria)-494.9(used)-494.9(in)-491.9(the)-488.4(decision)-495(to)-497.7(start)]TJ
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()Tj
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9.843 0 0 9.843 78.633 144.2267 Tm
[(A)-307.2(newborn)-309.2(with)-310.8(an)-308.6(abnormal)-312(neonatal)-312.1(screening)-312.8(result)]TJ
T*
[(should)-334.8(be)-331.7(referred)-340.5(to)-336.4(an)-331.7(expert)-337.3(center)-338.5(\(1/)]TJ
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16.9393 0 TD
(++)Tj
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7.9702 0 0 7.9702 69.7323 123.5905 Tm
()Tj
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[(An)-446.6(abnormal)-444.4(screening)-451(result)-445.5(should)-450(be)-441.1(followed)-448.8(by)]TJ
0 -1.1174 TD
[(conrmatory)-384.2(testing)-377.7(consisting)-380.8(of)-382.3(measurement)-382(of)-376.5(se-)]TJ
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[(rum)-332.8(fT4)-338.5(and)-332.8(TSH)-333.5(\(1/)]TJ
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8.8469 0 TD
(++)Tj
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7.9702 0 0 7.9702 69.7323 90.7653 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 78.633 89.4614 Tm
[(If)-583.9(the)-586.3(serum)-583.6(fT4)-586.2(concentration)-589.5(is)-583.9(below)-583.6(and)-580.4(TSH)]TJ
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[(clearly)-408.8(above)-405.3(the)-407.8(age-specic)-409.3(reference)-407.3(interval,)-412.3(then)]TJ
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[(levothyroxine)-489.3(\(LT4\))-485.9(treatment)-493(should)-484.6(be)-487.2(started)-493.9(im-)]TJ
T*
[(mediately)-337.6(\(1/)]TJ
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5.4199 0 TD
(+++)Tj
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()Tj
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9.843 0 0 9.843 329.6692 726.5195 Tm
[(If)-428.3(the)-419.3(serum)-428.1(TSH)-425.7(concentration)-428.3(is)]TJ
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14.9061 0 TD
(>)Tj
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[(20)-163.5(mU/L)-428.3(at)-423.9(con-)]TJ
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[(rmatory)-304.9(testing)-302.8(\(approximately)-302.7(in)-296.1(the)-304.1(second)-302.5(week)-301.3(of)]TJ
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[(life\),)-298.3(treatment)-297.2(should)-294.5(be)-291.3(started,)-295.7(even)-294.7(if)-296(fT4)-292.4(is)-290.1(normal)]TJ
T*
[(\(arbitrary)-341.8(threshold,)-337.1(expert)-331.6(opinion\))-337.3(\(2/)]TJ
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16.1272 0 TD
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7.9702 0 0 7.9702 320.8251 683.9431 Tm
()Tj
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[(If)-359.2(the)-361.7(serum)-359(TSH)-356.5(concentration)-359.2(is)-359.2(620)-165.7(mU/L)-359.2(beyond)]TJ
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[(the)-419.3(age)-420.3(of)-416.9(21)-416.9(days)-420.1(in)-417(a)-422.7(healthy)-419.2(neonate)-420.3(with)-420.2(an)-418.1(fT4)]TJ
T*
[(concentration)-261.2(within)-249.8(the)-258(age-specic)-253.8(reference)-257.5(interval,)]TJ
0 -1.1174 TD
[(we)-407.4(suggest)-411.8(to)-405.5(either)-406.6(start)-409.9(LT4)-408.9(treatment)-412.4(immediately)]TJ
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[(and)-280.9(retest,)-277.3(off-treatment,)-281.9(at)-280(a)-278.7(later)-278.8(stage,)-276.1(or)-278.6(to)-278.8(withhold)]TJ
T*
[(treatment)-239.6(but)-233.8(retest)-239.4(1)-237.2(t)0(o)-232.7(2)-231.5(weeks)-238.9(later)-238.4(and)-234.8(to)-232.7(re-evaluate)]TJ
T*
[(the)-465.4(need)-461.7(for)-458.3(treatment)-464.3(\(lack)-462.9(of)-457.2(evidence)-462.9(in)-463.1(favor)-461.6(or)]TJ
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[(tion\))-334(\(2/)]TJ
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3.3464 0 TD
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1.1059 0 TD
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7.9702 0 0 7.9702 320.8251 585.2975 Tm
()Tj
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[(In)-301.7(countries)-300.3(or)-295.9(regions)-302.5(where)-302.4(thyroid)-295.9(function)-304(tests)-300.3(are)]TJ
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[(not)-251.1(readily)-246.4(available,)-254.5(LT4)-247.6(treatment)-251.1(should)-248.5(be)-251(started)-252(if)]TJ
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[(lter)-548.1(paper)-549.2(TSH)-546.6(concentration)-555(is)]TJ
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[(40)-169.2(mU/L)-549.2(\(at)-546(the)]TJ
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[(moment)-661.2(of)-653(neonatal)-663.4(screening;)-659.6(arbitrary)-657.5(threshold,)]TJ
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[(If)-434.1(the)-430.8(serum)-433.9(fT4)-430.7(is)-434.1(low,)-428.2(and)-436.4(TSH)-431.4(is)-428.3(low,)-434(normal)-435.3(or)]TJ
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5.7943 0 TD
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(0\).)Tj
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7.9702 0 0 7.9702 320.8251 497.6503 Tm
()Tj
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9.843 0 0 9.843 329.6692 496.3463 Tm
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T*
[(function;)-639.2(if)-641.6(coexistent)-642.5(central)-639.2(adrenal)-639.1(insufciency)]TJ
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[(cannot)-239.5(be)-233.7(ruled)-237.2(out,)-231.5(LT4)-236.1(treatment)-239.6(must)-236(be)-233.7(preceded)-238.1(by)]TJ
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T*
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(+)Tj
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[(2.2.)-498.6(Communication)-433.4(of)-428.6(abnormal)-435.9(screening)-433.6(and)-429.5(conr-)]TJ
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[(matory)-336.9(results)]TJ
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7.9702 0 0 7.9702 320.8251 392.3148 Tm
()Tj
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9.843 0 0 9.843 329.6692 391.0109 Tm
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[(A)-15.7(n)-398.9(abn)-15.7(o)10.9(rmal)-414.3(neona)-15.7(t)9.6(a)-.7(l)-408.6(s)-15.7(c)9.9(r).5(een)-15.7(i)10.8(n).5(g)-408.5(r)-15.7(e)9.8(s).7(ul)-15.7(t)-398.3(s).7(h)-15.7(o)10.9(uld)-408.5(b)-15.7(e)-399.2(c)-.7(om-)]TJ
T*
-.0154 Tc
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T*
[(me)-15.8(n)9.6(t).3(ed)-264.6(with)-264.6(writ)-15.8(t)10.5(e)-.8(n)-258.8(i)-15.8(n)10.7(for)-15.8(m)9.6(a)-.8(tio)-15.8(n)-248.4(fo)-15.8(r)-248.4(t).3(he)-265.7(famil)-15.8(y)-248.5(\(2)-15.8(/)]TJ
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[(2.3.)-498.6(Imaging)-331.2(techn)-8(iques)-334.9(in)-330.6(CH)]TJ
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()Tj
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T*
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T*
[(as)-337.2(possible)-332.4(LT4)-334(dose)-339.4(titration)-334.2(\(2/)]TJ
/F4 1 Tf
13.6505 0 TD
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(00\).)Tj
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7.9702 0 0 7.9702 323.0361 617.3857 Tm
()Tj
/F3 1 Tf
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0 -1.1116 TD
[(reduced)-662(absorption,)-655(or)-658.8(increased)-659.6(metabolization)-661.3(of)]TJ
T*
[(thyroxine)-345.4(\(T4\))-339.6(by)-342(other)-340.8(disease)-345(\(e.g.,)-337.3(gastrointestinal\),)]TJ
0 -1.1174 TD
[(food)-413.3(or)-411.1(medication)-419.3(should)-409.7(be)-412.3(considered)-417.6(\(2/)]TJ
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18.6845 0 TD
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[(00\);)-407.7(in-)]TJ
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T*
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-.9043 -2.8165 TD
[(3.3.)-504.4(Treatment)-335.6(and)-331.6(monitoring)-334.6(of)-336.4(central)-338.4(CH)]TJ
/F13 1 Tf
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()Tj
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[(In)-255.6(severe)-257.5(forms)-254.2(of)-255.6(central)-259.1(CH)-251.8(\(fT4)]TJ
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14.1574 0 TD
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[(recommend)-349.9(to)-347.9(start)-346.5(LT4)-345.5(treatment)-349.1(as)-343(soon)-349.8(as)-343(possible)]TJ
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T*
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()Tj
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[(In)-526.3(milder)-527.6(forms)-524.9(of)-526.3(central)-529.8(CH,)-525.9(we)-522.6(suggest)-527(starting)]TJ
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[(g/kg)-292.5(per)-292.4(day\),)-291.2(to)]TJ
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[(avoid)-335.1(the)-332.9(risk)-338.4(of)-330.5(overtreatment)-343.1(\(1/)]TJ
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(++)Tj
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()Tj
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[(In)-457.2(newborns)-459.9(with)-460.5(central)-460.7(CH,)-456.8(we)-459.2(recommend)-459.3(moni-)]TJ
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[(toring)-323.6(treatment)-326(by)-324.7(measuring)-324.4(fT4)-327(and)-321.2(TSH)-327.8(according)]TJ
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T*
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[(age-specic)-472.7(reference)-470.6(interval;)-467.7(if)-468.8(TSH)-466(is)-468.7(low)-465.1(before)]TJ
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[(treatment,)-738.4(subsequent)-738.8(TSH)-736.7(determinations)-740.4(can)-737.1(be)]TJ
T*
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4.5214 0 TD
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(00\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 354.0471 Tm
()Tj
/F3 1 Tf
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0 -1.1116 TD
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T*
[(or)-333.4(t)-15.6(o)10.9(tal)-333.6(t)-15.6(r)10.9(i).4(io)-15.6(d)11(o).6(th)-15.6(y)11(ron)-15.6(i)10.9(n).6(e)-334.6(\().6(T3)-15.6(\))-323(can)-333.5(b)-15.6(e)-324.2(measu)-15.6(r)11(ed)-333.5(\(1)-15.6(/)]TJ
/F4 1 Tf
19.9228 0 TD
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(+)Tj
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[(00)-16.2(\))10.4(.)]TJ
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()Tj
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[(When)-434.1(fT4)-430.7(is)-428.4(around)-428.2(the)-430.8(lower)-433.9(limit)-427.7(of)-434.1(the)-430.8(reference)]TJ
0 -1.1174 TD
[(interval,)-608.2(then)-610.5(undertreatment)-609.1(should)-611.3(be)-602.4(considered,)]TJ
0 -1.1116 TD
[(particularly)-339.7(if)-336.4(TSH)]TJ
/F4 1 Tf
8.1385 0 TD
(>)Tj
/F3 1 Tf
.5529 0 TD
[(1.0)-166.9(mU/L)-336.1(\(1/)]TJ
/F4 1 Tf
5.2586 0 TD
(+)Tj
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(00\).)Tj
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7.9702 0 0 7.9702 323.0361 288.2834 Tm
()Tj
/F3 1 Tf
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[(the)-528.7(reference)-528.2(interval,)-533.3(then)-524.1(overtreatment)-533.1(should)-524.9(be)]TJ
0 -1.1116 TD
[(considered)-383(\(assuming)-386.4(that)-380.2(LT4)-380.1(has)-378.7(not)-377.8(been)-381.1(adminis-)]TJ
T*
[(tered)-370.8(just)-367.3(before)-366(blood)-368.5(withdrawal\),)-371.3(particularly)-368.5(if)-365.2(as-)]TJ
0 -1.1174 TD
[(sociated)-311.9(with)-310.8(clinical)-306.6(signs)-310.5(of)-307.4(thyrotoxicosis,)-313.9(or)-307.4(a)-307.5(high)]TJ
0 -1.1116 TD
[(fT3)-332.8(concentration)-341.9(\(1/)]TJ
/F4 1 Tf
8.6972 0 TD
(+)Tj
/F3 1 Tf
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(00\).)Tj
/F5 1 Tf
-10.1544 -2.8165 TD
[(3.4.)-504.4(Diagnostic)-324.3(re-evaluation)-323.2(of)-324.9(thyroid)-325.7(function)-321.4(beyond)]TJ
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[(the)-338.7(rst)-332.5(6)-335.2(months)-335.7(of)-330.6(life)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 178.4125 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 177.1086 Tm
[(When)-485.9(no)-486(denitive)-490.5(diagnosis)-483.2(of)-486(permanent)-492.8(CH)-482.2(was)]TJ
T*
[(made)-509.1(in)-509.2(the)-511.4(rst)-511(weeks)-509.6(or)-509(months)-508.9(of)-509(life,)-510.3(then)-506.8(re-)]TJ
T*
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0 -1.1174 TD
[(is)-267.1(indicated,)-264.9(particularly)-270.6(in)-261.5(children)-270.6(with)-264.7(a)-261.4(gland)]TJ
/F5 1 Tf
19.8825 0 TD
[(in)-267.3(situ)]TJ
/F3 1 Tf
-19.8825 -1.1116 TD
[(\(GIS\),)-326.3(and)-321.2(in)-324.9(those)-323.4(with)-328.1(presumed)-323.2(isolated)-328.1(central)-322.5(CH)]TJ
T*
(\(1/)Tj
/F4 1 Tf
1.1174 0 TD
(++)Tj
/F3 1 Tf
1.1001 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 112.6488 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 111.3448 Tm
[(Fo)21(r)-266(a)-267.2(pr)20.9(ec)18.5(is)15.1(e)-261.4(d)0(i)20.7(a)0(g)13.9(n)0(o)20.8(s)0(i)20.9(s)0(,)-257.8(L)0(T)18.5(4)-260.3(tr)15(ea)18.5(tm)19.5(en)19.7(t)-266.2(s)0(h)21(o)0(u)20.8(l)0(d)-255.8(b)0(e)-256.8(p)0(h)20.8(a)0(s)19.9(e)0(d)]TJ
0 -1.1116 TD
[(ou)20.8(t)-323.8(o)0(v)20.8(e)0(r)-308.6(a)-324.8(4)-317.9(t)0(o)-307.6(6)-323.6(we)18.8(ek)19.7(s)-323.4(p)0(e)19.7(r)0(i)20.7(o)0(d)-307.5(o)0(r)-313.2(j)0(u)20.7(s)0(t)-313.2(s)0(t)20.9(o)0(p)20.8(p)0(e)19.7(d)0(,)-309.8(a)0(n)19.7(d)-323.6(fu)20.9(ll)]TJ
T*
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0 -1.1174 TD
[(si)20.9(st)15.1(in)20.7(g)-323.6(o)0(f)-313.2(\()0(a)19.7(t)-323.8(le)19.6(as)14.1(t\))-313.3(fT)19.7(4)-323.6(a)0(n)19.7(d)-323.6(TS)19.8(H)-324.5(m)0(e)18.4(a)0(s)19.9(u)0(r)20.9(e)0(m)18.5(e)0(n)19.7(t)0(.)]TJ
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17.8378 0 TD
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()Tj
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[(10)-161.9(mU/)5(L)3.9(\),)]TJ
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(390)Tj
40.9535 0 TD
[(VAN)-332.3(TROTSENBURG)-337.1(ET)-338.7(AL.)]TJ
ET
endstream
endobj
132 0 obj
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T*
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[(10)-172.3(mU)-6.2(/L)-375.1(\(p)-5.3(ri)-5.4(ma)-6.5(ry)-373.9(CH)-6.2(\))-368.1(o).4(r)-373.9(f).5(T)-6.5(4)-368.2(ju)-5.3(s)-5.1(t)-368.3(ab)-5.3(o)-5.3(v).4(e)]TJ
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T*
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[(th)5.6(en)-334.2(co)5.6(nt)5.5(in)5.6(ue)-335.3(wi)5.5(th)5.6(drawal)-340.1(a)]TJ
11.3927 0 TD
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[(nd)-334.7(retest)-334.8(in)-334.7(an)5.1(ot)5(her)-340.4(3)-334.7(to)-334.7(4)]TJ
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[(0\))-5.7(.)]TJ
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[(If)-359.2(a)-353.6(child)-358.3(with)-356.9(no)-359.3(permanent)-360.3(CH)-355.4(diagnosis)-356.5(and)-361.6(a)-353.6(GIS)]TJ
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[(requires)-258.7(a)-261.4(LT4)-253.4(dose)-258.8(less)-258.7(than)-259.1(3)]TJ
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[(g/kg)-252.2(per)-257.9(day)-257.9(at)-262.7(the)-258(age)]TJ
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[(of)-313.2(6)-317.9(months,)-316.5(then)-316.7(re-evaluation)-318.8(can)-316.6(be)-314.4(done)-316.6(already)-316.6(at)]TJ
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[(that)-334.1(time)-335.4(\(1/)]TJ
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[(We)-282.1(recommend)-286.5(avoiding)-280.9(iodine)-284.5(as)-279.6(an)-285.6(antiseptic)-285.5(during)]TJ
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[(peri-)-329.3(and)-327(neonatal)-335.1(period,)-328.1(as)-325.7(it)-330.8(can)-328.2(cause)-331.3(transient)-329.2(CH)]TJ
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[(3.5.)-498.6(Treatment)-381.6(and)-377.7(monitoring)-380.7(of)-370.9(pregnant)-378.5(women)-383(with)]TJ
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[(In)-422.6(women)-423.5(with)-426(CH)-418.8(who)-424.6(are)-426.1(planning)-419.2(pregnancy,)-425.8(we)]TJ
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T*
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[(in)20.7(cl)19.5(ud)20.8(in)20.7(g)-323.6(m)0(o)19.6(r)0(p)15.1(h)0(o)20.8(l)0(o)20.7(g)0(y)-313.2(o)0(f)-313.2(t)0(h)20.7(e)-324.8(th)20.7(yr)15.1(oi)20.7(d)-323.6(g)0(l)20.7(a)0(n)19.7(d)-323.6(\(2)20.9(/)]TJ
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[(0\))20.9(.)]TJ
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()Tj
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[(Not)-326.8(only)-327.1(thyroid)-330.5(dyshormonogenesis,)-336.3(but)-326(also)-328(familial)]TJ
0 -1.1116 TD
[(occurrence)-460.3(of)-451.4(dysgenesis)-456.4(and)-459.5(central)-454.9(hypothyroidism)]TJ
T*
[(should)-334.8(lead)-335.2(to)-330.6(further)-337.2(genetic)-339.8(testing)-331.6(\(1/)]TJ
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16.5534 0 TD
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1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 607.2377 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 605.9337 Tm
[(Any)-441.9(syndromic)-450(association)-447.6(should)-444.3(be)-446.9(studied)-446.7(geneti-)]TJ
0 -1.1116 TD
[(cally,)-322.5(not)-326(only)-321.3(to)-324.9(improve)-321.2(genetic)-328.2(counseling,)-327.9(but)-320.2(also)]TJ
T*
[(to)-342.1(identify)-350.2(new)-345.2(candidate)-348.9(genes)-347.5(explaining)-347.8(the)-350.2(associ-)]TJ
0 -1.1174 TD
[(ation)-335.2(\(1/)]TJ
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1.1059 0 TD
(0\).)Tj
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7.9702 0 0 7.9702 72 563.4141 Tm
()Tj
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9.843 0 0 9.843 80.9008 562.1101 Tm
[(Further)-388.9(research)-387.6(is)-388(needed)-390.2(to)-388.2(better)-389.3(dene)-387.8(patients)-391.5(or)]TJ
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[(patient)-436.6(groups)-438.4(that)-437.8(will)-437.6(benet)-435.1(most)-437.5(from)-437.5(these)-439.7(new)]TJ
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[(diagnostic)-336.1(possibilities)-338.2(\(2/)]TJ
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[(5.3.)-498.6(Antenatal)-571.4(diagnostics,)-575.4(evaluation)-572.4(of)-572.5(fetal)-571.5(thyroid)]TJ
-1.0137 -1.1116 TD
[(function,)-336.3(and)-331.6(management)-337.8(of)-336.4(fetal)-335.4(hypothyroidism)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 72 485.2912 Tm
()Tj
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[(We)-431.8(re)14(co)19.7(mm)18.4(en)19.7(d)-444.6(a)0(n)19.7(t)0(e)19.6(n)0(a)19.7(t)0(a)19.6(l)-444.7(di)20.7(ag)19.7(no)15.1(si)20.9(s)-444.4(i)0(n)-434.3(c)0(a)18.5(s)0(e)19.9(s)-444.4(of)-434.1(go)20.8(it)14.8(er)]TJ
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[(ex)19.7(am)18.5(in)20.7(at)19.5(io)20.7(n)-369.7(o)0(f)-359.3(t)0(h)20.7(e)-370.9(fe)19.7(tu)15(s,)-355.7(in)-359.4(re)19.7(la)19.6(ti)14.8(on)-359.3(to)-359.4(th)20.7(yr)20.9(oi)20.7(d)-369.7(d)0(y)20.8(s)0(h)21(o)0(r)15.1(-)]TJ
T*
[(mo)19.6(no)20.8(ge)19.7(ne)19.7(si)20.9(s)-237(\()0(1)20.9(/)]TJ
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6.4451 0 TD
[(++)15.4(+)]TJ
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-.0202 Tc
[(\))-20.2(;)-241.4(a)-252.8(f)-20.2(a)-6.2(m)-20.2(il)-20.2(ia)-20.2(l)-242.6(r)-20.2(ec)-20.2(u)-6.3(r)-20.2(re)-20.2(nc)-20.2(e)-243.6(o)-20.2(f)-247(C)-20.2(H)-243.2(d)-20.2(ue)-258.6(t)-20.2(o)]TJ
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[(dy)20.8(sh)21(or)20.9(mo)19.6(no)15.1(ge)19.7(ne)19.7(si)20.9(s)-352.2(\()0(2)20.9(5)0(%)-343.1(r)0(e)19.7(c)0(u)19.7(r)0(r)20.9(e)0(n)19.7(c)0(e)-344.3(r)0(a)19.7(t)0(e)19.6(\))-352.4(\(1)20.9(/)]TJ
/F4 1 Tf
18.3619 0 TD
[(++)15.4(+)]TJ
/F3 1 Tf
1.63 0 TD
[(\);)-342.1(an)19.7(d)]TJ
-19.9919 -1.1116 TD
[(kn)20.8(ow)20(n)-502.2(d)0(e)19.7(f)0(e)14(c)0(t)19.5(s)-502(of)-491.7(ge)13.9(ne)19.7(s)-502(i)0(n)20.7(v)0(o)20.8(l)0(v)15(e)0(d)-492.9(i)0(n)-491.9(t)0(h)20.7(y)0(r)15.1(o)0(i)20.7(d)-502.2(fu)20.9(nc)19.7(ti)14.8(on)]TJ
T*
[(or)-549.3(de)13.9(ve)19.7(lo)20.7(pm)19.6(en)19.7(t)-565.7(w)0(i)19.8(t)0(h)-549.5(p)0(o)15.1(t)0(e)19.6(n)0(t)20.7(i)0(a)19.6(l)-565.7(ge)19.7(rm)19.7(li)20.6(ne)-556.3(tr)20.7(an)19.7(sm)19.8(is)20.9(si)15.1(on)]TJ
T*
[(\(1)20.9(/)]TJ
/F4 1 Tf
1.0828 0 TD
(++)Tj
/F3 1 Tf
1.0828 0 TD
[(0\))15.1(.)]TJ
-1.0483 -1.1174 TD
.0128 Tc
[(S)-5.4(p).2(e)-6.7(c)-1(ia)-6.7(l)-322.5(i).1(s)-5.4(s).4(u)-5.6(e)-1(s)-322.2(s)-5.4(ho)-5.6(ul)-5.7(d)-322.4(b).2(e)-323.5(c)-6.7(on)-5.6(si)-5.7(der)-5.5(e)-1(d)-322.4(f)-5.5(or)-322.3(s)-5.4(y).2(n)-5.6(d).2(r)-5.5(o).2(mi)-5.7(c)]TJ
-1.0079 -1.1116 TD
.013 Tc
[(cas)-5.2(es)-368(wi)-5.5(th)-368.2(po)-5.4(te)-6.5(nti)-5.5(a)-.8(l)-368.4(m)-.8(o)-5.4(r).4(ta)-6.5(li)-5.5(ty)-368.2(an)-5.4(d)-362.5(p)-5.4(os)-5.2(si)-5.5(ble)-369.4(g).4(e)-6.5(r).4(m)-6.6(lin)-5.4(e)]TJ
T*
0 Tc
[(m)15(o)16.2(s)16.4(a)15(ic)25.3(i)16.1(s)16.4(m)-417(\()16.2(a)15(s)-415.6(fo)26.6(r)]TJ
/F5 1 Tf
7.6892 0 TD
-.0151 Tc
[(NKX2)-15.1(-)11.5(1)]TJ
/F3 1 Tf
3.6229 0 TD
-.0159 Tc
[(gene)-432.9(mut)-15.9(a)9.4(tio)-15.9(n)10.7(/).2(del)-15.9(e)9.4(tio)-15.9(n)-415.5(a)-15.9(n)9.5(d)]TJ
-11.3121 -1.1174 TD
[(sever)-16(e)-238.2(pul)-16(m)9.2(onar)-16(y)-237(dys)-16(f)10.8(unct)-16(i)10.3(on)-247.5(w)-16(i)9.6(th)-247.5(po)-16(s)10.8(s).4(i)-16(b)10.5(le)-248.6(tr)-16(a)9.5(n).2(smi)-16(s)10.7(si)-16(o)10.5(n)]TJ
0 -1.1116 TD
[(thro)-15.9(u)10.7(g).3(h)-264.7(g).3(e)-15.9(r)9.6(mlin)-15.9(e)-255.4(m)-.9(osai)-15.9(c)9.4(i).2(sm)-15.9(\))9.5(.)-267(In)-264.7(suc)-15.9(h)-255.4(cir)-15.9(c)9.6(umst)-15.9(a)9.4(n).3(ces)-15.9(,)-250.6(t)-15.9(h)10.6(e)]TJ
T*
-.0161 Tc
[(disc)-16.1(u)9.3(ssi)-16.1(o)10.4(n)-293.7(of)-293.6(t)-16.1(h)10.4(e)-294.8(pren)-16.1(a)9.3(tal)-293.8(d)-16.1(i)10.4(a)-1.1(gno)-16.1(s)10.7(i)0(s)-293.5(s)-16.1(h)10.7(oul)-16.1(d)-283.4(b).1(e)-294.8(ope)-16.1(n)9.3(.)-290.2(T)-16.1(h)9.3(e)]TJ
0 -1.1174 TD
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[(thera)-15.6(p)9.8(eut)-15.6(i)10.7(c)-755.1(m)-.6(a)-15.6(n)9.8(ageme)-15.6(n)9.8(t)-754.1(o)-15.6(f)-743.5(af)-15.6(f)11.1(ect)-15.6(e)9.7(d)-753.9(f)-15.6(e)9.9(tus)-15.6(e)10(s)-759.5(s).8(hou)-15.6(l)10.9(d)]TJ
0 -1.1116 TD
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[(comply)-339.5(wi)-15.9(t)10.4(h)-333.8(t)-15.9(h)10.6(e)-334.9(l)-15.9(a)9.4(w)-.6(s)-339.3(i).2(n)-339.5(forc)-15.9(e)-325.7(i).2(n)-339.5(t).2(h)-15.9(e)-324.5(cou)-15.9(n)10.7(try)-339.5(c)-.9(on)-15.9(c)9.5(e)-.9(rn)-15.9(e)9.5(d)]TJ
T*
-.0162 Tc
(\(1/)Tj
/F4 1 Tf
1.0655 0 TD
0 Tc
(++)Tj
/F3 1 Tf
1.0771 0 TD
-.016 Tc
[(0\).)-244.1(T)-16(h)9.4(e)-242.9(f).2(a)-16(m)8.2(ilia)-16(l)-232.6(r).2(e)-16(c)8.3(urr)-16(e)9.5(n).2(ce)-248.6(of)-241.7(CH)-248.4(due)-248.6(to)-247.5(dysg)-16(e)9.4(nesi)-16(s)]TJ
-2.1426 -1.1116 TD
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[(\(2%)-473(of)-471.9(famil)-15.8(i)10.5(al)-472(occu)-15.8(r)10.8(r).4(en)-15.8(c)9.6(e)-.8(s\))-471.9(re)-15.8(q)9.6(u).4(ir)-15.8(e)9.7(s)-471.7(furt)-15.8(h)10.7(e)-.8(r)-471.9(s).6(tu)-15.8(d)10.8(y)-471.9(to)]TJ
0 -1.1174 TD
0 Tc
[(d)16.2(e)15(t)16.1(e)15(rm)25.4(i)16.1(n)16.2(e)-417(t)16.1(h)16.2(e)-411.2(fe)25.5(a)15(s)16.4(ib)26.5(i)16.1(l)16.1(i)0(t)26.3(y)-410(an)25.4(d)-410(c)15(li)26.3(n)16.2(i)16.1(ca)24.3(l)-410.2(r)16.2(el)25.3(e)15(v)16.2(a)15(n)0(c)25.4(e)-411.2(fo)26.6(r)-410(a)15(n-)]TJ
0 -1.1116 TD
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[(tenat)-15.6(a)9.7(l)-333.6(d).6(et)-15.6(e)9.7(c)-.6(tio)-15.6(n)11(.)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 72 266.0598 Tm
0 Tc
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 264.8125 Tm
[(For)-348.7(the)-344.4(evaluation)-354.7(of)-347.7(fetal)-347.9(thyroid)-347.8(volume,)-352.4(we)-349.8(recom-)]TJ
0 -1.1174 TD
[(mend)-289(ultrasound)-294.4(scans)-289.7(at)-291.5(20)-290.2(to)-290.3(22)-284.4(gestational)-298.2(weeks)-290.7(to)]TJ
0 -1.1116 TD
[(detect)-419.3(fetal)-422.8(thyroid)-422.6(hypertrophy)-422.3(and)-419.2(potential)-427.5(thyroid)]TJ
T*
[(dysfunction)-243.7(in)-244.2(the)-246.5(fetus.)-240.4(Goiter)-245(or)-244.1(an)-245.3(absence)-248.3(of)-244.1(thyroid)]TJ
0 -1.1174 TD
[(tissue)-664.2(can)-662.2(also)-662.1(be)-660(documented)-661(by)-664.6(this)-661.1(technique.)]TJ
0 -1.1116 TD
[(Measurements)-244.4(should)-236.9(be)-239.5(made)-244.1(as)-239.3(a)-238.4(function)-240.6(of)-238.3(GA,)-237.8(and)]TJ
T*
[(thyroid)-342(perimeter)-354.7(and)-344.3(diameter)-347.8(should)-346.4(be)-348.9(measured)-347.4(to)]TJ
0 -1.1174 TD
[(document)-335(goiter)-336.3(\(1/)]TJ
/F4 1 Tf
8.0809 0 TD
(+++)Tj
/F3 1 Tf
1.6588 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 178.4125 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 177.1086 Tm
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[(If)-201.4(a)-196.8(\()-5.6(la)-6.8(rge)-6.8(\))-195.7(f)-5.6(e)-1(ta)-6.8(l)-195.8(g)-5.6(oit)-5.7(e)-1(r)-201.4(i)0(s)-201.3(d).1(i)-5.7(a)-1(gn)-5.6(ose)-6.8(d).1(,)-198(p)-5.6(ren)-5.6(a)-1(ta)-6.8(l)-195.8(c)-6.8(are)-202.6(s).3(h)-5.6(oul)-5.7(d)-195.7(b)-5.6(e)]TJ
0 -1.1116 TD
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[(pr)-5.3(ovi)-5.4(ded)-270.3(i)-5.4(n)-270.3(a)-271.4(s)-5.1(p).4(ec)-6.5(ial)-5.4(i).3(ze)-6.5(d)-270.3(c)-.7(e)-6.5(n).4(te)-6.5(r)-270.2(o).4(f)-276(p).4(re)-6.5(nat)-5.4(a)-.7(l)-270.4(c)-6.5(are)-271.4(\()-5.3(1/)]TJ
/F4 1 Tf
19.8479 0 TD
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(+++)Tj
/F3 1 Tf
1.5954 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 156.4724 Tm
0 Tc
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 155.2252 Tm
[(We)-443.4(recommend)-447.8(cordocentesis,)-448.5(rather)-446.7(than)-443.4(amniocen-)]TJ
0 -1.1174 TD
[(tesis,)-246.1(as)-245.1(the)-246.5(reference)-251.8(method)-245.3(for)-245.1(assessing)-247.7(fetal)-250(thyroid)]TJ
0 -1.1116 TD
[(function.)-295.9(Norms)-295.4(have)-294.7(been)-294.7(established)-303.6(as)-291.2(a)-296(function)-298.2(of)]TJ
T*
[(GA.)-479.7(This)-483.6(examination)-489.5(should)-478.8(be)-487.2(carried)-483.6(out)-481.5(only)-482.6(if)]TJ
0 -1.1174 TD
[(prenatal)-335.1(intervention)-338.6(is)-336.2(considered)-337(\(1/)]TJ
/F4 1 Tf
15.5512 0 TD
(+++)Tj
/F3 1 Tf
1.6588 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 101.707 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 100.4031 Tm
[(In)-226.8(m)15(o)0(s)15.3(t)-231.6(ca)12.8(se)19.9(s,)-223.2(fe)19.7(ta)13.8(l)-231.6(t)0(h)20.7(y)0(r)15.1(o)0(i)20.7(d)-231.5(fu)15.1(nc)19.7(ti)20.6(on)-226.8(ca)18.5(n)-237.2(b)0(e)-222.2(i)0(n)20.7(f)0(e)14(r)0(r)20.9(e)0(d)-228(f)0(r)20.9(o)0(m)]TJ
0 -1.1116 TD
[(co)19.7(nt)20.7(ex)19.7(t)-266.2(a)0(n)19.7(d)-266(ul)20.7(tr)20.7(as)14.1(ou)20.8(nd)-255.6(cr)19.7(it)20.6(er)19.7(ia)13.8(,)-262.6(a)0(n)19.7(d)-266(fe)19.7(ta)19.6(l)-266.2(b)0(l)20.7(o)0(o)20.8(d)-266(sa)19.9(mp)19.6(li)14.8(ng)]TJ
0 -1.1174 TD
[(is)20.9(,)-326(t)0(h)20.7(e)0(r)19.7(e)0(f)19.7(o)0(r)20.9(e)0(,)-316.7(o)0(n)20.8(l)0(y)-313.3(e)0(x)19.7(c)0(e)18.5(p)0(t)14.9(i)0(o)20.7(n)0(a)19.7(l)0(l)20.6(y)-323.6(re)19.7(qu)20.8(ir)15(ed)-314.4(\(2)20.9(/)]TJ
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17.7053 0 TD
(++)Tj
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1.0828 0 TD
[(0\))15.1(.)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 72 68.8252 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 67.5212 Tm
[(We)-696.8(strongly)-700(recommend)-701.2(fetal)-699.2(treatment)-706.2(by)-699.1(intra-)]TJ
0 -1.1116 TD
[(amniotic)-329.5(T4)-331.7(injections)-330.4(in)-330.6(a)-330.6(euthyroid)-328.1(pregnant)-333.8(woman)]TJ
25.504 67.9242 TD
[(with)-483.6(a)-480.3(large)-480.2(fetal)-486.1(goiter)-480.3(associated)-487.8(with)-483.6(hydramnios)]TJ
0 -1.1174 TD
[(and/or)-480.2(tracheal)-480.2(occlusion;)-480.1(in)-480.4(a)-474.6(hypothyroid)-478.9(pregnant)]TJ
0 -1.1116 TD
[(woman,)-329(we)-326.8(recommend)-332.6(to)-324.9(treat)-330.6(the)-327.1(woman)-331.3(\(rather)-332.6(the)]TJ
T*
[(fetus\))-335.9(with)-333.8(T4)-337.5(\(1/)]TJ
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7.2918 0 TD
(++)Tj
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1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 682.5825 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 681.3352 Tm
[(For)-366(goitrous)-366(nonimmune)-365(fetal)-365.2(hypothyroidism)-368.2(leading)]TJ
0 -1.1174 TD
[(to)-543.7(hydramnios,)-546.6(we)-545.6(recommend)-545.7(intra-amniotic)-550.6(injec-)]TJ
0 -1.1116 TD
[(tions)-408.8(of)-411.1(LT4)-408.9(to)-405.5(decrease)-417.6(the)-407.8(size)-409.8(of)-411.1(the)-407.8(fetal)-411.2(thyroid)]TJ
T*
[(gland.)-453.7(The)-454.9(injections)-457.2(should)-455.8(be)-458.4(performed)-456.9(by)-451.5(multi-)]TJ
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[(disciplinary)-338.4(specialist)-337.2(teams)-337.3(\(1/)]TJ
/F4 1 Tf
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(+++)Tj
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()Tj
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(l)Tj
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[(amniotic)-583(injections.)-575.8(The)-581.6(risks)-575.4(to)-578.3(the)-580.6(fetus)-576.8(and)-580.4(the)]TJ
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T*
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(00\).)Tj
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[(1.2.)-498.6(Analytical)-586.1(methodology)-585(and)-580.4(effectiveness)-590.2(of)-578.1(CH)]TJ
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[(1.3.)-498.6(Postscreenin)-10.6(g)-358.2(strategies)-371.6(in)-359.4(special)-368.4(categories)-367(of)-359.3(ne-)]TJ
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[(screening)-370.4(prevent)-373(irreversible)-368.1(neurodevelopmental)-372.8(de-)]TJ
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[(where)-596.2(it)-584.2(has)-591.8(been)-588.5(established.)-595(Improved)-592.9(developmental)]TJ
T*
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T*
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T*
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T*
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[(increased)-290.9(risk)-280.8(of)-278.6(TH)-280.7(deciency.)]TJ
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[(strategy;)-484.7(based)-479.9(on)-474.5(data)-479.2(from)-477.9(a)-480.3(number)-481.3(of)-480.2(screening)]TJ
T*
[(programs,)-331.2(the)-327.1(incidence)-337.4(of)-324.7(primary)-332.7(CH)-326.6(lies)-333.9(between)-329(1)]TJ
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(*)Tj
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[(moderate,)-449(and)-448(severe;)-448.8(the)-448.1(most)-443.3(sensitive)-450(test)-449.1(for)-446.7(de-)]TJ
T*
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(+++)Tj
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(\).)Tj
/F6 1 Tf
8.9663 0 0 8.9663 62.022 749.6502 Tm
(392)Tj
40.9535 0 TD
[(VAN)-332.3(TROTSENBURG)-337.1(ET)-338.7(AL.)]TJ
ET
endstream
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BT
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[(When)-290.1(nancial)-288.9(resources)-289.4(are)-287.8(available,)-294.9(we)-286.5(recommend)]TJ
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[(adding)-347.7(measurement)-353.2(of)-347.7(total)-346.9(or)-347.7(fT4)-350(to)-347.9(TSH,)-348.5(to)-347.9(screen)]TJ
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(++)Tj
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(Evidence.)Tj
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[(Since)-364.9(the)-367.5(introduction)-372(of)-365(neonatal)-369.7(screening)]TJ
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[(TSH,)-394.5(gradually)-392.6(evolving)-390.4(into)-390.6(TSH)-396.9(only,)-388.1(its)-389.3(incidence)-395(and)]TJ
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T*
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(*)Tj
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T*
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[(scr)13(een)11.7(ing)-389.3(TSH)-391.1(cut)12.7(-of)14(f)-398.5(val)12.7(ue)13.9(s,)-396(res)13(ult)13.7(ing)-389.3(in)-394(the)-390.5(de)13.9(tec)11.5(tio)13.7(n)-398.5(o)0(f)]TJ
T*
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T*
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[(and)-234.9(thu)13.8(s)-242.8(env)12.8(iro)13.9(nm)13.9(ent)12.7(al,)-237.3(et)13.8(hni)13.8(c,)-241.8(an)13.9(d)-243(gen)12.8(eti)12.6(c)-244.2(fac)11.7(tor)13.9(s)-237.1(sho)14.2(uld)-233.8(be)]TJ
T*
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/F5 1 Tf
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[(DUO)11.4(X2/)12.7(DUO)11.4(XA2)]TJ
/F3 1 Tf
7.9196 0 TD
[(var)12.8(ies)-522.8(wid)13(ely)-528.7(bet)12.7(we)13(en)-533.3(ind)13.8(ivi)13.7(dua)12.8(ls)-526.3(and)]TJ
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[(DUO)11.4(X)]TJ
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T*
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T*
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T*
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T*
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/F4 1 Tf
10.091 0 TD
()Tj
/F3 1 Tf
.7142 0 TD
[(T4)19.6(-b)20.9(in)20.7(di)20.7(ng)-393.9(gl)20.7(ob)20.8(ul)15(in)-388.2(pr)15.1(ov)20.8(id)20.7(es)-394.8(th)20.7(e)]TJ
-10.8052 -1.1116 TD
[(po)15.1(te)19.5(nt)20.7(ia)19.6(l)-306.5(t)0(o)-296.1(d)0(i)15(a)0(g)19.7(n)0(o)20.8(s)0(e)-296.9(c)0(e)18.5(n)0(t)14.9(r)0(a)19.7(l)-306.5(CH)18.9(.)-308.7(A)0(l)19.8(t)0(h)20.7(o)0(u)20.8(g)0(h)-301.7(s)0(l)20.9(i)0(g)20.7(h)0(t)20.7(l)0(y)]TJ
/F4 1 Tf
20.8098 0 TD
(>)Tj
/F3 1 Tf
.5414 0 TD
[(50)20.8(%)-307.4(o)0(f)]TJ
-21.3512 -1.1174 TD
[(ne)13.9(on)20.8(at)19.5(es)-193.2(wi)19.8(th)-186.6(ce)12.8(nt)20.7(ra)19.7(l)-202.8(C)0(H)-188.4(h)0(a)19.7(v)0(e)-193.4(m)0(o)19.6(d)0(e)19.7(r)0(a)19.7(t)0(e)19.6(-)0(t)15(o)0(-)20.9(s)0(e)19.9(v)0(e)19.7(r)0(e)-193.4(C)0(H)18.9(,)-199.3(th)15(at)-187.8(is)15.1(,)]TJ
0 -1.1116 TD
[(a)-296()0(r)21(s)0(t)-284.4(d)0(i)20.7(a)0(g)19.7(n)0(o)15.1(s)0(t)20.9(i)0(c)-285.7(f)0(T)19.7(4)-294.8(co)19.7(nc)19.7(en)19.7(tr)20.7(at)19.5(io)15(n)-289.1(o)0(f)-284.4(5)0()20.8(1)0(0)-146.2(p)0(m)19.6(o)0(l)14.9(/)0(L)-280(o)0(r)-284.4(l)0(o)20.7(w)0(e)18.8(r)0(,)]TJ
T*
[(an)13.9(d)-306.4(c)0(e)18.5(n)0(t)20.7(r)0(a)19.7(l)-306.5(CH)-297.8(is)-295.9(li)20.6(ke)13.9(ly)-296.1(to)-296.1(be)-297.1(as)19.9(so)21(ci)19.5(at)13.8(ed)-297.1(wi)19.8(th)-296.1(ot)20.7(he)19.7(r)-306.3(p)0(i)20.7(t)0(u)15(i)0(t)20.6(a)0(r)19.7(y)]TJ
0 -1.1174 TD
[(ab)13.9(no)20.8(rm)19.6(al)19.5(it)20.6(ie)19.6(s,)-292.3(th)20.7(is)-295.9(di)20.7(ag)19.7(no)20.8(si)15.1(s)-300.4(i)0(s)-290.1(o)0(f)15.1(t)0(e)19.6(n)-300.6(de)19.7(la)19.6(ye)19.7(d)-306.4(\()0(2)20.9(0)0(,)18.5(2)0(1)20.8(\))0(.)-292.5(T)0(h)19.6(e)0(r)19.7(e)0(-)]TJ
0 -1.1116 TD
[(fo)15.1(re)19.7(,)-372(d)0(e)19.7(t)0(e)19.6(c)0(t)13.8(i)0(o)20.7(n)-369.7(of)-365(ce)18.5(nt)15(ra)19.7(l)-375.6(C)0(H)-361.2(b)0(y)-365.1(n)0(e)19.7(o)0(n)20.8(a)0(t)13.8(a)0(l)-360.6(s)0(c)14.1(r)0(e)19.7(e)0(n)19.7(i)0(n)20.7(g)-375.5(ha)19.7(s)-375.3(t)0(h)20.7(e)]TJ
T*
[(po)15.1(te)19.5(nt)20.7(ia)19.6(l)-335.3(t)0(o)-330.6(p)0(r)20.9(e)0(v)19.7(e)0(n)19.7(t)-335.3(th)20.7(e)-342.1(n)0(e)19.7(u)0(r)20.9(o)0(d)20.8(e)0(v)19.7(e)0(l)19.6(o)0(p)15.1(m)0(e)18.4(n)0(t)20.7(a)0(l)-326(s)0(e)19.9(q)0(u)20.8(e)0(l)13.8(a)0(e)-327.1(o)0(f)-324.7(T)0(H)]TJ
0 -1.1174 TD
[(de)13.9(c)19.8(ie)19.6(nc)19.7(y)-248.8(a)0(n)19.7(d)-243(as)19.9(so)15.3(ci)19.5(at)19.5(ed)-239.5(mo)19.6(rb)20.9(id)20.7(it)20.6(ie)19.6(s.)-240.5(Th)19.6(e)-244.2(r)0(e)19.7(p)0(o)15.1(r)0(t)20.7(e)0(d)-239.5(i)0(n)20.7(c)0(i)19.5(d)0(e)19.7(n)0(c)19.7(e)]TJ
0 -1.1116 TD
[(of)-411.1(ce)18.5(nt)20.7(ra)19.7(l)-421.7(C)0(H)-407.3(d)0(e)19.7(t)0(e)19.6(c)0(t)13.8(e)0(d)-406.5(t)0(h)20.7(r)0(o)20.9(u)0(g)15.1(h)-415.8(ne)19.7(on)20.8(at)13.8(al)-406.7(sc)19.9(re)19.7(en)13.9(in)20.7(g)-415.8(l)0(i)20.6(e)0(s)-412.1(b)0(e)19.7(-)]TJ
T*
[(tw)14.1(ee)18.5(n)-202.7(1)-208.4(in)-192.4(30)20.8(,0)18.5(00)-198(an)19.7(d)-208.4(1)-202.7(in)-198.2(16)20.8(,0)18.5(00)20.8(,)-205(d)0(e)19.7(p)0(e)19.7(n)0(d)20.8(i)0(n)15(g)-202.7(on)-198(th)20.7(e)-203.8(s)0(c)14.1(r)0(e)19.7(e)0(n)19.7(i)0(n)20.7(g)]TJ
0 -1.1174 TD
[(st)15.1(ra)19.7(te)19.6(gy)-226.8(\(2)15.1(2)20.8(26)20.8(\).)-229.1(Al)19.8(th)15(ou)20.8(gh)-226.8(ad)19.7(di)14.9(ti)20.6(on)20.8(al)-228.1(da)19.7(ta)-233.9(on)-226.8(th)15(e)-238.4(t)0(r)20.7(u)0(e)-233.7(c)0(l)19.6(i)0(n)20.7(i)0(c)19.6(a)0(l)]TJ
0 -1.1116 TD
[(be)13.9(ne)19.7(t)20.9(s)-311.9(a)0(n)19.7(d)-306.4(fa)14(ls)20.9(e-)19.7(po)20.8(si)15.1(ti)20.6(ve)-302.9(ra)19.7(te)19.6(s)-311.9(a)0(r)19.7(e)-307.5(re)14(qu)20.8(ir)20.7(ed)19.7(,)-308.7(c)0(e)12.8(n)0(t)20.7(r)0(a)19.7(l)-312.2(CH)-297.8(is)-301.6(a)]TJ
T*
[(po)15.1(te)19.5(nt)20.7(ia)19.6(l)-271.9(c)0(a)18.5(n)0(d)20.8(i)0(d)20.7(a)0(t)19.5(e)-273(fo)20.9(r)-271.8(n)0(e)19.7(o)0(n)20.8(a)0(t)19.5(a)0(l)-262.7(s)0(c)19.9(r)0(e)14(e)0(n)19.7(i)0(n)20.7(g)0(.)]TJ
1.0137 -1.1116 TD
[(Until)-289(2019,)-290.1(only)-286.8(supportive)-294.4(therapy)-292.4(was)-287.4(available)-297.2(for)-285.5(pa-)]TJ
-1.0137 -1.1174 TD
[(tients)-324.7(with)-328.1(MCT8)-324.3(deciency.)-323.2(This)-328.1(changed)-322.2(when)-329(a)-319(clinical)]TJ
0 -1.1116 TD
[(trial)-225.9(demonstrated)-231.1(that)-224.7(treatment)-228.1(with)-224.4(triiodothyroacetic)-232.6(acid)]TJ
T*
[(\(Triac\))-305(ameliorates)-306.1(key)-298.2(features)-305.9(of)-295.9(the)-298.3(peripheral)-302.7(thyrot)-6.8(oxi-)]TJ
0 -1.1174 TD
[(cosis)-271.4(and)-275.2(might)-266.2(benet)-273.9(brain)-271.7(development)-270.5(once)-271.7(treatment)-274.2(is)]TJ
0 -1.1116 TD
[(commenced)-224.4(early)-226.8(in)-215.4(life)-224.7(\(27\).)-220.9(Therefore,)-225.3(early)-221(recognition)-222.2(of)]TJ
T*
[(MCT8-affected)-644.2(children)-633.4(becomes)-640(of)-630(utmost)-635.7(importance)]TJ
0 -1.1174 TD
[(through)-255.5(T4)-251.1(and)-252.1(TSH)-252.9(neonatal)-254.5(screening)-255.2(eventhough)-255.4(the)-252.3(part)]TJ
0 -1.1116 TD
[(of)-209.5(the)-200.4(fetal)-209.6(component)-209.4(of)-203.8(the)-206.2(disease)-206.8(that)-207.4(can)-207.2(be)-204.9(alleviated)-206.3(by)]TJ
T*
[(Triac)-285.6(treatment)-285.7(remains)-281.9(to)-278.8(be)-285.6(determined.)]TJ
26.5234 67.9242 TD
.0121 Tc
[(P)5.4(i)-.6(t)5.1(f)-.5(alls)-242.2(in)-248.2(t)5.1(h)-.5(e)-243.6(n)-.5(ewb)5.2(orn)-242.4(scr)5.3(e)-1.7(eni)5.1(n)-.5(g)-248.2(d)5.2(o)-248.2(e)4.1(xi)5.1(st)-248.3(and)-248.2(c)4.1(an)-242.4(be)-243.6(due)]TJ
-1.0137 -1.1174 TD
.0071 Tc
[(to)-368.4(ab)-5.5(no)-5.5(r)-5.5(m)-1(a)-6.7(l)-362.8(T)-6.7(H)-363.5(b)-5.5(i).1(n)-5.5(d).2(i)-5.6(n).2(g)-368.4(g).2(l)-5.6(o)-5.5(bu)-5.5(li)-5.6(n,)-370.7(se)-6.7(ve)-6.7(re)-369.5(co)-5.5(nc)-6.7(o)-5.5(m)-1(i)-5.6(t).1(a)-6.7(n).2(t)-368.5(i).1(l)-5.6(l).1(-)]TJ
0 -1.1116 TD
.0117 Tc
[(n)4.8(e)-2.1(ss)5(es)5(,)-256.7(a)3.7(s)-259.9(w)4(el)4.7(l)-254.5(a)-2.1(s)-254.1(s)-.7(everal)-254.5(dru)4.8(gs)-254.1(and)-254.3(a)3.7(uto)4.8(a)-2.1(n)4.8(t)-1(i)4.7(bod)4.8(ies)-254.2(\()-.9(2)4.8(4)-.9(,28)4.8(\))-.9(.)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 310.8472 680.7683 Tm
0 Tc
[(1.3.)-496.4(Postscreening)-251.3(strategies)-244.9(in)-243.1(special)-245.4(categories)]TJ
0 -1.2203 TD
[(of)-330.2(neonates)-340.2(at)-329(risk)-335.5(of)-336.6(CH)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 320.8251 638.2487 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 329.6692 636.9447 Tm
[(Some)-611.4(groups)-611.2(of)-612.7(children,)-608.1(such)-610.1(as)-613.7(preterm)-610.3(or)-612.7(low)]TJ
0 -1.1116 TD
[(birthweight)-308.4(and)-304(sick)-299.2(babie)-8(s,)-298.1(pass)-304.7(their)-306.4(initial)-303.3(screening)]TJ
0 -1.1174 TD
[(test)-368.5(but)-360.5(are)-368.5(at)-366.4(high)-361.6(risk)-367.2(for)-360.3(later)-365.2(development)-368.4(of)-365(mild)]TJ
0 -1.1116 TD
[(CH.)-318.6(For)-314.1(these)-313(groups,)-315.1(a)-319(postscreening)-317.2(strategy)-316.4(may)-316.7(be)]TJ
T*
[(considered)-342.7(\(1/)]TJ
/F4 1 Tf
5.7943 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 320.8251 583.4266 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 329.6692 582.1227 Tm
-.0158 Tc
[(I)-15.8(n)-645.8(p)-15.8(a)9.6(tien)-15.8(t)10.7(s)-661.8(with)-662(Do)-15.8(w)9.9(ns)-661.8(sy)-15.8(n)10.8(dro)-15.8(m)9.6(e)-.8(,)-658.6(w)-.5(e)-663.1(r).4(e)-15.8(c)8.5(ommend)]TJ
0 -1.1116 TD
[(me)-15.8(a)8.5(s).6(ur)-15.8(i)10.7(n).4(g)-253(T)-.8(SH)-253.9(at)-253.2(th)-15.8(e)-238(e)-15.8(n)9.6(d)-253(of)-253(the)-254.2(n).4(eo)-15.8(n)10.8(a)-.8(tal)-253.2(p).4(e)-15.8(r)9.7(iod)-253(\().4(1)-15.8(/)]TJ
/F4 1 Tf
20.2511 0 TD
-.0163 Tc
(++)Tj
/F3 1 Tf
1.0713 0 TD
0 Tc
[(0\))26.6(.)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 320.8251 561.5432 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 329.6692 560.2393 Tm
[(Th)19.6(e)-273(i)0(n)20.7(i)0(t)14.8(i)0(a)19.5(l)-266.2(sc)14.1(re)19.7(en)19.7(in)20.7(g)-271.8(i)0(n)-261.5(a)0(n)-256.8(a)0(f)14(f)0(e)19.7(c)0(t)19.5(e)0(d)-262.5(t)0(w)19.8(i)0(n)-261.5(m)0(a)18.4(y)-266(be)-262.5(no)20.8(rm)19.6(al)19.5(;)]TJ
0 -1.1174 TD
[(a)-376.6(s)0(t)15.1(r)0(a)19.7(t)0(e)19.6(g)0(y)-365.1(o)0(f)-365(a)-376.6(se)19.9(co)13.9(nd)-365.1(sc)19.9(re)19.7(en)19.7(in)20.7(g)-375.5(s)0(h)15.3(o)0(u)20.8(l)0(d)-365.2(b)0(e)-366.2(c)0(o)19.7(n)0(s)21(i)0(d)15(e)0(r)19.7(e)0(d)19.7(.)]TJ
0 -1.1116 TD
[(Th)19.6(e)-319(n)0(o)20.8(n)0(a)13.9(f)0(f)20.9(e)0(c)18.5(t)0(e)19.6(d)-317.9(si)20.9(bl)20.7(in)15(g)-312.1(o)0(f)-307.4(t)0(w)14.1(i)0(n)20.7(s)-317.7(sh)21(ou)20.8(ld)-307.6(be)-308.6(fo)20.9(ll)20.6(ow)14.2(ed)-302.9(up)]TJ
T*
[(fo)15.1(r)-323.6(p)0(o)20.8(s)0(s)21.2(i)0(b)20.7(l)0(e)-314.5(T)0(S)14(H)-318.7(el)13.8(ev)19.7(at)19.6(io)20.7(n)-323.6(l)0(a)19.5(t)0(e)19.5(r)-323.6(in)-313.4(li)14.8(fe)-314.4(\(2)20.9(/)]TJ
/F4 1 Tf
17.0199 0 TD
(+)Tj
/F3 1 Tf
.5414 0 TD
[(00)20.8(\).)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 320.8251 517.6628 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 329.6692 516.4156 Tm
[(Cl)13.9(in)20.7(ic)19.6(al)-527.6(su)15.3(sp)21(ic)19.6(io)20.7(n)-542.5(o)0(f)-532.1(h)0(y)20.8(p)0(o)20.8(t)0(h)20.7(y)0(r)20.9(o)0(i)14.9(d)0(i)20.7(s)0(m)19.8(,)-539.1(de)19.7(sp)21(it)14.8(e)-537.9(n)0(o)20.8(r)0(m)19.7(a)0(l)]TJ
0 -1.1174 TD
[(TS)14(H)-353.3(i)0(n)-347.9(T)0(S)19.8(H)0(-)20(b)0(a)19.7(s)0(e)14.1(d)-352.4(sc)14.1(re)19.7(en)19.7(in)20.7(g)-358.2(p)0(r)20.9(o)0(g)20.8(r)0(a)19.7(m)0(s)14(,)-354.8(sh)21(ou)20.8(ld)-347.9(pr)20.9(om)19.6(pt)]TJ
0 -1.1116 TD
[(fu)15.1(rt)20.7(he)19.7(r)-156.6(e)0(v)19.7(a)0(l)19.5(u)0(a)19.7(t)0(i)20.6(o)0(n)-146.2(f)0(o)20.9(r)-156.6(pr)20.9(im)19.5(ar)14(y)-150.8(\()0(r)15.1(a)0(r)19.7(e)-152(ca)18.5(se)14.1(s)-150.7(o)0(f)-146.2(f)0(a)19.7(l)0(s)15.1(e)0(-)19.7(n)0(e)19.7(g)0(a)19.7(t)0(i)20.6(v)0(e)]TJ
T*
[(ne)13.9(on)20.8(at)19.5(al)-187.8(sc)19.9(re)19.7(en)19.7(in)15(g)-196.9(r)0(e)19.7(s)0(u)21(l)0(t)20.6(s)0(\))-186.3(a)0(n)13.9(d)-191.2(ce)12.8(nt)20.7(ra)19.7(l)-197.1(C)0(H)18.9(,)-193.5(pa)13.9(rt)20.7(ic)19.5(ul)20.7(ar)19.7(ly)-186.6(in)]TJ
0 -1.1174 TD
[(ch)13.9(il)20.6(dr)20.9(en)-239.5(wi)19.8(th)-244.2(a)-249.9(f)0(a)19.7(m)0(i)19.5(l)0(y)-244.2(h)0(i)20.7(s)0(t)20.9(o)0(r)20.9(y)-248.8(of)-244.1(ce)18.5(nt)20.7(ra)19.7(l)-254.7(C)0(H)-240.2(\()0(2)20.9(/)]TJ
/F4 1 Tf
18.6845 0 TD
(+)Tj
/F3 1 Tf
.5414 0 TD
[(00)20.8(\).)]TJ
/F12 1 Tf
8.9663 0 0 8.9663 320.8251 451.1054 Tm
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 369.9778 451.1054 Tm
-.0174 Tc
[(Babies)-317.8(with)-312.2(pr)4.6(imary)-312.2(C)-2.2(H)-313.1(w)-2.1(h)4.5(o)-312.2(are)-313.4(b)-1.2(o)4.5(r)-1.2(n)-312.2(prema-)]TJ
-6.0074 -1.1174 TD
-.0216 Tc
[(tu)-5.4(r)-5.4(e)-352.2(or)-351(w)-6.3(i)-5.5(th)-351(l)-5.6(o).3(w)-351.9(b)-5.4(i)-5.5(r).4(t)-5.6(h)-5.4(we)-6.6(i)-5.5(g)-5.4(ht)-5.5(,)-347.6(o)-5.4(r)-351(w)-6.3(ho)-351(a)-6.6(r).4(e)-352.2(s)-5.2(i)-5.5(c)-.8(k)-351(i)-5.5(n)-351(t).2(h)-5.4(e)-352.2(ne)-6.6(o)-5.4(n).3(a)-6.6(t)-5.5(al)]TJ
0 -1.1116 TD
-.0158 Tc
[(p)6.1(e)-.8(rio)6.1(d)-189.7(may)-189.7(n)6.1(o).4(t)-189.8(b).4(e)-190.8(a)-.8(b)6.1(l).3(e)-190.9(t).3(o)-189.7(g).4(e)5(n).4(er)6.2(ate)-190.8(a)5(n)-189.7(a)-.8(de)5(qua)5(te)-190.8(TSH)-190.6(r)6.2(espo)6.1(nse)-190.8(i).2(n)]TJ
T*
-.0166 Tc
[(t)5.2(h)-.4(e)-566()-.3(rs)5.5(t)-565(w)-1.3(eeks)-564.7(of)-564.8(li)5.2(fe.)-561.4(T)-1.6(herefo)5.3(re,)-561.4(i)-.6(n)-564.9(T)-1.6(S)5.5(H)-1.3(-based)-564.9(n)5.3(eon)5.3(a)-1.6(tal)]TJ
T*
-.0164 Tc
[(screenin)5.5(g)-190.3(p)-.2(r)5.6(ogr)5.6(ams)5.7(,)-186.9(t)-.4(heir)-190.3(s)5.7(c)-1.4(reenin)5.5(g)-190.3(r)5.6(esul)5.4(t)-190.4(m)4.3(ay)-184.5(be)-185.7(fals)5.7(e)-191.4(n)5.5(egative)]TJ
0 -1.1174 TD
-.0166 Tc
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14.9752 0 TD
0 Tc
[(DY)25.9(R)15(K)15.2(1)16.2(A)]TJ
/F3 1 Tf
3.8763 0 TD
-.016 Tc
[(gene)-294.7(\()-16(4)10.6(04)-16(3)10.6(\)).2(.)]TJ
-18.8515 -1.1116 TD
-.0158 Tc
[(Bec)-15.8(a)8.5(use)-467.3(man)-15.8(y)-450(n)-15.8(e)9.6(onat)-15.8(e)9.5(s)-466(w)-.5(ith)-466.2(Do)-15.8(w)9.9(ns)-466(s)-15.8(y)11(ndr)-15.8(o)10.8(m)-.8(e)-467.3(h).4(ave)-467.3(non)-15.8(-)]TJ
T*
-.0161 Tc
[(th)-16.1(y)10.5(roi)-16.1(d)10.4(a)-1.1(l)-178.6(illn)-16.1(e)9.3(s).3(s)-178.3(due)-179.6(to)-178.5(\()-16.1(s)10.7(urg)-16.1(e)9.3(r).1(y)-178.5(for)-16.1(\))-162.2(c)-16.1(a)8.2(rdi)-16.1(a)9.2(c)-173.9(o)-16.1(r)-162.3(i)-16.1(n)10.4(tes)-16.1(t)10.6(ina)-16.1(l)-163.6(d)-16.1(i)10.4(sea)-16.1(s)9.5(e)]TJ
0 -1.1174 TD
-.0157 Tc
[(\(4)-15.7(4)10.9(\)).5(,)-416.5(T)-.7(S)-15.7(H)-404.5(gen)-15.7(e)9.7(rat)-15.7(i)10.6(on)-420(may)-414.2(be)-421.1(impa)-15.7(i)9.6(r).5(ed)-420(res)-15.7(u)11.1(lti)-15.7(n)10.8(g)-414.2(i)-15.7(n)-403.9(a)-421.1(f).5(als)-15.7(e)9.9(-)]TJ
0 -1.1116 TD
[(neg)-15.7(a)9.7(tiv)-15.7(e)-439.5(n).5(e)-15.7(o)9.7(nata)-15.7(l)-439.6(s)-15.7(c)9.9(r).5(een)-15.7(i)10.8(n).5(g)-454.5(r).5(esu)-15.7(l)10.8(t)-448.9(\()-15.7(i)10.8(n)-454.5(TSH-b)-15.7(a)9.7(sed)-454.5(s).7(cr)-15.7(e)9.8(e)-.7(ni)-15.7(n)10.8(g)]TJ
T*
[(pr)-15.7(o)10.9(gra)-15.7(m)8.5(s).7(\).)-215(Ther)-15.7(e)9.8(for)-15.7(e)9.8(,)-215(addit)-15.7(i)10.6(ona)-15.7(l)-203.5(meas)-15.7(u)11.1(r).5(emen)-15.7(t)-202.3(o).5(f)-212.6(T)-.7(S)-15.7(H)-202.9(and)-212.6(f)-15.7(T)9.7(4)]TJ
0 -1.1174 TD
-.016 Tc
[(ar)-16(o)10.6(und)-264.8(the)-260.2(a)-16(g)9.4(e)-260.2(of)-264.7(3)-259(t).1(o)-264.8(4)-259(wee)-16(k)9.4(s)-258.8(s)-16(h)10.8(oul)-16(d)-248.7(b).2(e)-260.2(c)-16(o)9.4(n).2(si)-16(d)10.5(e)-1(re)-16(d)9.4(.)]TJ
1.0137 -1.1116 TD
0 Tc
[(In)-526.3(babies)-527.2(born)-528.5(into)-528.8(families)-530.9(affected)-531.9(with)-529.7(primary)-528.5(or)]TJ
-1.0137 -1.1116 TD
[(central)-264.9(CH,)-261(fT4)-263.7(and)-257.9(TSH)-264.4(measurements)-267.7(are)-259(advised,)-266.8(even)-260.2(if)]TJ
T*
[(TSH)-811.6(was)-811.5(normal)-809.7(in)-808.7(TSH-based)-814.5(screening)-813.9(programs.)]TJ
0 -1.1174 TD
[(A)-393.6(delayed)-397.2(rise)-391.4(of)-393.8(TSH)-396.9(has)-390.2(been)-398.4(reported)-391.3(in)-394(newborns)-396.5(af-)]TJ
0 -1.1116 TD
[(fected)-206(with)-207.1(defects)-206.9(in)-203.9(the)-200.4(DUOXs)-210.4(system)-204.6(\(16\).)-203.6(In)-203.8(central)-207.3(CH,)]TJ
T*
[(TSH)-442.9(is)-445.6(usually)-446.7(normal,)-444.5(but)-446.9(can)-443.4(be)-446.9(lower)-445.4(than)-443.4(normal)-446.8(or)]TJ
0 -1.1174 TD
[(mildly)-422.9(elevated;)-429.7(only)-419.2(fT4)-424.9(will)-420.4(contribute)-428.4(to)-417(the)-425.1(diagnosis)]TJ
0 -1.1116 TD
[(\(25,45\).)-376.3(In)-376.5(case)-376.3(of)-376.5(a)-376.6(known)-375(genetic)-374.3(cause,)-380.9(\(even)-376.4(prenatal\))]TJ
T*
[(genetic)-282.2(testing)-285.5(can)-282.1(prevent)-280.8(diagnostic)-284.2(delay.)]TJ
1.0137 -1.1174 TD
[(Central)-351.1(CH)-349.7(should)-346.4(be)-348.9(considered)-348.5(in)-347.9(neonates)-352.1(with)-351.1(clini-)]TJ
-1.0137 -1.1116 TD
[(cal)-305.3(manifestations)-314(of)-301.7(CH)-309.4(or)-301.7(congenital)-308.6(hypopituita)-8(rism,)-302.7(but)]TJ
T*
[(a)-635.8(low,)-635.5(normal,)-640.3(or)-635.7(slightly)-636.9(elevated)-635.8(TSH)-638.8(concentration)]TJ
T*
[(\(25,45,46\).)-312.8(In)-313.2(addition,)-307.5(we)-315.3(recommend)-315.3(endocrine)-313(testing)-314.3(in)]TJ
0 -1.1174 TD
[(all)-246.6(neonates)-248.4(with)-247.4(a)-244.2(familial)-249(history)-249.6(of)-244.1(central)-247.6(CH,)-249.5(or)-244.1(signs)-247.2(or)]TJ
0 -1.1116 TD
[(symptoms)-391.2(of)-388.1(congenital)-395(hypopituitarism,)-391.4(for)-389.1(example,)-390.4(mi-)]TJ
T*
[(cropenis)-293.3(with)-293.5(undescended)-298.8(testes,)-294.5(hypoglycemia,)-292.3(prolonged)]TJ
0 -1.1174 TD
[(jaundice,)-286.7(or)-278.6(unexplained)-286.6(failure)-280.9(to)-278.8(thrive.)]TJ
/F6 1 Tf
8.9663 0 0 8.9663 62.022 248.8818 Tm
[(2.)-501.1(DIAGNOSTICS)-310.4(AND)-311.9(CRITERIA)-312.7(FOR)-308.7(TREATMENT)]TJ
/F3 1 Tf
9.843 0 0 9.843 71.8866 231.9306 Tm
[(2.1.)-498.6(Biochemical)-526.3(criteria)-531(used)-523.7(in)-520.7(the)-523(decision)-523.8(to)-520.7(start)]TJ
1.9986 -1.1116 TD
[(treatment)-337.5(for)-337.3(CH)]TJ
-1.9986 -1.1116 TD
[(2.2.)-498.6(Communication)-302.8(of)-301.7(abnormal)-300.5(neonatal)-306.3(screening)-301.3(and)]TJ
1.9986 -1.1174 TD
[(conmatory)-337.1(results)]TJ
-1.9986 -1.1116 TD
[(2.3.)-498.6(Imaging)-338.5(techniques)-337.1(in)-330.6(CH)]TJ
T*
[(2.4.)-498.6(Associated)-337.8(malformations)-341.8(and)-332.8(syndromes)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 62.022 144.2267 Tm
[(2.1.)-502.8(Biochemical)-333.5(criteria)-333.7(used)-336.3(in)-331.6(the)-334.6(decision)]TJ
0 -1.2203 TD
[(to)-336.6(start)-329.9(treatment)-336(for)-337.3(CH)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 101.707 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 100.4031 Tm
[(A)-307.2(newborn)-309.2(with)-310.8(an)-308.6(abnormal)-312(neonatal)-312.1(screening)-312.8(result)]TJ
0 -1.1116 TD
[(should)-334.8(be)-331.7(referred)-340.5(to)-330.6(an)-337.4(expert)-331.6(center)-338.5(\(1/)]TJ
/F4 1 Tf
16.9393 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 79.7669 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 78.463 Tm
[(An)-446.6(abnormal)-444.4(screening)-451(result)-445.5(should)-444.3(be)-446.9(followed)-448.8(by)]TJ
0 -1.1116 TD
[(conrmatory)-378.4(testing)-383.4(consisting)-380.8(of)-376.5(measurement)-387.8(of)-376.5(se-)]TJ
T*
[(rum)-332.8(fT4)-332.8(and)-338.5(TSH)-333.5(\(1/)]TJ
/F4 1 Tf
8.8411 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 726.973 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 725.6691 Tm
[(If)-583.9(the)-586.3(serum)-583.6(fT4)-586.2(concentration)-589.5(is)-583.9(below)-583.6(and)-586.2(TSH)]TJ
0 -1.1116 TD
[(clearly)-408.8(above)-405.3(the)-407.8(age-specic)-409.3(reference)-413(interval,)-406.6(then)]TJ
T*
[(LT4)-334(treatment)-337.5(should)-334.8(be)-337.4(started)-332.6(immediately)-341.1(\(1/)]TJ
/F4 1 Tf
19.9747 0 TD
(+++)Tj
/F3 1 Tf
1.653 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 694.0912 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 692.7872 Tm
[(If)-422.6(the)-425.1(serum)-428.1(TSH)-419.9(concentration)-434(is)]TJ
/F4 1 Tf
14.9061 0 TD
(>)Tj
/F3 1 Tf
.5529 0 TD
[(20)-163.5(mU/L)-428.3(at)-424(con-)]TJ
-15.4591 -1.1116 TD
[(rmatory)-304.9(testing)-297.1(\(approximately)-308.5(in)-296.1(the)-298.3(second)-302.5(week)-301.3(of)]TJ
T*
[(life\),)-298.3(treatment)-297.2(should)-288.8(be)-297.1(started,)-295.7(even)-294.7(if)-290.3(fT4)-298.2(is)-290.1(normal)]TJ
0 -1.1174 TD
[(\(arbitrary)-336(threshold,)-337.1(expert)-337.3(opinion\))-337.3(\(2/)]TJ
/F4 1 Tf
16.1272 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 650.2676 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 648.9636 Tm
[(If)-278.6(the)-275.3(serum)-278.4(TSH)-281.7(concentration)-278.5(620)-171.4(mU/L)-278.5(beyond)-278.5(the)]TJ
0 -1.1116 TD
[(age)-368.5(of)-370.8(21)-365.1(days)-368.2(in)-370.9(a)-365.1(healthy)-373.2(neonate)-368.4(with)-368.4(an)-372(fT4)-367.3(con-)]TJ
T*
[(centration)-262.5(within)-255.5(the)-258(age-specic)-265.3(reference)-263.3(interval,)-256.8(we)]TJ
0 -1.1174 TD
[(suggest)-371.5(to)-365.2(either)-366.3(start)-369.6(LT4)-368.6(treatment)-366.3(immediately)-375.7(and)]TJ
0 -1.1116 TD
[(retest,)-496.2(off-treatment,)-495(at)-498.8(a)-491.8(later)-491.9(stage,)-495(or)-491.7(to)-491.9(withhold)]TJ
T*
[(treatment)-239.6(but)-233.8(retest)-239.4(1)-231.5(t)0(o)-238.5(2)-231.5(weeks)-238.9(later)-238.4(and)-234.9(to)-232.7(re-evaluate)]TJ
0 -1.1174 TD
[(the)-459.6(need)-461.7(for)-464(treatment)-464.3(\(lack)-457.2(of)-462.9(evidence)-462.9(in)-457.3(favor)-461.6(or)]TJ
0 -1.1116 TD
[(against)-407.5(treatment,)-404.3(this)-401.9(is)-405.3(an)-400.8(area)-405.3(of)-405.3(further)-406.3(investiga-)]TJ
T*
[(tion\))-334(\(2/)]TJ
/F4 1 Tf
3.3464 0 TD
(++)Tj
/F3 1 Tf
1.1001 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 551.6219 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 550.318 Tm
[(In)-301.7(countries)-300.3(or)-295.9(regions)-302.5(where)-302.4(thyroid)-295.9(function)-303.9(tests)-300.3(are)]TJ
0 -1.1116 TD
[(not)-251.1(readily)-246.4(available,)-254.5(LT4)-247.6(treatment)-251.1(should)-248.5(be)-251(started)-246.2(if)]TJ
T*
[(lter)-548.1(paper)-549.2(TSH)-546.6(concentration)-549.2(is)]TJ
/F4 1 Tf
14.8773 0 TD
(>)Tj
/F3 1 Tf
.5529 0 TD
[(40)-163.5(mU/L)-549.3(\(at)-551.7(the)]TJ
-15.4303 -1.1174 TD
[(moment)-661.2(of)-653(neonatal)-657.7(screening;)-665.4(arbitrary)-657.5(threshold,)]TJ
0 -1.1116 TD
[(expert)-337.3(opinion\))-331.6(\(2/)]TJ
/F4 1 Tf
7.6892 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 496.8566 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 495.5526 Tm
[(If)-434.1(the)-430.8(serum)-433.9(fT4)-430.7(is)-428.3(low,)-434(and)-430.7(TSH)-431.4(is)-434.1(low,)-434(normal)-429.6(or)]TJ
0 -1.1116 TD
[(slightly)-429.6(elevated,)-437.6(the)-430.8(diagnosis)-431.4(central)-437.6(CH)-430.3(should)-427(be)]TJ
0 -1.1174 TD
[(considered)-337(\(1/)]TJ
/F4 1 Tf
5.7943 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 463.9747 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 462.6707 Tm
[(In)-434.1(neonates)-432.7(with)-437.5(central)-431.9(CH,)-433.8(we)-436.2(recommend)-436.3(to)-434.3(start)]TJ
0 -1.1116 TD
[(LT4)-518.3(treatment)-521.8(only)-517.2(after)-514.8(evide)-8(nce)-512.5(of)-520.5(intact)-516.2(adrenal)]TJ
0 -1.1174 TD
[(function;)-639.2(if)-641.6(coexistent)-636.7(central)-645(adrenal)-639.1(insufciency)]TJ
0 -1.1116 TD
[(cannot)-239.5(be)-233.8(ruled)-231.4(out,)-237.3(LT4)-236.1(treatment)-233.9(must)-236(be)-233.8(preceded)-238.1(by)]TJ
T*
[(glucocorticoid)-388(treatment)-383.6(to)-382.5(prevent)-384.5(possible)-384.2(induction)]TJ
0 -1.1174 TD
[(of)-336.2(an)-331.7(adrenal)-339.6(crisis)-335.9(\(2/)]TJ
/F4 1 Tf
9.3019 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F12 1 Tf
8.9663 0 0 8.9663 323.0361 385.3416 Tm
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 372.2456 385.3416 Tm
[(Early)-342(detection)-347.9(and)-344.3(prompt)-342(treatment)-343.3(of)-342(CH)]TJ
-6.0131 -1.1116 TD
[(\(withi)-7.8(n)-260.3(the)-263.8(rst)-263.3(2)-260.3(weeks)-267.7(of)-261.4(life\))-266(are)-264.8(essential)-266.8(to)-261.5(optimize)-266.2(the)]TJ
0 -1.1174 TD
[(neurocognit)-8.9(ive)-390.5(outcome,)-389.2(linear)-395.1(growth,)-391.2(the)-390.5(onset)-392.5(and)-390.4(pro-)]TJ
0 -1.1116 TD
[(gression)-309.2(of)-307.4(puberty,)-306.2(pubertal)-310.9(growth,)-304.8(and)-309.7(nal)-305(height)-307.5(of)-301.7(af-)]TJ
T*
[(fected)-678.3(neonates)-680.4(\(47\).)-675.9(All)-672.6(newborns)-678.8(with)-673.7(an)-677.2(abnormal)]TJ
0 -1.1174 TD
[(neona)-7.8(tal)-223.6(screening)-232.2(result)-226.7(must)-230.2(be)-228(referred)-231(to)-227(an)-228(expert)-227.9(center)]TJ
0 -1.1116 TD
[(for)-469.8(immediate)-471.3(thyroid)-468.7(function)-465.2(testing)-469.8(\(TSH)-467.1(and)-465.2(fT4\))-466.3(to)]TJ
T*
[(conrm)-285.3(the)-281.1(diagnosis)-281.7(of)-284.4(CH.)]TJ
1.0137 -1.1116 TD
[(Treatment)-315.6(is)-307.4(indicated)-313.3(if)-313.3(the)-309.9(serum)-312.9(TSH)-310.5(concentration)-313.1(is)]TJ
/F4 1 Tf
-1.0137 -1.1174 TD
(>)Tj
/F3 1 Tf
.5529 0 TD
[(20)-169.2(mU/L)-244(or)-244.1(fT4)-246.4(is)-244(below)-243.8(the)-246.5(age-specic)-248.1(reference)-246(interval)]TJ
-.5529 -1.1116 TD
[(\(48\).)-249.7(In)-244.1(the)-240.7(latter)-245.4(case,)-247.3(severe,)-249.4(moderate,)-247.5(and)-246.4(mild)-242(forms)-248.4(can)]TJ
T*
[(be)-291.3(classied)-295.3(according)-295.7(to)-290.3(fT4)-292.4(concentrations,)]TJ
/F4 1 Tf
18.7133 0 TD
(<)Tj
/F3 1 Tf
.5529 0 TD
[(5,)-292.5(510,)-290.1(and)]TJ
-19.2662 -1.1174 TD
[(1015)-172.5(pmol/L,)-277.7(respectively)-288.7(\(1\).)]TJ
1.0137 -1.1116 TD
[(Whether)-334.9(neonates)-340.5(with)-333.8(mild)-328.4(hypothyroidism/hyperth)-9.8(yro-)]TJ
-1.0137 -1.1116 TD
[(tropin)-6.8(emia)-399.7(\(i.e.,)-406.5(diagnostic)-405.2(TSH)-402.6(concentrations)-411.9(between)-403.9(6)]TJ
0 -1.1174 TD
[(and)-321.2(20)-163.5(mU/L,)-322.3(but)-314.5(a)-319(normal)-314.4(fT4)-321.2(concentration\))-319.9(benet)-319.9(from)]TJ
0 -1.1116 TD
[(LT4)-190(treatment)-193.5(is)-186.4(still)-190.1(unclear)-189.8(\(49,50\).)-186.2(Randomized)-195.5(controlled)]TJ
T*
[(trials)-267.1(addressing)-266.5(this)-263.7(question)-263.5(have)-260.2(not)-262.6(been)-265.9(performed.)-264.5(The)]TJ
0 -1.1174 TD
[(evolution)-408.9(of)-399.6(the)-407.8(TSH)-402.6(and)-401.9(fT4)-401.9(concentrations)-411.9(and)-401.9(trend)-404.2(is)]TJ
0 -1.1116 TD
[(instrumenta)-10.1(l)-329.5(i)0(n)-330.6(deciding)-333.9(whether)-333.6(to)-330.6(treat)-330.6(or)-336.2(not;)-327.2(the)-332.9(family)]TJ
T*
[(history,)-362.5(thyroid)-353.5(imaging,)-359.4(and,)-353.5(if)-359.4(available,)-358.2(genetic)-357(analysis)]TJ
T*
[(may)-305.2(be)-297.1(helpful)-302.8(in)-301.8(predicting)-301.7(the)-304.1(course)-302.4(of)-295.9(the)-304.1(thyroid)-301.7(func-)]TJ
0 -1.1174 TD
[(tion.)-307.6(In)-307.4(a)-301.8(large)-307.4(cohort)-307.4(study,)-308.4(Lain)]TJ
/F5 1 Tf
14.0652 0 TD
[(et)-303(al.)]TJ
/F3 1 Tf
2.3672 0 TD
[(found)-305(a)-307.5(worse)-306.8(neu-)]TJ
-16.4324 -1.1116 TD
[(rocognitive)-274(outcome)-276.3(in)-267.3(children)-270.5(of)-272.9(school)-266.9(age)-270.6(with)-276.2(neonatal)]TJ
T*
[(screening)-347.4(TSH)-339.3(concentrations)-342.8(between)-346.3(the)-338.7(75th)-338.6(and)-338.5(99.9th)]TJ
0 -1.1174 TD
[(perce)-9(ntiles)-203.8(\(51\),)-209.4(while)-203.6(those)-208.2(with)-207.1(neonatal)-208.4(TSH)-206.8(values)-210.5(above)]TJ
0 -1.1116 TD
[(the)-298.3(99.9th)-297.1(percentile)-304(\(1214)-167.9(mU/L\))-296.9(had)-298.2(better)-297.1(cognitive)-294.9(de-)]TJ
T*
[(velopment,)-334(possibly)-331.2(due)-332.8(to)-330.6(LT4)-328.2(treatment.)-335.2(In)-330.5(contrast,)-331.4(in)-330.6(a)]TJ
0 -1.1174 TD
[(Belgi)-8(an)-193.4(cohort)-203.7(of)-198(children,)-199.1(there)-198(was)-201(no)-198(relationship)-200.1(between)]TJ
0 -1.1116 TD
[(mild)-374.5(neonatal)-375.4(TSH)-368.1(elevation)-376.7(and)-367.3(neurodevelo)-9.9(pment)-370.9(at)-372.1(the)]TJ
T*
[(preschool)-288.6(age)-282.1(\(5254\).)]TJ
/F6 1 Tf
8.9663 0 0 8.9663 62.022 749.6502 Tm
(394)Tj
40.9535 0 TD
[(VAN)-332.3(TROTSENBURG)-337.1(ET)-338.7(AL.)]TJ
ET
endstream
endobj
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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[(started)-286.5(\(45\).)]TJ
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()Tj
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T*
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T*
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(00\).)Tj
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[(A)-485.8(conrmed)-484.5(CH)-482.2(diagnosis)-483.2(should)-484.6(be)-481.4(communicated)]TJ
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/F12 1 Tf
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(Evidence.)Tj
/F3 1 Tf
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T*
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T*
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T*
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T*
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T*
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T*
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(Summary)Tj
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(++)Tj
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(0\).)Tj
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()Tj
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[(We)-518.2(recommend)-516.9(imaging)-517.2(of)-509(the)-517.2(thyroid)-514.8(gland)-513.7(using)]TJ
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[(either)-671.5(radioisotope)-666.6(scanning)-667.7(\(scintigraphy\))-668.7(with)-667.9(or)]TJ
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(\(1/)Tj
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(0\).)Tj
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/F3 1 Tf
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(00\).)Tj
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(Evidence.)Tj
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[(of)-261.4(diagnosis.)-262.1(However,)-262.9(this)-263.7(approach)-259.9(should)-260(never)-267(delay)-261.4(the)]TJ
T*
[(start)-260.1(of)-261.4(treatment)-262.7(in)-261.5(newborns)-264.1(with)-259(CH.)-266.7(Early)-261.4(determination)]TJ
T*
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[(nosis)-368.1(\(including)-375.4(visual)-370.7(evidence\))-371.8(and,)-370.8(with)-374.2(that,)-366.4(strong)-375.1(ar-)]TJ
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[(guments)-897(that)-898.6(their)-899.6(child)-899.7(has)-897(a)-900.8(congenital)-896.1(disorder)]TJ
T*
[(necessitating)-289.8(lifelong)-281(daily)-283.4(treatment.)-289.1(Furthermore,)-289.7(an)-279.8(early)]TJ
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[(accurate)-417.9(diagnosisin)-412.9(most)-414.5(cases)-411.8(achievable)-420.3(by)-411.1(dual)-414.6(im-)]TJ
0 -1.1116 TD
[(agingabolishes)-297.6(the)-298.3(need)-294.7(for)-297(further)-296.9(diagnostic)-295.8(testing)-297.1(and)]TJ
T*
[(re-evaluation)-364.9(of)-359.3(the)-361.7(cause)-360.1(later)-359.4(on.)-362.7(Finally,)-358.1(\(dual\))-364.9(imaging)]TJ
0 -1.1174 TD
[(can)-437.6(give)-443.4(direction)-444.6(to)-440.1(genetic)-443.4(counseling)-439.6(and)-442.2(testing,)-444.5(pro-)]TJ
0 -1.1116 TD
[(viding)-196.9(information)-199.1(about)-202.6(the)-194.7(risk)-200.1(of)-198(recurrence)-206.8(and)-194.5(a)-203.8(possible)]TJ
T*
[(early)-278.6(diagnosis)-287.4(in)-278.8(future)-284.3(siblings.)]TJ
/F5 1 Tf
1.0137 -1.8949 TD
[(Thyroid)-337(US.)]TJ
/F3 1 Tf
5.3047 0 TD
[(US)-285.1(is)-284.4(an)-279.8(important)-289.1(diagnostic)-284.2(tool)-286.9(for)-279.7(deter-)]TJ
-6.3184 -1.1174 TD
[(mining)-278.8(the)-281.1(presence)-283.9(of)-278.6(the)-281.1(thyroid)-278.6(gland)-277.5(and,)-278.6(when)-282.9(present,)]TJ
0 -1.1116 TD
[(its)-337.4(location,)-343.3(size,)-338.4(and)-338.5(echotexture.)-343(US,)-340.4(however,)-336.9(is)-342(less)-339.4(ac-)]TJ
T*
[(curate)-471(than)-472.2(radionuclide)-472.1(scan)-473.1(for)-469.8(detection)-474.6(of)-468.7(an)-475.7(ectopic)]TJ
0 -1.1174 TD
[(thyroid)-670.3(gland.)-678.4(It)-670.4(is)-670.3(a)-676.1(noninvasive)-676.9(nonirradiating)-674.8(cost-)]TJ
0 -1.1116 TD
[(effective)-279.7(imaging)-275.3(technique,)-282(but)-274.1(highly)-277.6(observer)-281.6(dependent.)]TJ
T*
[(Thyroid)-556.2(volume)-550.5(in)-555.3(newborns)-557.8(varies)-556(from)-552.7(0.84)]TJ
/F4 1 Tf
20.4873 0 TD
()Tj
/F3 1 Tf
.72 0 TD
[(0.38)-553.9(to)]TJ
-21.2072 -1.1174 TD
(1.62)Tj
/F4 1 Tf
1.918 0 TD
()Tj
/F3 1 Tf
.7142 0 TD
[(0.41)-168(mL)-373.2(\(6062\),)-368.2(without)-366.1(signicant)-376.2(changes)-368.1(during)]TJ
-2.6322 -1.1116 TD
[(the)-281.1(rst)-286.4(3)-277.6(weeks)-285(of)-284.4(life)-282.3(\(63\).)-284.2(Thyroid)-285.5(size)-283.1(can)-282.1(be)-285.6(inuenced)]TJ
T*
[(by)-405.4(\(long-term\))-406.3(TSH)-402.6(suppre)-7.5(ssion)-402.7(during)-404.1(LT4)-408.9(treatment.)-410.1(In)]TJ
0 -1.1174 TD
[(that)-288.1(case,)-299.1(TSH)-287.4(should)-294.5(be)-291.4(measured)-295.5(at)-291.5(the)-292.6(time)-289.3(of)-295.9(the)-286.8(US)-296.7(so)]TJ
0 -1.1116 TD
[(that)-414.8(thyroid)-411.1(size)-415.6(can)-414.6(be)-412.3(correctly)-416.8(interpreted.)-416.8(Thyroid)-417.9(US)]TJ
T*
[(should)-277.2(be)-285.6(performed)-284.1(by)-278.7(an)-279.8(expert.)]TJ
/F5 1 Tf
1.0137 -1.8949 TD
[(Thyroid)-411.8(scintigraphy.)]TJ
/F3 1 Tf
9.2443 0 TD
.0115 Tc
[(Scin)4.6(tig)4.6(raph)4.6(y)-358.2(i)4.5(s)-358(t)-1.2(h)4.6(e)-359.4(mos)4.8(t)-358.3(accur)4.7(a)-2.3(te)]TJ
-10.258 -1.1174 TD
.0122 Tc
[(d)5.3(i)-.5(agno)5.3(st)5.2(ic)-393.2(test)-392.2(fo)5.3(r)-392(d)-.4(et)5.2(er)5.4(mi)5.2(ni)5.2(ng)-392.1(th)5.3(e)-393.2(e)-1.6(t)5.2(i)-.5(ol)5.2(og)5.3(y)-397.8(o)5.3(f)-392(C)-1.4(H,)-394.4(es)5.5(pe-)]TJ
0 -1.1116 TD
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[(c)5(i).3(a)5(lly)-293.4(i)6(n)-293.4(ca)5(se)-294.5(of)-293.3(T)5(D)-.5(.)-295.7(T)5(ec)5(hn)6.1(et)6(iu)6.1(m-)6.2(99m)-288.8(\()]TJ
7.3823 0 0 6.5614 473.4424 247.2377 Tm
.0145 Tc
(99m)Tj
9.843 0 0 9.843 486.9353 242.8724 Tm
.0118 Tc
[(Tc\))-294.5(a)3.8(nd)-294.6(io)4.9(di)4.8(ne-)]TJ
-17.8896 -1.1116 TD
.0069 Tc
[(12)-5.7(3)-737.2(\()]TJ
7.3823 0 0 6.5614 336.5291 236.296 Tm
.0145 Tc
(123)Tj
9.843 0 0 9.843 347.9243 231.9306 Tm
.0123 Tc
[(I)5.5(\))-737.5(are)-733(b)5.4(oth)-731.8(c)4.3(ap)5.4(tur)5.5(e)-1.5(d)-731.8(b)-.3(y)-731.8(s)5.6(odi)5.3(um)-733(\()5.5(N)-1.2(a\)-i)5.3(od)5.4(id)5.4(e)]TJ
-3.7668 -1.1174 TD
.0119 Tc
[(s)5.2(y)-.7(mpor)5.1(ter)-236.8(\()5.1(NIS)5.2(\))-236.8(at)-237(t)4.9(h)-.7(e)-238(b)5(as)5.2(al)-231.2(sid)5(e)-238(o)5(f)-236.8(t)4.9(hyr)5.1(ocyt)4.9(es)-236.7(and)-231.1(a)-1.9(r)5.1(e)-238(b)5(o)-.7(t)4.9(h)]TJ
0 -1.1116 TD
.0127 Tc
[(s)6(u).1(it)5.7(ab)5.8(le)-335.1(for)-333.9(imag)5.8(in)5.8(g.)]TJ
7.3823 0 0 6.5614 399.855 214.3559 Tm
.0145 Tc
(99m)Tj
9.843 0 0 9.843 413.3479 209.9905 Tm
.0074 Tc
[(Tc)-346.2(is)-344.8(mo)-5.2(r)-5.2(e)-340.4(w)-6.1(i).4(d)-5.2(e)-.6(l)-5.3(y)-339.3(a)-6.4(v)-5.2(ai)-5.3(la)-6.4(bl)-5.3(e,)-347.4(le)-6.4(ss)]TJ
-10.4135 -1.1116 TD
[(ex)-5.3(pe)-6.5(ns)-5.1(i)-5.4(v).4(e)-6.5(,)-243.8(f)-5.3(a)-6.5(st)-5.4(er)-247.2(i)-5.4(n)-247.2(us)-5.1(e)-248.4(\()-5.3(im)-6.5(ag)-5.3(e)-248.4(a)-.7(c)-6.5(q).4(u)-5.3(i).3(s)-5.1(i)-5.4(ti)-5.4(on)-247.2(1)-5.3(5)-247.2(mi)-5.4(nu)-5.3(t)-5.4(e)-.7(s)-247(a)-6.5(ft)-5.4(er)]TJ
0 -1.1174 TD
.0118 Tc
[(admin)4.9(i)-.9(st)4.8(rati)4.8(on\))5(,)-262.3(a)-2(nd)-260(has)-265.6(a)-266.9(s)5.1(hor)5(ter)-265.7(h)-.8(alf)5(-)-.8(l)4.8(i)-.9(ve)-261.2(th)4.9(an)]TJ
7.3823 0 0 6.5614 505.9841 192.4724 Tm
.0145 Tc
(123)Tj
9.843 0 0 9.843 517.3794 188.0503 Tm
.0068 Tc
(I.)Tj
7.3823 0 0 6.5614 525.8833 192.4724 Tm
.0145 Tc
(99m)Tj
9.843 0 0 9.843 539.3762 188.0503 Tm
.0138 Tc
(Tc)Tj
-23.2174 -1.1116 TD
.0124 Tc
[(i)5.4(s)-316.8(no)5.5(t)-317.1(o)-.2(r)5.6(g)-.2(ani)5.7(ed)5.5(,)-319.3(i)5.4(t)-317.1(i)5.4(s,)-313.6(therefo)5.5(r)-.2(e,)-313.6(d)5.5(i)-.3(f)5.7(cu)5.5(lt)-317.1(t)5.4(o)-317(pr)5.6(ov)5.5(id)5.5(e)-318.2(q)-.2(u)5.5(a)-1.4(n)5.5(-)]TJ
T*
.0069 Tc
[(ti)-5.8()-5.6(c)-1.1(a)-6.9(t)-.1(i)-5.8(o)0(n)-190(o)-5.7(f)-190(t)-5.8(he)-191.2(r)-5.7(a)-6.9(di)-5.8(on)-5.7(uc)-6.9(l)-5.8(i)-.1(d)-5.7(e)-191.2(up)-5.7(ta)-6.9(k)-5.7(e)-191.2(us)-5.5(in)-5.7(g)]TJ
7.3823 0 0 6.5614 478.1479 170.5323 Tm
.0145 Tc
(99m)Tj
9.843 0 0 9.843 491.6408 166.1669 Tm
.0112 Tc
[(Tc.)-188.1(I)4.4(mages)-185.5(a)-2.6(re)]TJ
-18.3677 -1.1116 TD
.0121 Tc
[(o)5.2(f)-202.1(lo)5.2(wer)-196.3(quali)5.1(ty)-202.1(t)5.1(h)-.5(an)-202.1(wi)5.1(th)]TJ
7.3823 0 0 6.5614 415.729 159.5905 Tm
.0145 Tc
(123)Tj
9.843 0 0 9.843 427.1243 155.2252 Tm
.0098 Tc
[(I.)-201(The)-205.6(l)-2.9(atte)-4(r)-204.4(i)2.8(sotope)-205.6(nee)-4(d)2.9(s)-204.2(l)-3(ater)]TJ
-11.8132 -1.1174 TD
.0122 Tc
[(i)5.2(m)-1.6(age)-185.9(a)4.2(cq)5.3(uis)5.5(i)-.5(t)5.2(i)-.5(o)5.3(n)-.4(s)-184.5(\()-.4(at)-184.9(23)5.3(,)-187.1(a)4.2(nd)-184.7(2)5.3(4)-184.7(hou)5.3(rs)5.5(\),)-187.1(b)5.3(u)-.4(t)-184.9(p)5.3(rov)5.3(id)5.3(es)-184.5(more)]TJ
0 -1.1116 TD
[(con)5.2(t)-.6(rast)-254.1(and)-248.2(a)-1.7(dd)5.2(s)-253.7(i)-.6(n)5.2(f)-.5(o)5.2(r)-.5(mat)5.1(i)-.6(on)-248.2(ab)5.2(ou)5.2(t)-254.1(o)-.5(r)5.3(g)-.5(an)5.2(i)5.4(cati)5.1(on)-253.9(p)5.2(roces)5.4(s,)]TJ
T*
.0125 Tc
[(all)5.5(o)-.1(wi)5.5(ng)-322.7(p)5.6(e)-1.3(r)5.7(c)-1.3(h)5.6(l)-.2(or)5.7(at)5.5(e)-323.8(d)-.1(i)5.5(s).1(ch)5.6(ar)5.7(ge)-323.8(test)5.5(in)5.6(g)-322.7(w)-1(hen)-322.7(t)-.2(h)5.6(e)-323.8(th)5.7(yro)5.6(id)-322.7(i)5.5(s)]TJ
0 -1.1174 TD
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[(eut)4.6(opi)4.6(c)-301.7(\(64)4.7(,65)4.7(\))-1(.)-302.8(F)-.9(u)4.7(r)-1(t)4.6(h)-1(ermore,)-302.8(i)-1.1(t)-300.7(e)-2.2(x)4.7(p)-1(o)4.7(s)-.8(es)-300.3(in)4.7(fant)4.6(s)-306.1(t)4.6(o)-306.3(a)-301.7(lo)4.7(wer)]TJ
0 -1.1116 TD
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[(do)-5.4(s)-5.2(e)-231.2(o)-5.4(f)-230(w)-6.3(h)-5.4(ol)-5.5(e-)-5.4(bo)-5.4(dy)-235.8(i)-5.5(r).4(r)-5.4(a)-.8(d)-5.4(i)-5.5(at)-5.5(io)-5.4(n)-230(t)-5.5(h)-5.4(a)-.8(n)]TJ
7.3823 0 0 6.5614 456.8314 104.7685 Tm
.0145 Tc
(99m)Tj
9.843 0 0 9.843 470.2676 100.4031 Tm
.0129 Tc
[(Tc)-225.5(\(3)6(10)]TJ
/F14 1 Tf
3.8648 0 TD
0 Tc
(l)Tj
/F3 1 Tf
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[(Ci/kg)-232.2(v)3.9(s.)]TJ
-20.6255 -1.1116 TD
.0069 Tc
[(50)-5.7(2)-5.7(5)-5.7(0)]TJ
/F14 1 Tf
3.2254 0 TD
0 Tc
(l)Tj
/F3 1 Tf
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[(Ci)-5.3(/k)-5.2(g)-281.7(b)-5.2(od)-5.2(y)-281.7(w)-.3(e)-6.4(i)-5.3(gh)-5.2(t\))-281.7(\()-5.2(6)-5.2(6).5(,6)-5.2(7\))-5.2(.)]TJ
-2.7762 -1.1174 TD
0 Tc
[(When)-318.9(the)-327.1(thyroid)-324.7(is)-318.9(present)-326.7(and)-327(normally)-322.5(located,)-325.9(and)-327(if)]TJ
-1.0137 -1.1116 TD
[(sodium)-203.6(perchlorate)-212.8(is)-203.7(available,)-208.5(perchlorate)-212.8(discharge)-203.4(testing)]TJ
T*
[(can)-207.2(be)-210.7(performed)-215(to)-209.7(study)-207(the)-211.9(iodine)-209.6(retention)-214.2(capacity)-215.3(of)-209.5(the)]TJ
/F6 1 Tf
8.9663 0 0 8.9663 59.7543 749.7069 Tm
[(GUIDELINES)-340.4(FOR)-334(CONGENITAL)-339.9(HYPOTHYROIDISM)-28059.1(395)]TJ
ET
endstream
endobj
152 0 obj
<>stream
/GS1 gs
BT
/F3 1 Tf
9.843 0 0 9.843 62.022 725.1588 Tm
0 0 0 rg
0 Tc
0 Tw
[(thyroid)-221(gland.)-217.6(Sodium)-220.9(perchlorate)-224.3(is)-221(administred)-217.4(and)-223.3(thyroid)]TJ
0 -1.1174 TD
[(activity)-351.5(is)-353.5(measured)-353.1(before)-348.7(and)-350(1)-352.4(hour)-350(afterward.)-351.8(The)-351.2(per-)]TJ
0 -1.1116 TD
[(chlorate)-237.2(discharge)-232.2(test)-230.3(is)-232.5(considered)-233.3(positive)-234.8(when)-231.1(discharge)]TJ
T*
(of)Tj
7.3823 0 0 6.5614 72.9071 696.6423 Tm
(123)Tj
9.843 0 0 9.843 84.0189 692.277 Tm
[(I)-277.5(i)0(s)-272.8(more)-277.5(than)-276.4(10%)-275.1(of)-272.9(the)-275.3(administered)-283.1(dose.)-273.8(Together)]TJ
-2.2348 -1.1116 TD
[(with)-293.5(serum)-295.7(thyroglobulin)-291.3(measurement,)-299(the)-292.6(perchlorate)-293.4(dis-)]TJ
0 -1.1174 TD
[(charge)-326.8(test)-328.2(provides)-326.7(useful)-324.5(information)-325.9(for)-325.8(targeted)-329.3(genetic)]TJ
0 -1.1116 TD
[(testing)-314.3(to)-307.6(diagnose)-310.6(the)-309.9(various)-314(forms)-311.7(of)-307.4(CH)-309.4(caused)-315.2(by)-307.5(dys-)]TJ
T*
[(hormonogenesis)-416.1(\(1\).)-404.1(One)-414.3(pitfall)-412.5(of)-405.3(scintigraphy)-413.1(is)-411.1(lack)-410(of)]TJ
0 -1.1174 TD
[(isotope)-193.2(uptake)-187.6(despite)-194.4(the)-188.9(presence)-191.8(of)-186.5(thyroi)-6.8(d)-185.4(tissue.)-189.6(This)-189.8(can)]TJ
0 -1.1116 TD
[(be)-377.7(due)-373.1(to)-370.9(TSH)-379.6(suppression)-375.7(at)-372.1(the)-379(time)-375.7(of)-370.8(the)-379(scintigraphy)]TJ
T*
[(\(when)-335.8(performed)-341.7(beyond)-336.1(5)-335.2(t)0(o)-336.4(7)-335.2(days)-333.7(after)-336.2(the)-338.7(start)-335(of)-336.2(LT4)]TJ
0 -1.1174 TD
[(treatment\),)-198(previous)-199.9(iodine)-192.3(exposure,)-198.7(maternal)-198.1(blocking)-194.5(TSH)]TJ
0 -1.1116 TD
[(receptor)-300.4(antibodies,)-299.2(and)-298.2(mutations)-294.7(in)-296.1(genes)-301.4(affecting)-301.6(iodine)]TJ
T*
[(uptake)-227.9(\()]TJ
/F5 1 Tf
3.237 0 TD
(NIS)Tj
/F3 1 Tf
1.4975 0 TD
[(\))-225.7(o)0(r)-226.8(TSH)-229.8(receptor)-225.5(\()]TJ
/F5 1 Tf
7.5798 0 TD
(TSHR)Tj
/F3 1 Tf
2.3903 0 TD
[(\))-225.7(defects.)-227.6(In)-226.8(these)-226.6(cases,)]TJ
-14.7045 -1.1116 TD
[(thyroid)-238.3(US)-239.1(should)-242.7(be)-233.7(performed)-243.8(to)-238.5(demonstrate)-241.5(the)-240.7(presence)]TJ
0 -1.1174 TD
[(or)-411.1(absence)-409.6(of)-411.1(thyroid)-411.1(tissue.)-408.5(When)-411(treatment-)-10.3(related)-408.8(TSH)]TJ
0 -1.1116 TD
[(suppression)-214.4(is)-203.7(the)-211.9(cause,)-213.8(and)-206.1(treatment)-210.8(cannot)-210.7(be)-210.7(interrupted,)]TJ
T*
[(thyroid)-428.4(scintigraphy)-424.6(and)-430.7(perchlorate)-425.9(discharge)-433.8(testing)-423.8(can)]TJ
0 -1.1174 TD
[(also)-368.4(be)-366.2(performed)-370.5(after)-365(recombinant)-374.2(human)-365(TSH)-368.1(adminis-)]TJ
0 -1.1116 TD
[(tration)-285.7(\(68\).)]TJ
/F5 1 Tf
1.0137 -1.8373 TD
[(Dual)-385.6(imaging.)]TJ
/F3 1 Tf
6.3011 0 TD
[(The)-334(combination)-338.6(of)-330.5(thyroid)-336.2(US)-331.2(and)-332.8(scin-)]TJ
-7.3148 -1.1116 TD
[(tigraphy)-718.6(provides)-712.6(high-resolution)-720.6(anatomical)-720(\(US\))-713.5(and)]TJ
T*
[(functional)-186.5(\(scintigraphy\))-190.6(information,)-185.3(allowing)-184(to)-180.9(distinguish)]TJ
0 -1.1174 TD
[(between)-455.7(permanent)-458.2(and)-453.7(possible)-453.3(transient)-461.7(CH)-453.4(\(64,67,69\).)]TJ
0 -1.1116 TD
[(Each)-186.5(technique)-192.2(compensates)-190.5(for)-181.8(limitations)-187.9(and)-188.8(pitfalls)-183.1(of)-186.5(the)]TJ
T*
[(other.)-396.1(Dual)-392.5(imaging)-390.5(is)-393.8(particularly)-391.5(effective)-400.7(in)-388.2(conrming)]TJ
0 -1.1174 TD
[(athyreosis)-295.4(\(when)-295.5(scintigraphy)-292.2(shows)-294(absence)-294.4(of)-295.9(isotope)-291.2(up-)]TJ
0 -1.1116 TD
[(take\))-284.4(and)-280.9(detecting)-284.5(thyroid)-278.6(ectopy)-285.5(\(65,67\).)]TJ
/F5 1 Tf
1.0137 -1.8373 TD
[(X-ray)-318.7(of)-319.1(the)-321.4(knee.)]TJ
/F3 1 Tf
7.6604 0 TD
[(At)-268.1(birth,)-268.4(bone)-264.8(maturation)-268.4(is)-267.1(delayed)-270.5(in)]TJ
-8.6741 -1.1116 TD
[(the)-309.9(majority)-305.3(of)-307.4(patients)-310.8(with)-305(severe)-309.4(CH)-309.4(and)-309.7(is)-301.6(considered)-313.9(a)]TJ
T*
[(disease)-402.6(severity)-402.8(parameter.)-405.2(It)-399.7(has)-401.7(been)-404.1(shown)-397.8(to)-399.7(correlate)]TJ
0 -1.1174 TD
[(with)-472.1(neurodevelopmental)-470.7(outcome)-472.2(\(70\),)-468.5(educational)-477.9(level)]TJ
0 -1.1116 TD
[(\(71\),)-336.1(hearing)-338.4(impairment)-338.7(\(72\),)-336.1(and)-338.5(can)-333.9(be)-337.4(assessed)-339.8(by)-336.3(per-)]TJ
T*
[(forming)-441(a)-440(X-ray)-445.2(of)-439.9(the)-442.3(knee)-444.5(\(presence)-446.3(or)-439.9(absence)-444.1(of)-439.9(the)]TJ
0 -1.1174 TD
[(femoral)-535.5(and)-528.6(tibial)-532.4(epiphyses\).)-529.1(LT4)-529.8(treatment)-533.4(normalizes)]TJ
0 -1.1116 TD
[(bone)-201.4(maturation)-199.2(within)-203.7(the)-200.4(rst)-200(year)-202.5(of)-198(life)-201.6(\(70,73\).)-197.7(Although)]TJ
T*
[(disease)-287.4(severity)-287.6(can)-287.9(be)-285.6(derived)-286.6(from)-287.8(the)-286.8(rst)-286.4(diagnostic)-284.2(fT4)]TJ
0 -1.1174 TD
[(and)-188.8(TSH)-189.5(concentrations,)-190.7(a)-192.3(knee)-185.3(X-ray)-191.8(can)-189.9(be)-187.7(performed)-191.9(as)-187.5(an)]TJ
0 -1.1116 TD
[(additional)-434.3(parameter)-436.3(reecting)-433.9(the)-430.8(severity)-431.6(of)-434.1(intrauterine)]TJ
T*
(hypothyroidism.)Tj
/F11 1 Tf
8.9663 0 0 8.9663 62.022 260.4472 Tm
[(2.4.)-502.8(Associated)-332.7(malformations)-339.8(and)-331.9(syndromes)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 228.8692 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 227.5653 Tm
.0073 Tc
[(All)-431.7(n).4(eona)-6.5(tes)-431.3(w)-.4(ith)-431.5(CH)-426.6(s)-5.1(hould)-431.5(b).4(e)-426.9(e)-6.5(xamine)-6.5(d)-425.8(car)-5.3(eful)-5.4(ly)]TJ
0 -1.1116 TD
.0072 Tc
[(for)-281.8(d).3(y)-5.4(s).5(morp)-5.4(hic)-283(f).4(eat)-5.5(ures)-281.7(su)-5.4(gges)-5.2(tive)-283(f).4(o)-5.4(r)-276.1(s)-5.2(yndr)-5.4(omic)-283(CH,)]TJ
T*
.0083 Tc
[(and)-407.5(f)1.5(or)-407.5(congenital)-401.9(ma)-5.5(lformations)-401.5(\(particula)-5.5(rly)-407.5(cardi-)]TJ
0 -1.1174 TD
.0087 Tc
[(ac\))-332.2(\(1/)]TJ
/F4 1 Tf
2.7243 0 TD
.0067 Tc
(+++)Tj
/F3 1 Tf
1.6818 0 TD
.0068 Tc
(\).)Tj
/F12 1 Tf
8.9663 0 0 8.9663 72 166.1669 Tm
0 Tc
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 121.1527 166.1669 Tm
[(Permanent)-308.3(CH)-309.4(can)-305.1(be)-302.9(isolated)-305.1(or)-307.4(syndromic.)]TJ
-6.0074 -1.1116 TD
[(Careful)-339.4(clinical)-341.1(examination)-339.8(during)-335(the)-338.7(rst)-332.4(days)-339.4(of)-336.2(life)-334.1(is,)]TJ
0 -1.1174 TD
[(therefore,)-206.9(necessary)-204.2(to)-198.2(detect)-200.4(dysmorphic)-203.4(features)-202.2(suggestive)]TJ
0 -1.1116 TD
[(of)-215.3(a)-221.1(syndrome.)-216(Syndromic)-219.6(CH)-217.2(is)-215.2(mostly)-221(caused)-217.3(by)-215.3(mutations)]TJ
T*
[(in)-324.9(genes)-330.2(encoding)-328.1(transcription)-333.7(factors)-332.4(or)-324.7(involved)-327(in)-324.9(early)]TJ
0 -1.1174 TD
[(thyroid)-733.7(development.)-734.7(The)-731.4(BamforthLazarus)-739.8(syndrome)]TJ
0 -1.1116 TD
[(\(OMIM)-307.6(No.)-306(241850\))-307.2(is)-307.4(characterized)-316.4(by)-301.7(TD)-309.5(\(mainly)-309.8(athyr-)]TJ
T*
[(eosis)-288.6(or)-284.4(severe)-286.3(hypoplasia\),)-288.6(cleft)-290.3(palate,)-284.5(and)-286.7(spiky)-287.7(hair)-282.1(with)]TJ
0 -1.1174 TD
[(or)-284.4(without)-291.2(bilateral)-290.4(choanal)-287.8(atresia)-287.7(or)-290.2(bid)-280.8(epiglottis,)-292.5(and)-286.7(is)]TJ
0 -1.1116 TD
[(due)-298.2(to)-301.8(biallelic)-302(mutations)-300.5(in)-296.1(the)]TJ
/F5 1 Tf
13.2416 0 TD
(FOXE1)Tj
/F3 1 Tf
3.3579 0 TD
[(gene)-300.5(\(74\).)-301.5(Another)]TJ
-16.5995 -1.1116 TD
[(example)-450.3(of)-445.7(syndromic)-444.2(CH)-447.6(that)-449.3(can)-443.4(be)-446.9(recognized)-453.5(during)]TJ
25.504 67.9242 TD
[(neona)-7.8(tal)-402.1(period)-405.3(or)-405.3(early)-411.1(infancy)-401.8(is)-405.3(the)-407.8(brainlungthyroid)]TJ
0 -1.1174 TD
[(\(BLT\))-319.9(syndrome)-322(\(OMIM)-319.1(No.)-317.5(610978\))-312.9(due)-321.2(to)]TJ
/F5 1 Tf
18.9149 0 TD
(NKX2-1)Tj
/F3 1 Tf
3.5998 0 TD
(hap-)Tj
-22.5147 -1.1116 TD
[(loinsufcien)-9.8(cy,)-260.2(characterized)-270.3(by)-267.1(various)-262.2(types)-265.8(of)-261.4(CH,)-266.7(infant)]TJ
T*
[(respiratory)-308.2(distress)-309.1(syndrome,)-308.2(and)-304(benign)-301.6(hereditary)-308.4(chorea)]TJ
T*
[(\(75,76\).)-307.2(Other)-301.4(examples)-307.2(of)-301.7(syndromic)-306(CH)-303.6(are)-305.1(Alagille)-306.3(syn-)]TJ
0 -1.1174 TD
[(drome)-261.3(type)-253.4(1)-254.5(\(OMIM)-255.8(No.)-254.2(118450\))-255.4(with)-253.2(thyroid)]TJ
/F5 1 Tf
19.462 0 TD
[(in)-255.7(situ)]TJ
/F3 1 Tf
2.4824 0 TD
[(,)-256.9(liver)]TJ
-21.9445 -1.1116 TD
[(\(bile)-611.7(duct)-604.7(hypoplasia\),)-611.2(and)-603.5(cardiac)-611.5(malformations)-612.5(\(77\);)]TJ
T*
[(WilliamsBeure)-12.2(n)-352.4(\(OMIM)-359.5(No.)-357.9(194050\))-353.3(and)-355.8(DiGeorge)-364.3(syn-)]TJ
0 -1.1174 TD
[(dromes)-291(\(OMIM)-290.3(No.)-283(188400\))-289.9(with)-282(a)-290.2(high)-286.8(prevalence)-287.6(of)-290.1(thy-)]TJ
0 -1.1116 TD
[(roid)-442.2(hypoplasia)-439.6(\(5070%\))-436(and)-436.4(subcli)-7.8(nical)-434.3(hypothyroidism)]TJ
T*
[(\(2530%\))-332.4(\(78,79\);)-328(and)-321.2(Kabuk)-7.5(i)-323.8(\(80\))-326.9(and)-327(JohansonBlizzard)]TJ
0 -1.1174 TD
[(syndromes)-346(\(81\))-344.2(with)-339.6(a)-342.1(eutopic)-344.4(thyroid)-342(gland.)-344.3(Pendred)-343.9(syn-)]TJ
0 -1.1116 TD
[(drome)-359.2(due)-350(to)-353.7(mutations)-358.1(in)-353.7(the)]TJ
/F5 1 Tf
12.8787 0 TD
(SLC26A4)Tj
/F3 1 Tf
4.1873 0 TD
[(gene)-358.1(\(OMIM)-353.7(No.)]TJ
-17.066 -1.1116 TD
[(274600\),)-224.2(with)-218.6(or)-215.3(without)-222.1(goiter,)-218.8(should)-219.7(be)-222.2(considered)-221.8(in)-221.2(case)]TJ
T*
[(of)-319(congenital)-325.9(sensorineural)-322.9(hearing)-321.2(loss.)-318.6(Finally,)-317.8(the)-321.4(preva-)]TJ
0 -1.1174 TD
[(lence)-377.7(of)-365(congenital)-377.8(malformations,)-374(particularly)-374.3(cardiac)-369.6(de-)]TJ
0 -1.1116 TD
[(fects,)-212.8(including)-207.3(septal)-210.6(defects,)-210.4(and)-206.1(renal)-209.5(abnormalit)-9.2(ies)-206(\(82\))-205.9(is)]TJ
T*
[(higher)-238.3(in)-227(individuals)-238.2(with)-230.2(CH)-234.5(than)-230.3(in)-232.7(the)-235(general)-230.2(population,)]TJ
0 -1.1174 TD
[(with)-322.3(differences)-321.9(in)-319.1(prevalence)-328(between)-317.5(studies)-325.5(\(8389\);)-314.2(in-)]TJ
0 -1.1116 TD
[(deed,)-292.4(the)-286.8(reported)-287.7(frequency)-289.8(of)-290.1(cardiac)-288.9(defects)-287.6(in)-290.3(CH)-286.3(is)-290.1(be-)]TJ
T*
[(tween)-279.5(3%)-279.7(and)-275.2(11%,)-278.5(compared)-278.5(with)-282(0.5%)-272.7(to)-278.8(0.8%)-278.5(in)-273(all)-281.2(live)]TJ
0 -1.1174 TD
[(births.)-286.5(For)-279.6(Downs)-278.8(syndrome,)-285.1(see)-281.9(Section)-286.6(1.3.)]TJ
/F6 1 Tf
8.9663 0 0 8.9663 313.0582 470.0408 Tm
[(3.)-501.1(TREATMENT)-339(AND)-337.2(MONITORING)-335.4(OF)-331.2(CH)]TJ
/F3 1 Tf
9.843 0 0 9.843 322.9228 453.1463 Tm
[(3.1.)-498.6(Starting)-338.5(treatment)-337.5(for)-337.3(primary)-332.7(CH)]TJ
T*
[(3.2.)-498.6(Monitoring)-340.6(treatment)-337.5(in)-330.6(primary)-338.5(CH)]TJ
0 -1.1116 TD
[(3.3.)-498.6(Treatment)-338.6(and)-338.5(monitoring)-335.2(of)-330.5(central)-339.7(CH)]TJ
T*
[(3.4.)-498.6(Diagnostic)-331.2(re-evaluation)-330.3(of)-324.7(thyroid)-324.7(function)-327(beyond)]TJ
1.9986 -1.1174 TD
[(the)-338.7(rst)-332.5(6)-335.2(months)-336.1(of)-330.5(life)]TJ
-1.9986 -1.1116 TD
[(3.5.)-498.6(Treatment)-799.4(and)-793.5(monitoring)-790.2(of)-791.2(pregnant)-794.6(women)]TJ
1.9986 -1.1116 TD
[(with)-339.6(CH)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 313.0582 363.4015 Tm
[(3.1.)-502.8(Starting)-338.2(treatment)-336(for)-330.9(primary)-335.8(CH)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 331.8235 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 330.5196 Tm
[(LT4)-264.9(alone)-272.9(is)-261.3(recommended)-272.6(as)-268.1(the)-263.8(medication)-269.6(of)-267.1(choice)]TJ
0 -1.1116 TD
[(for)-337.3(the)-332.9(treatment)-337.5(of)-336.2(CH)-332.4(\(1/)]TJ
/F4 1 Tf
11.2026 0 TD
(++)Tj
/F3 1 Tf
1.1001 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 309.9401 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 308.6361 Tm
[(LT4)-247.6(treatment)-245.4(should)-242.7(be)-245.3(started)-246.2(as)-245.1(soon)-240.4(as)-245.1(possible,)-249.4(not)]TJ
0 -1.1116 TD
[(later)-555.2(than)-552.9(2)-548.3(weeks)-555.7(after)-549.3(birth)-552.9(or)-555.1(immediately)-554.2(after)]TJ
0 -1.1174 TD
[(conrmatory)-436(\(serum\))-441.8(thyroid)-434.2(function)-436.4(testing)-435.3(in)-434.3(neo-)]TJ
0 -1.1116 TD
[(nates)-508.9(in)-503.4(whom)-507.6(CH)-511(is)-503.2(detected)-509.1(by)-509(a)-503.3(second)-509.8(routine)]TJ
T*
[(screening)-335.8(test)-339.7(\(1/)]TJ
/F4 1 Tf
7.0211 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 255.118 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 253.8141 Tm
[(The)-236(LT4)-241.8(starting)-240.5(dose)-235.8(should)-236.9(be)-239.5(up)-232.6(to)-238.5(15)]TJ
/F14 1 Tf
16.588 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
[(g/kg)-240.7(per)-234.8(day,)]TJ
-17.1409 -1.1116 TD
[(taking)-290.3(into)-286.9(account)-287.8(the)-286.8(whole)-289.9(spectrum)-288.7(of)-290.2(CH,)-284(ranging)]TJ
T*
[(from)-333.9(mild)-334.2(to)-336.4(severe)-338.2(\(1/)]TJ
/F4 1 Tf
9.5842 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 222.2361 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 220.9322 Tm
[(Infants)-481(with)-483.6(severe)-482.2(CH,)-485.6(dened)-481.1(by)-480.3(a)-480.3(very)-483.6(low)-482.4(pre-)]TJ
0 -1.1116 TD
[(treatment)-423.9(serum)-416.6(fT4)-419.2(\()]TJ
/F4 1 Tf
9.2846 0 TD
(<)Tj
/F3 1 Tf
.5472 0 TD
[(5)-168.1(pmol/L\))-419.3(or)-416.9(total)-416(T4)-418.1(concen-)]TJ
-9.8318 -1.1116 TD
[(tration)-429.7(in)-422.8(combination)-425(with)-426(elevated)-428.4(TSH)-425.7(\(above)-429.4(the)]TJ
0 -1.1174 TD
[(normal)-239.5(range)-238.2(based)-243.8(on)-232.6(time)-243.2(since)-238.2(birth)-236.1(and)-240.6(GA\),)-238.8(should)]TJ
0 -1.1116 TD
[(be)-372(treated)-380(with)-368.4(the)-373.2(highest)-377.6(starting)-373(dose)-374(\(1015)]TJ
/F14 1 Tf
20.0438 0 TD
(l)Tj
/F3 1 Tf
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(g/kg)Tj
-20.5967 -1.1116 TD
[(per)-332.7(day\))-339.6(\(1/)]TJ
/F4 1 Tf
4.8439 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 156.4724 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 155.2252 Tm
[(Infants)-337.1(with)-328.1(mild)-334.2(CH)-332.4(\(fT4)]TJ
/F4 1 Tf
11.0644 0 TD
(>)Tj
/F3 1 Tf
.72 0 TD
[(10)-169.2(pmol/L)-331.8(in)-330.6(combination)]TJ
-11.7844 -1.1174 TD
[(with)-379.9(elevated)-388.1(TSH\))-380.7(should)-380.9(be)-383.5(treated)-380(with)-385.7(the)-379(lowest)]TJ
0 -1.1116 TD
[(initial)-389.7(dose)-391.3(\()]TJ
/F10 1 Tf
5.2989 0 TD
(*)Tj
/F3 1 Tf
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(10)Tj
/F14 1 Tf
1.1692 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
[(g/kg)-390.4(per)-384.6(day\);)-392.7(in)-388.2(infants)-389(with)-391.4(pre-)]TJ
-8.0175 -1.1116 TD
[(treatment)-544.9(fT4)-534.4(concentrations)-544.4(within)-537.8(the)-540.2(age-specic)]TJ
0 -1.1174 TD
[(reference)-338.2(interval,)-337.5(an)-337.4(even)-335(lower)-335.9(starting)-332.7(dose)-333.7(may)-334(be)]TJ
0 -1.1116 TD
[(considered)-337(\(from)-334.9(5)-335.2(t)0(o)-330.6(1)0(0)]TJ
/F14 1 Tf
10.4078 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
[(g/kg\))-333.9(\(1/)]TJ
/F4 1 Tf
3.5653 0 TD
(++)Tj
/F3 1 Tf
1.1001 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 90.7653 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 89.4614 Tm
[(LT4)-270.6(should)-271.5(be)-268.3(administered)-277.3(orally,)-270.6(once)-271.7(a)-267.2(day)-275.2(\(1/)]TJ
/F4 1 Tf
20.1878 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 79.7669 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 78.463 Tm
[(The)-524(evidence)-526.2(favoring)-522.7(brand)-525(versus)-525.7(generic)-523.9(LT4)-524.1(is)]TJ
0 -1.1116 TD
[(mixed,)-403.1(but)-395.1(based)-405.1(on)-399.6(personal)-402.7(experience/expert)-407.3(opin-)]TJ
T*
[(ion,)-335.2(we)-332.5(recommend)-332.6(brand)-334.9(rather)-337.3(than)-328.2(generic)-339.6(\(2/)]TJ
/F4 1 Tf
20.1878 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F6 1 Tf
8.9663 0 0 8.9663 62.022 749.6502 Tm
(396)Tj
40.9535 0 TD
[(VAN)-332.3(TROTSENBURG)-337.1(ET)-338.7(AL.)]TJ
ET
endstream
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BT
/F12 1 Tf
8.9663 0 0 8.9663 69.7323 725.7825 Tm
0 0 0 rg
0 Tc
0 Tw
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 118.9417 725.7825 Tm
.0111 Tc
[(There)-348.3(a)-2.7(r)4.3(e)-354(no)-347.1(rand)4.2(omized)-347.1(cli)4.1(n)-1.5(i)4.1(c)-2.7(al)-353(t)4.1(r)-1.5(ials)-346.9(that)]TJ
-6.0131 -1.1116 TD
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[(s)-5.2(u)-5.4(pp)-5.4(or)-5.4(t)-477.8(a)-478.9(sp)-5.4(e)-6.6(c)-.8(i)-5.5().5(c)-478.9(t)-5.5(re)-6.6(at)-5.5(me)-6.6(nt)-477.8(a)-6.6(p).3(p)-5.4(r)-5.4(o).3(a)-6.6(c)-.8(h)-477.7(i)-5.5(n)-477.7(C)-.7(H)-478.6(w)-6.3(it)-5.5(h)-477.7(h).3(i)-5.5(g).3(h)-5.4(-)]TJ
0 -1.1174 TD
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[(quali)5.1(ty)-294.3(evi)5.1(d)-.5(ence.)-296.6(S)-.4(i)5.1(n)-.5(ce)-301.2(th)5.2(e)-301.2()5.4(rst)-294.4(e)-1.7(nt)5.1(hu)5.2(si)5.1(ast)5.1(i)-.6(c)-295.4(r)-.5(ep)5.2(or)5.3(ts)-299.8(o)5.2(n)-300(th)5.2(e)]TJ
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[(success)5.2(ful)-323.4(treat)4.9(m)-1.9(ent)-323.4(o)-.7(f)-329()56.9(sp)5(o)-.7(r)5.1(a)-1.9(d)5(i)-.8(c)-330.2(c)3.9(reti)4.9(nis)5.2(m)-1.9()51.2()-323.2(wi)4.9(th)-329(t)4.9(h)-.7(y)5(r)-.7(o)5(i)-.8(d)]TJ
T*
.0125 Tc
[(ex)5.6(tract)5.5(s)-495.3(deriv)5.6(e)-1.3(d)-495.4(f)5.7(rom)-490.9(an)5.6(imal)-495.6(th)5.6(yr)5.7(oi)5.5(d)-495.4(g)-.1(land)5.6(s,)-492(all)-495.6(f)5.7(ur)5.7(th)5.6(er)]TJ
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[(s)-5.2(p)-5.4(ec)-6.6(ti)-5.5(ve)-432.8(or)-431.6(p)-5.4(r).4(o)-5.4(s)-5.2(pe)-6.6(ct)-5.5(iv)-5.4(e)-427(o)-5.4(bs)-5.2(e)-6.6(r).4(v)-5.4(a)-.8(t)-5.5(i)-5.5(o).3(n)-5.4(a)-.8(l)-431.8(s).5(t)-5.5(u)-5.4(di)-5.5(es)-431.4(on)-5.4(l)-5.5(y).3(.)-428.2(H)-6.3(ow)-6.3(-)]TJ
T*
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[(ev)6.1(er,)-243.9(t).3(od)6.1(ay)-247.3(a)-248.4(l).3(a)5(r).4(g)6.1(e)-254.2(s)6.3(e)-.8(r)6.2(i).3(es)-247.1(o)6.1(f)-253(s)6.3(u).4(ch)-247.3(c)5(o).4(h)6.1(ort)-247.4(st)6(ud)6.1(ie)5(s)-252.9(i)6(s)-252.8(a)5(va)5(il)6(abl)6(e)]TJ
0 -1.1174 TD
.0103 Tc
[(that)-261.6(w)-3.2(e)2.3(re)-262.7(unde)-3.5(rtake)-3.5(n)-255.7(to)-261.5(corre)-3.5(l)]TJ
12.3488 0 TD
[(a)-3.4(t)3.4(e)-262.6()-2(na)-3.4(l)-261.5(o)3.5(utcome)-262.6(to)-255.6(different)]TJ
-12.3488 -1.1116 TD
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[(tre)5(a)-.8(t)6(m)-.8(e)5(n).4(t)-230.1(s).6(t)6(r).4(a)5(t).3(e)5(g).4(i)6(e)-.8(s.)-226.6(Ini)6(ti)6(al)6(ly)-230(so)6.1(ma)5(ti)6(c)-236.9(d)6.1(ev)6.1(el)6(op)6.1(me)5(nt)-230.1(in)-230(t)6(e)-.8(rm)4.9(s)]TJ
T*
.0122 Tc
[(of)-346(gr)5.4(owth)-346(and)-346(p)5.3(ub)5.3(ert)5.2(y)-346(was)-345.8(s)-.2(t)5.2(udi)5.2(ed)5.3(,)-348.3(b)5.3(ut)-346.1(l)5.2(a)-1.6(ter)-346(o)-.4(n)-346(c)4.2(og)5.3(ni)5.2(tiv)5.3(e)]TJ
T*
.0119 Tc
[(out)4.9(co)5(methe)-312.9(mo)5(st)-311.9(pr)5.1(ecio)5(us,)-308.3(b)-.7(u)5(t)-311.9(als)5.2(o)-311.7(vu)5(ln)5(erabl)4.9(e)-312.9(develo)5(p-)]TJ
0 -1.1174 TD
.0132 Tc
[(me)5.2(nt)6.2(al)-414.2(ou)6.3(tc)5.2(om)5.1(e)5.3(be)5.2(ca)5.2(me)-415.3(t)6.2(h).6(e)-415.3(f)]TJ
13.328 0 TD
.0116 Tc
[(ocus)-415.5(of)-415.7(s)4.9(u)-1(ch)-415.7(stu)4.7(d)-1(i)4.6(e)-2.2(s)4.9(.)-418(Th)4.7(e)]TJ
-13.328 -1.1116 TD
.0131 Tc
[(hig)6.2(h).5(e)5.1(s).7(t)-322.2(l)6.1(ev)6.2(el)-316.4(of)-322(e)5.1(v).5(id)6.2(en)6.2(ce)-317.5(wa)5.1(s)-321.9(g).5(a)5.1(i).4(n)6.2(e)-.7(d)-322.1(b)6.2(y)-322.1(t).4(h)6.2(o).5(s)6.4(e)-323.2(st)6.1(ud)6.2(ies)-316.1(t).4(ha)5.1(t)]TJ
T*
.0119 Tc
[(ass)5.2(e)-1.9(s)5.2(s)-.5(ed)-259.9(t)4.9(h)-.7(e)-261.1(c)-1.9(o)5(g)-.7(n)5(iti)4.9(ve)-261.1(ou)5(tcome)-261.1(\()-.7(in)5(tell)4.9(igence)-261.1(quo)5(ti)4.9(en)5(t)-265.8([)5.1(IQ]\))]TJ
0 -1.1174 TD
.0126 Tc
[(in)-501.1(i)5.6(n)0(d)5.7(i)-.1(vi)5.6(du)5.7(al)5.6(s)-500.9(w)-.9(i)5.6(t)-.1(h)-501.1(C)4.7(H)-502(a)4.6(nd)-501.1(u)5.7(n)0(affect)5.6(ed)-501.1(s)5.9(i)-.1(b)5.7(lin)5.7(g)-501.1(c)4.6(ont)5.6(ro)5.7(ls)5.9(.)]TJ
0 -1.1116 TD
.0119 Tc
[(To)5(gether,)-314.1(t)4.9(he)-312.9(avail)4.9(a)-1.9(b)5(l)-.8(e)-312.9(d)-.7(ata)-312.9(a)-1.9(ll)4.9(ow)-312.6(fo)5(r)-317.5(r)-.7(eli)4.9(a)-1.9(b)5(l)-.8(e)-312.9(c)-1.9(o)5(n)-.7(clus)5.2(io)5(ns)]TJ
T*
.0072 Tc
[(a)-6.6(n).3(d)-270.4(r)-5.4(ec)-6.6(om)-6.6(me)-6.6(nd)-5.4(at)-5.5(io)-5.4(ns)-5.2(.)-266.9(O)-6.3(ne)-271.5(s)-5.2(u).3(c)-6.6(h)-264.6(c)-6.6(o).3(n)-5.4(c)-.8(l)-5.5(u)-5.4(si)-5.5(on)-270.4(is)-270.2(t)-5.5(h).3(a)-6.6(t)-264.7(o)-5.4(n)-5.4(e)-265.8(c)-6.6(a)-.8(n)]TJ
0 -1.1174 TD
.0117 Tc
[(ex)4.8(pect)-289(a)-290.1(f)4.9(av)4.8(orabl)4.7(e)-290.1(o)-.9(u)4.8(t)-1(come)-290.1(in)-288.9(mos)5(t)-289(ch)4.8(il)4.7(dren)-288.9(w)-1.8(i)4.7(t)-1(h)-288.9(C)3.8(H)-289.8(w)4(ho)]TJ
0 -1.1116 TD
.0072 Tc
[(w)-6.3(e)-.8(r)-5.4(e)-237(gi)-5.5(v)-5.4(e)-.8(n)-235.8(t)-5.5(he)-237()46.5().4(r)-5.4(i)-5.5(gh)-5.4(t)46.5()-235.8(t)-5.5(re)-6.6(at)-5.5(me)-6.6(nt)-5.5(.)-238.1(I).4(n)-235.8(t)-5.5(hi)-5.5(s)-235.6(r).4(e)-6.6(s)-5.2(pe)-6.6(ct)-5.5(,)-232.4(n)-5.4(um)-6.6(er)-5.4(ou)-5.4(s)]TJ
T*
[(o)-5.5(u)-5.5(t).1(c)-6.7(o).2(m)-6.7(e)-455.9(st)-5.6(ud)-5.5(ie)-6.7(s)-454.6(p)-5.5(oi)-5.6(nt)-454.9(t)-5.6(o)-454.8(a)-455.9(s)-5.3(tr)-5.5(on)-5.5(g)-454.8(i)-5.6(mpa)-6.7(c)-6.7(t)-454.9(of)-454.7(t)-5.6(w)-.6(o)-454.8(\()-5.5(ma)-6.7(in)-5.5(\))]TJ
T*
.0119 Tc
[(facto)5(r)-.7(s)-271.2(t)-.8(h)5(a)-1.9(t)-271.6(i)-.8(n)5()-.6(u)5(e)-1.9(nce)-272.6(c)-1.9(o)5(gni)4.9(ti)4.9(ve)-272.6(ou)5(tcome:)-271.6(th)5(e)-278.3(a)3.9(ge)-272.6(at)-277.3(s)5.2(t)-.8(ar)5.1(t)-271.5(o)-.7(f)]TJ
0 -1.1174 TD
.0131 Tc
[(LT)5.1(4)-276(t).4(re)5.1(at)6.1(me)5.1(nt)-276.1(a)5.1(n).5(d)-276(t).4(h)6.2(e)-277.1(LT)5.1(4)-276(s).7(ta)5.1(rt)6.1(ing)-276(d)6.2(ose)5.1(.)]TJ
/F5 1 Tf
1.0137 -2.2981 TD
0 Tc
[(Age)-414.6(at)-417(start)-420.1(of)-411.3(treatment)-422.2(and)-412.2(starting)-417.7(dose.)]TJ
/F3 1 Tf
18.8227 0 TD
.019 Tc
[(Bea)5.2(r).7(ing)-356.5(i).5(n)]TJ
-19.8364 -1.1116 TD
.0187 Tc
[(mind)-184(t)6(h).3(at)-184.1(th)6.1(ese)-185.1(f).4(ac)4.9(tors)-183.8(w)5.2(e)-.8(re)-185.1(not)-184.1(s)6.3(t).2(udie)4.9(d)-184(syste)4.9(m)-.9(at)6(ical)6(ly,)-186.3(o)6.1(ne)]TJ
0 -1.1174 TD
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[(can)-374.3(o)5.9(n).1(ly)-374.3(d)5.9(e)-1(duce)-375.4(c)-1(o)5.9(n).1(clu)5.9(s).3(ions)-368.3(and)-374.3(r)5.9(ecommen)5.9(dati)5.8(ons)-374.1(fr)5.9(om)]TJ
0 -1.1116 TD
[(obser)5.9(vati)5.8(onal)-282.2(s).3(tud)5.9(i)0(es.)-284.4(T)4.7(herefore,)-284.4(t)5.8(he)-283.3(reco)5.9(mmendat)5.8(i)0(ons)-281.9(on)]TJ
T*
.0181 Tc
[(the)-324(o)-.3(p)5.5(timal)-322.9(age)-324(a)4.3(t)-322.9(s)-.1(tart)-322.9(o)5.5(f)-322.8(LT4)-322.8(t)5.4(r)-.2(eatment)-322.9(and)-322.8(t)-.4(he)-324(o)5.5(p)-.3(timal)]TJ
T*
.0183 Tc
[(start)5.6(i)-.2(ng)-213.2(dose)-214.3(a)-1.2(re)-214.3(ded)5.7(u)-.1(ced)-213.2(from)-214.4(r)0(easonably)-213.2(powered)-213.2(stud)5.7(ies)]TJ
0 -1.1174 TD
.0189 Tc
[(that)-460.4(e)5.1(v).5(entu)6.3(ally)-460.3(d)6.3(e)-.6(mon)6.3(s).7(trat)6.2(ed)-460.2(no)-460.2(dif)6.3(f).6(eren)6.3(ce)-461.4(in)-460.3(co)6.3(gniti)6.2(ve)]TJ
0 -1.1116 TD
.0186 Tc
[(outcome)-571.2(bet)5.9(w)-.6(een)-570(ind)6(i).1(vidu)6(als)-569.8(w)-.6(ith)-570(CH)-570.9(and)-570(unaffect)5.9(ed)]TJ
T*
.0183 Tc
[(sibli)5.6(ngs.)-417.1(S).1(o)-420.5(f)0(ar)-420.5(onl)5.6(y)-420.5(t)-.2(wo)-414.8(such)-414.8(studi)5.6(es)-420.3(are)-415.9(a)-1.2(vailabl)5.6(e.)-417.1(In-)]TJ
0 -1.1174 TD
[(itially,)-203.9(t)-.1(wo)-201.6(outcome)-202.7(studi)5.7(es)-207.1(in)-201.6(young)-201.6(adul)5.7(t)-207.5(C)-1(H)-202.4(p)0(ati)5.7(e)-1.1(nts)-207.1(a)4.6(nd)]TJ
0 -1.1116 TD
[(sibli)5.6(n)-.1(g)-259.3(c)4.5(ontro)5.7(ls)-259.1(sh)5.7(owed)-253.5(an)-253.5(IQ)-260.1(gap)-259.3(o)-.1(f)-253.5(e)-1.2(ig)5.7(ht)-259.4(po)5.7(ints.)-255.8(I)5.7(n)-259.3(t)-.2(hese)]TJ
T*
.018 Tc
[(obser)5.4(vati)5.3(onal)-305.8(s)-.2(tudi)5.3(es,)-308(t)-.5(reatment)-311.5(was)-311.2(s)-.2(t)5.3(a)-1.5(rted)-311.4(at)-305.8(an)-311.4(average)]TJ
0 -1.1174 TD
.0187 Tc
[(age)-323.4(o).3(f)-322.2(2).3(4)-328(d)6.1(ays)-322(a)-.8(nd)-322.2(with)-322.2(ave)4.9(r).4(age)-323.4(L)-.9(T)4.9(4)-328(do)6.1(se)]TJ
/F4 1 Tf
18.4656 0 TD
0 Tc
(<)Tj
/F3 1 Tf
.5644 0 TD
.0184 Tc
(10)Tj
/F14 1 Tf
1.2038 0 TD
0 Tc
(l)Tj
/F3 1 Tf
.5702 0 TD
.0187 Tc
[(g)6.1(/).2(kg)-322.2(per)]TJ
-20.8041 -1.1116 TD
[(day.)-255.5(The)-254.4().4(rst)-253.3(s).4(tud)6(y)-259(t)5.9(h).2(at)-253.3(repo)6(rted)-253.2(no)-253.2(gap)-253.2(c)-.9(o)6(m)-1(par)6(i).1(ng)-253.2(44)-253.2(CH)]TJ
T*
.0182 Tc
[(and)-391.8(5)-.2(3)-397.6(u)-.2(n)5.6(a)-1.3(ffected)-391.8(sibl)5.5(ing)-397.6(c)4.4(ontr)5.6(o)-.2(ls)-397.4(with)-397.6(a)-393(m)-1.4(edian)-391.8(a)-1.3(ge)-393(at)]TJ
T*
.019 Tc
[(time)-472.8(o).6(f)-477.4(t).5(es)6.6(ting)-477.4(o)6.4(f)-477.4(9)-477.4(y).6(ear)6.4(s)-477.2(w)-.2(as)-477.2(fr)6.4(om)-478.7(Ne)5.2(w)-478.3(Z)-.6(ea)5.2(land)-477.4(a)5.2(n).6(d)]TJ
0 -1.1174 TD
.0184 Tc
[(publ)5.7(ished)-443.5(i)5.7(n)-443.5(2013)-443.5(\()5.8(90\).)-440(P).2(ati)5.7(e)-1.1(nts)-443.3(w)4.9(ere)-444.6(t)-.1(reated)-437.7(with)-443.5(LT4)]TJ
0 -1.1116 TD
.0167 Tc
[(from)-250.6(a)-250.5(me)-2.8(a)-2.8(n)-249.3(age)-250.5(o)-1.7(f)-249.3(9)-249.3(d)-1.7(a)-2.8(y)4.1(s)-249.1(w)-2.5(ith)-249.3(a)-250.5(s)-1.5(ta)-2.8(rting)-249.3(dose)-250.5(b)-1.7(etw)-2.5(e)-2.8(en)-249.3(10)]TJ
T*
.019 Tc
[(and)-442.9(1).6(5)]TJ
/F14 1 Tf
3.1448 0 TD
0 Tc
(l)Tj
/F3 1 Tf
.5702 0 TD
.0183 Tc
[(g/k)5.7(g)-443.6(dependin)5.7(g)-443.6(on)-443.6(CH)-444.4(severi)5.6(ty.)-440.1(N)-.9(eon)5.7(a)-1.2(tes)-443.4(w)4.8(ith)]TJ
-3.715 -1.1174 TD
[(athy)5.6(reosi)5.5(s)-374.4(were)-370(treated)-368.8(w)4.7(ith)-368.8(15)]TJ
/F14 1 Tf
13.639 0 TD
0 Tc
(l)Tj
/F3 1 Tf
.5702 0 TD
.0186 Tc
[(g/kg)-368.4(p)6(e)-.9(r)-368.4(d).2(ay)6(.)-370.7(T)-1(SH)-369.3(n)6(o).2(r-)]TJ
-14.2092 -1.1116 TD
.0189 Tc
[(mali)6.2(zed)-247.1(wi)6.2(thin)-247.1(a)-248.3(m)5.1(edi)6.2(a)-.6(n)-247.1(o).5(f)-247.1(1).5(4)-247.1(d).5(a)5.1(y).5(s)-246.9(a)-.6(ft)6.2(er)-247.1(diag)6.3(nosis)6.5(.)-249.5(P).7(ow)5.4(er)]TJ
T*
.0179 Tc
[(calculat)5.2(i)-.6(on)-323(predict)5.2(e)-1.6(d)-323(t)-.6(hat)-323.1(t)-.6(he)-324.2(number)-323(o)-.5(f)-323(p)5.3(atients)-322.8(a)-1.6(nd)-323(s)5.5(i)-.6(b-)]TJ
0 -1.1174 TD
[(lings)-351.5(wo)5.4(uld)-351.7(b)-.4(e)-352.9(s)-.2(uf)5.5(c)-1.5(ien)5.4(t)-357.6(t)5.3(o)-357.5(d)5.4(e)-1.5(tect)-357.6(a)-352.9(d)5.4(iffer)5.4(e)-1.5(nce)-352.9(o)-.4(f)-351.7(5)-.4(.2)-351.7(IQ)]TJ
0 -1.1116 TD
[(poin)5.2(t)-.7(.)-498.2(T)-1.8(here)-502.8(was)-501.5(n)5.2(o)-501.7(s)-.4(i)5.1(gnicant)-496(d)-.6(iff)5.2(e)-1.7(rence)-502.8(b)5.2(etween)-501.7(t)5.1(h)-.6(e)]TJ
T*
[(tested)-282.8(p)5.2(a)-1.7(tients)-282.6(a)4(nd)-277(sibli)5.1(ngs.)]TJ
1.0137 -1.1174 TD
0 Tc
[(The)-299.4(second)-302.5(study)-299.2(reporting)-299.3(no)-301.7(gap)-298.2(comparing)-301.6(76)-295.9(CH)-297.8(pa-)]TJ
-1.0137 -1.1116 TD
[(tients)-290.2(and)-286.7(40)-290.2(sibling)-284.4(controls)-292.2(was)-287.4(from)-287.8(Berlin)-285.5(and)-286.7(was)-287.4(pub-)]TJ
T*
[(lished)-353.4(in)-353.7(2018)-350(\(91\).)-347.6(The)-351.2(treatment)-354.8(approach)-352.1(resembled)-354.4(the)]TJ
T*
[(New)-311.5(Zealand)-312(approach)-306(with)-310.8(a)-301.8(median)-309.8(age)-310.9(at)-308.8(diagnosis)-304.7(of)-307.4(8)]TJ
0 -1.1174 TD
[(days,)-354.4(a)-347.8(mean)-353.5(LT4)-351.3(starting)-355.7(dose)-351(of)-347.7(13.5)]TJ
/F14 1 Tf
16.4843 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
[(g/kg)-350.1(per)-350(day,)-347.7(and)]TJ
-17.0372 -1.1116 TD
[(TSH)-189.5(normalizing)-188.8(within)-192.2(a)-186.6(median)-188.8(time)-185.6(of)-186.5(15)-186.5(days.)-187.4(In)-186.5(contrast)]TJ
T*
[(to)-267.3(the)-263.8(New)-271.2(Zealand)-266(study,)-268.1(the)-263.8(mean)-267.1(ages)-271.5(of)-261.4(the)-269.5(patients)-264.8(and)]TJ
0 -1.1174 TD
[(controls)-205.8(were)-203.4(18.1)-196.8(and)-200.3(19.8)-202.6(years,)-201.1(respectively.)-205.8(There)-204.8(was)-201(no)]TJ
0 -1.1116 TD
[(signicant)-445.4(difference)-447.7(in)-440.1(overall)-448(IQ)-440.8(\(102.5)-440.9(vs.)-443.2(102.5\),)-438.6(nor)]TJ
T*
[(were)-284(there)-284.4(differences)-281.6(in)-284.5(other)-277.5(\(cognitive\))-285.5(tests)-283(of)-278.6(attention,)]TJ
0 -1.1174 TD
[(memory,)-324.7(ne)-315.3(motor)-317.9(skills,)-321.1(quality-of-life)-324.6(scores,)-317.2(and)-321.2(in)-313.4(an-)]TJ
0 -1.1116 TD
[(thropometric)-351.2(measurements.)-346(In)-342(addition,)-342.1(there)-347.7(was)-345(no)-342(neg-)]TJ
T*
[(ative)-566.8(effect)-563.1(of)-560.9(episodes)-563.8(of)-566.6(overtreatment)-561.9(in)-566.8(terms)-560.7(of)-560.9(a)]TJ
25.5097 67.9242 TD
[(suppressed)-565.7(TSH.)-561.6(Even)-565.5(in)-561(the)-563.3(children)-564.3(with)-564.2(the)-563.3(highest)]TJ
0 -1.1174 TD
[(number)-343(of)-342(episodes)-344.9(of)-342(TSH)-345(suppression,)-344.5(IQ)-342.9(and)-344.3(other)-346.6(out-)]TJ
0 -1.1116 TD
[(come)-278.7(parameters)-287.5(did)-279.9(not)-279.9(differ.)]TJ
1.0137 -1.1116 TD
.0241 Tc
[(Bas)5.9(e)-1.2(d)-576(o)0(n)-576(t)-.2(h)5.7(e)-577.2(evi)5.6(d)0(ence)-577.2(fr)5.8(om)-577.2(fo)5.7(ur)-576(st)5.6(udi)5.6(es)-575.8(rep)5.7(o)0(r)5.8(tin)5.7(g)]TJ
-1.0137 -1.1116 TD
.0244 Tc
[(si)5.9(bl)5.9(ing)6(-).3(co)6(ntr)6.1(o).3(ll)5.9(ed)-201.3(cog)6(n).3(it)5.9(ive)-202.5(o).3(u)6(t).1(co)6(me)-202.5(data,)-203.7(o).3(n)6(e)-208.2(can)-201.3(d).3(ed)6(uce)]TJ
0 -1.1174 TD
.0237 Tc
[(and)-236.6(c)4.2(onclud)5.3(e)-237.7(th)5.3(at)-236.7(a)-237.7(e)4.2(ven)-230.8(a)-237.7(ch)5.3(ild)-236.6(w)4.5(ith)-230.8(sev)5.3(e)-1.6(re)-237.7(CH)-237.5(can)-236.6(r)-.4(each)]TJ
0 -1.1116 TD
.0234 Tc
[(a)-180.4(n)-.7(o)5(r)-.7(mal)-179.4(I)-.7(Q)-180.2(t)-.9(hat)-185.2(d)5(oes)-179.1(n)-.7(o)5(t)-185.2(d)5(i)-.9(ff)5.1(er)-179.3(fro)5(m)-180.5(unaffected)-185(s)5.2(i)-.9(bl)4.9(in)5(gs,)-181.6(i)4.9(f)]TJ
T*
.0236 Tc
[(LT4)-259.7(t)5.1(reatment)-259.9(i)5.1(s)-259.5(started)-259.7(b)-.5(ef)5.3(ore)-255.1(the)-260.9(a)4.1(ge)-260.9(o)5.2(f)-259.7(10)-259.7(days)-259.5(an)5.2(d)-259.7(t)-.7(he)]TJ
0 -1.1174 TD
.0244 Tc
[(st)5.9(ar)6.1(tin)6(g)-218.6(d)6(ose)-214(i)5.9(s)-218.4(a)4.9(t)-213(l).1(ea)4.9(st)-213(10)]TJ
/F14 1 Tf
10.834 0 TD
0 Tc
(l)Tj
/F3 1 Tf
.576 0 TD
.0242 Tc
[(g/)5.7(kg,)-209.6(wit)5.7(h)-213(15)]TJ
/F14 1 Tf
5.656 0 TD
0 Tc
(l)Tj
/F3 1 Tf
.5702 0 TD
.0242 Tc
[(g/k)5.8(g)-213(in)-213(the)-214.2(m)4.6(os)6(t)]TJ
-17.6362 -1.1116 TD
.0232 Tc
[(severe)-330.4(fo)4.8(rms.)-331.6(Mor)4.9(e)-330.4(preci)4.7(se)-330.4(va)]TJ
12.9709 0 TD
.0239 Tc
[(lu)5.5(es)-328.3(fo)5.5(r)-328.5(t)-.4(he)-323.9(opt)5.4(imal)-328.7(age)-329.7(a)4.4(t)]TJ
-12.9709 -1.1116 TD
.0245 Tc
[(st)6(ar)6.2(t)-201.4(o)6.1(f)-201.2(L)4.9(T4)-195.5(tr)6.2(ea)5(tme)5(n).4(t)-195.6(o).4(r)-195.4(t).2(h)6.1(e)-196.6(sta)5(r).4(ti)6(ng)-195.5(dos)6.3(e)-196.6(l).2(ea)5(din)6.1(g)-195.5(to)-195.5(suc)5(h)-201.2(a)]TJ
0 -1.1174 TD
.0234 Tc
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T*
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T*
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(l)Tj
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T*
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T*
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0 -1.1174 TD
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T*
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T*
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12.8096 0 TD
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T*
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T*
.0122 Tc
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0 -1.1116 TD
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T*
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T*
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0 -1.1116 TD
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T*
.012 Tc
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0 -1.1174 TD
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T*
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T*
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/F11 1 Tf
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[(We)-357(recommend)-361.4(evaluation)-354.7(of)-353.5(fT4)-355.8(and)-355.8(TSH)-356.5(according)]TJ
0 -1.1174 TD
[(to)-336.4(age-specic)-340.2(reference)-338.2(intervals)-340.7(\(1/)]TJ
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/F6 1 Tf
8.9663 0 0 8.9663 59.7543 749.7069 Tm
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(interval.)Tj
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()Tj
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[(If)-480.2(TSH)-483.3(is)-480.2(in)-480.4(the)-482.6(age-specic)-484.2(reference)-487.9(interval,)-481.5(fT4)]TJ
T*
[(concentrations)-417.7(above)-416.8(the)-419.3(upper)-415.6(limit)-416.2(of)-416.9(the)-413.5(reference)]TJ
0 -1.1174 TD
[(interval)-408.9(can)-408.8(be)-412.3(accepted)-412.2(and)-407.6(recommend)-413.3(maintaining)]TJ
0 -1.1116 TD
[(the)-332.9(same)-336.1(LT4)-334(dose)-333.7(\(1/)]TJ
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()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 648.4534 Tm
[(Any)-234.6(reduction)-242.9(of)-238.3(the)-240.7(LT4)-236.1(dose)-241.5(should)-236.9(not)-239.6(be)-239.5(based)-238(on)-238.3(a)]TJ
0 -1.1174 TD
[(single)-532(higher)-526.2(than)-535.6(normal)-527.5(fT4)-534.4(concentration,)-529.6(unless)]TJ
0 -1.1116 TD
[(TSH)-408.4(is)-411.1(suppre)-7.5(ssed)-408.4(\(i.e.,)-412.3(below)-416.6(the)-407.8(lower)-416.6(limit)-410.4(of)-411.1(the)]TJ
T*
[(reference)-390(interval\))-386.9(or)-382.3(there)-388.1(are)-385.7(signs)-385.4(of)-382.3(overtreatment)]TJ
0 -1.1174 TD
[(\(e.g.,)-331.5(jitteriness)-337.2(or)-336.2(tachycardia\))-341.8(\(1/)]TJ
/F4 1 Tf
14.1862 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 594.9353 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 593.6313 Tm
-.0167 Tc
[(The)-439.4()-.4(r)5.3(s)-.3(t)-438.4(c)-1.7(li)5.1(nical)-438.4(a)-1.7(n)5.2(d)-438.3(bio)5.2(c)-1.7(hemical)-438.4(f)-.5(o)5.2(llo)5.2(w-up)-438.3(eval)5.1(uat)5.1(i)-.6(on)]TJ
0 -1.1116 TD
-.0172 Tc
[(sh)4.7(oul)4.6(d)-456(t)-1.1(ake)-451.4(p)-1(lace)-457.2(1)-450.3(t)-1.1(o)-456(2)-450.3(weeks)-450.1(a)-2.2(fter)-456(th)4.7(e)-457.2(s)-.8(t)4.6(a)-2.2(rt)-450.4(of)-456(LT4)]TJ
T*
-.0156 Tc
[(t)6.2(r).6(eat)6.2(me)5.2(nt)-339.4(\()6.4(1)-339.2(we)5.2(ek)-339.2(a)5.2(t)-339.4(th)6.3(e)-340.4(l).5(a)5.2(t).5(es)6.5(t)-339.4(i).5(n)-333.5(case)-334.6(o).6(f)-333.4(a)-340.4(st)6.2(arti)6.2(ng)-339.2(d)6.3(o).6(se)]TJ
0 -1.1174 TD
-.0174 Tc
[(close)-244.3(t)-1.3(o)-243.1(1)-1.2(5)]TJ
/F14 1 Tf
4.3428 0 TD
0 Tc
(l)Tj
/F3 1 Tf
.5357 0 TD
-.0163 Tc
[(g)5.6(/)-.2(kg)-242(per)-242(d)-.1(ay)-242(or)-247.8(an)-247.8(ev)5.6(en)-242(high)5.6(er)-247.8(d)5.6(o)-.1(se\))-247.8(\(1/)]TJ
/F4 1 Tf
15.4303 0 TD
0 Tc
(+)Tj
/F3 1 Tf
.5357 0 TD
-.0162 Tc
[(00)5.7(\).)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 72 551.1117 Tm
0 Tc
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 549.8077 Tm
[(Subsequent)-894.4(\(clinical)-895.1(and)-897.2(biochemical\))-894.9(evaluation)]TJ
0 -1.1116 TD
[(should)-432.8(take)-438.8(place)-435.3(every)-439.8(2)-433.1(weeks)-440.5(until)-432.1(complete)-440(nor-)]TJ
0 -1.1174 TD
[(malization)-511.6(of)-509(serum)-508.8(TSH)-506.3(is)-509(achieved;)-510.2(therafter,)-512.3(the)]TJ
0 -1.1116 TD
[(evaluation)-268.3(frequency)-272.5(can)-270.6(be)-274.1(lowered)-270.2(to)-267.3(once)-271.7(every)-272.7(1)-266(t)0(o)]TJ
T*
[(3)-329.4(months)-336.1(until)-334.2(the)-338.7(age)-333.9(of)-330.5(12)-336.3(months)-336.1(\(1/)]TJ
/F4 1 Tf
16.4785 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 496.2896 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 494.9857 Tm
[(Between)-353.1(the)-355.9(ages)-352.1(of)-353.5(12)-353.5(months)-353.4(and)-350(3)-352.4(years,)-356.6(the)-350.2(eval-)]TJ
0 -1.1116 TD
[(uation)-612.8(frequency)-612.3(can)-610.4(be)-613.9(lowered)-610(to)-612.9(every)-612.6(2)-605.9(t)0(o)-612.9(4)]TJ
T*
[(months;)-464(thereafter,)-468.5(evaluations)-465.1(should)-467.3(be)-464.1(carried)-466.3(out)]TJ
0 -1.1174 TD
[(every)-295.8(3)-289.1(t)0(o)-296.1(6)-289.1(months)-295.8(until)-293.9(growth)-295.6(is)-290.1(completed)-297.1(\(1/)]TJ
/F4 1 Tf
20.2396 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 452.466 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 451.1621 Tm
[(If)-388(abnormal)-386.9(fT4)-390.4(or)-382.3(TSH)-391.1(values)-389(are)-385.7(found,)-389(or)-388.1(if)-382.4(com-)]TJ
0 -1.1116 TD
[(pliance)-357(is)-347.7(questioned,)-356.7(the)-355.9(evaluation)-354.7(frequency)-358.9(should)]TJ
T*
[(be)-331.7(increased)-337(\(2/)]TJ
/F4 1 Tf
6.52 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 419.5841 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 418.2802 Tm
-.0216 Tc
[(Aft)-5.5(e)-.8(r)-270.3(a)-277.3(cha)-6.6(nge)-271.5(o)-5.4(f)-270.3(LT)-6.6(4)-270.4(dos)-5.2(e)-271.5(o).3(r)-276.1(f).4(or)-5.4(mul)-5.5(a)-.8(ti)-5.5(on)-5.4(,)-266.9(a)-6.6(n)-270.4(e)-.8(xt)-5.5(ra)-271.5(e)-6.6(v).3(al)-5.5(-)]TJ
0 -1.1116 TD
[(uat)-5.5(i).2(on)-276.1(sh)-5.4(oul)-5.5(d)-270.4(b).3(e)-271.5(c)-6.6(arr)-5.4(i).2(e)-6.6(d)-270.4(out)-276.3(aft)-5.5(e)-.8(r)-270.3(4)-276.1(to)-270.4(6)-270.4(w)-6.3(eek)-5.4(s)-270.2(\().4(2)-5.4(/)]TJ
/F4 1 Tf
19.3181 0 TD
0 Tc
(+)Tj
/F3 1 Tf
.5357 0 TD
-.0219 Tc
[(00\))-5.7(.)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 72 397.644 Tm
0 Tc
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 396.3968 Tm
[(Adequate)-393.4(treatment)-395.1(throughout)-385.6(childhood)-391.5(is)-393.8(essential,)]TJ
0 -1.1174 TD
[(and)-482.5(long-term)-484.8(under-)-480(or)-486(overtreatment,)-484.7(that)-483.9(is,)-483.6(TSH)]TJ
0 -1.1116 TD
[(concentrations)-429.2(above)-428.3(or)-422.6(below)-428.1(the)-425(reference)-436.1(interval,)]TJ
T*
[(should)-334.8(be)-331.7(avoided)-338.5(\(1/)]TJ
/F4 1 Tf
8.9045 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 353.8204 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 352.5164 Tm
[(In)-365(contrast)-368.3(to)-365.2(adults,)-368.4(in)-365.2(neonates,)-372.8(infants)-366(and)-367.3(children)]TJ
0 -1.1116 TD
[(LT4)-351.3(can)-351.2(be)-354.7(administered)-357.9(together)-351.2(with)-356.9(food)-350(\(but)-350.1(with)]TJ
T*
[(avoidance)-492.8(of)-491.7(soy)-486.9(protein)-492.9(and)-488.3(vegetable)-492.9(ber\);)-491.5(more)]TJ
T*
[(important,)-235(LT4)-236.1(should)-236.9(be)-233.8(administered)-237(at)-239.6(the)-235(same)-232.4(time)]TJ
0 -1.1174 TD
[(every)-243.9(day,)-244(also)-247.4(in)-244.2(relation)-247.6(to)-244.2(food)-246.3(intake.)-243(This)-247.4(approach)]TJ
0 -1.1116 TD
[(can)-374.2(improve)-378.8(compliance,)-377.7(and)-378.8(ensures)-378.2(as)-371.8(consistent)-382(as)]TJ
T*
[(possible)-378.5(LT4)-374.3(absorption)-380.8(and)-378.8(as)-377.5(good)-373(as)-377.5(possible)-378.5(LT4)]TJ
0 -1.1174 TD
[(dose)-333.7(titration)-334.2(\(2/)]TJ
/F4 1 Tf
6.8022 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 266.1732 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 264.8692 Tm
[(In)-365(case)-370.6(of)-365(an)-366.2(unexpected)-367.1(need)-369.6(for)-366.1(LT4)-368.6(dose)-368.2(increase,)]TJ
0 -1.1116 TD
[(reduced)-402.8(absorption)-409.6(or)-399.6(increased)-406.1(metabolization)-407.9(of)-405.3(T4)]TJ
0 -1.1174 TD
[(by)-342(other)-346.6(disease)-345(\(e.g.,)-348.8(gastrointestinal\),)-348.5(food,)-341.9(or)-347.7(medi-)]TJ
0 -1.1116 TD
[(cation)-510.3(should)-507.6(be)-510.2(considered)-509.7(\(2/)]TJ
/F4 1 Tf
13.5641 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
[(00\);)-505.6(noncompliance)]TJ
-14.117 -1.1116 TD
[(may)-264.9(be)-262.5(the)-263.8(most)-264.8(frequent)-264.6(cause,)-265.7(especially)-269.3(in)-261.5(teenagers)]TJ
0 -1.1174 TD
[(and)-332.8(adolescents.)]TJ
/F12 1 Tf
8.9663 0 0 8.9663 72 183.1181 Tm
(Evidence)Tj
/F5 1 Tf
9.843 0 0 9.843 72 166.1669 Tm
[(Shortly)-406.4(after)-409.9(the)-407.8(start)-402.8(of)-411.3(LT4)-406.2(treatment.)]TJ
/F3 1 Tf
17.1754 0 TD
[(Repeated)-360.2(mea-)]TJ
-18.1892 -1.1116 TD
[(surement)-432.7(of)-428.4(serum)-433.9(fT4)-430.7(and)-430.7(TSH,)-429.1(and)-430.7(clinical)-433.3(assessment)]TJ
0 -1.1174 TD
[(\(especially)-235.8(for)-233.6(signs)-229.9(of)-232.6(overtreatment)-233.6(when)-231.1(using)-230.1(the)-235(highest)]TJ
0 -1.1116 TD
[(starting)-252(dose\))-248.4(are)-253.3(the)-246.5(backbone)-254.2(of)-249.8(monitoring)-248.8(LT4)-247.6(treatment)]TJ
T*
[(in)-209.7(patients)-212.9(with)-207.1(primary)-211.8(CH)-205.7(\(9597\).)-212.7(TSH)-206.8(normalizes)-217.4(slower)]TJ
0 -1.1174 TD
[(than)-397.4(fT4.)-393.8(Therefore,)-398.1(the)-396.3(rst)-395.8(treatment)-400.9(goal)-397.4(is)-393.8(as)-394.8(rapid)-398.4(as)]TJ
0 -1.1116 TD
[(possible)-199.9(normalization)-203.8(of)-203.8(fT4.)-198(Since)-203.6(fT4)-200.3(reects)-201(the)-200.4(unbound)]TJ
T*
[(biologically)-338.7(active)-338.7(form)-339.6(of)-336.2(T4,)-335.1(measurement)-341.7(of)-336.2(fT4)-332.8(is)-336.2(pre-)]TJ
0 -1.1174 TD
[(ferred)-412(to)-405.5(total)-410.2(T4)-412.3(\(98\).)-405.2(The)-414.6(second)-406.2(treatment)-412.4(goal)-414.6(is)-405.3(nor-)]TJ
0 -1.1116 TD
[(malization)-621(of)-612.7(TSH)-615.7(within)-618.4(4)-611.6(weeks.)-616.7(Consequently,)-619.1(fT4)]TJ
T*
[(\(or)-262.4(total)-266.2(T4\))-263.7(should)-260(guide)-266(dosing)-265.7(until)-259.3(TSH)-264.4(reaches)-265.6(the)-263.8(age-)]TJ
25.504 67.9242 TD
[(specic)-264.4(reference)-263.3(interval)-259.2(\(99\).)-261.2(Rapid)-255.5(normalization)-261.4(of)-261.4(TSH)]TJ
0 -1.1174 TD
[(and)-332.8(keeping)-327(fT4)-332.8(in)-324.9(the)-332.9(upper)-329.2(half)-328.2(of)-330.5(the)-327.1(age-specic)-334.5(refer-)]TJ
0 -1.1116 TD
[(ence)-370.8(interval)-374.4(have)-363.8(been)-369.6(shown)-369(to)-370.9(optimize)-369.9(the)-367.5(neurodeve-)]TJ
T*
[(lopmental)-284.6(outcome)-282.1(\(90,1001)-6.5(02\).)]TJ
/F5 1 Tf
1.0137 -2.2348 TD
[(Follow-up)-294.6(after)-289(the)-286.8(rst)-292.1(weeks)-292.1(of)-284.6(LT4)-291(treatment.)]TJ
/F3 1 Tf
20.038 0 TD
[(There)-233.6(is)]TJ
-21.0517 -1.1116 TD
[(no)-468.7(evi)12.7(den)12.8(ce)-465.3(for)-464(a)-468.8(one)-459.5(opt)13.8(ima)11.5(l)-473.5(fol)19.6(low)13(-up)-464(sch)13(eme)16.2(.)-475.7(R)0(e)12.9(cen)11.7(t)]TJ
0 -1.1174 TD
[(stu)14(die)12.7(s)-594.2(foc)12.8(usi)14(ng)-583.9(on)-583.9(opt)13.8(imi)12.5(za)12.8(tio)13.7(n)-594.3(o)0(f)-583.9(bio)13.9(che)17.4(mic)11.5(al)-585.2(thy)13.8(roi)13.9(d)]TJ
0 -1.1116 TD
[(fun)14(cti)12.6(on)-203.8(tes)12.9(tin)13.7(g)-208.4(sug)14.2(ge)13.9(st)-203.7(the)-200.4(imp)12.6(ort)13.9(anc)17.4(e)-209.6(o)0(f)-203.8(fre)12.9(que)12.8(nt)-203.9(la)13.8(bor)14(ato)12.7(ry)]TJ
T*
[(mon)12.7(ito)13.7(rin)13.9(g)-312.1(and)-298.2(dos)14.2(e)-313.3(adj)12.7(ust)14(men)11.6(t)-306.5(dur)14(ing)-302.9(the)-304.1(rs)14.4(t)-306.5(yea)11.7(r)-312.1(o)0(f)-307.4(lif)13.8(e.)]TJ
0 -1.1174 TD
[(Fin)14(din)13.8(gs)-209.4(in)-203.9(the)12.7(se)-210.5(stu)14(die)12.7(s)-208.3(wer)12(e)-209.6(tha)12.7(t)-214.3(\(i\))-199.2(pat)12.7(ien)12.7(ts)-209.5(wit)12.8(h)-208.4(sev)13(ere)-201.4(CH)]TJ
0 -1.1116 TD
[(\(at)12.7(hyr)14(eos)13(is)-238.3(and)-229.1(dys)14.2(gen)12.8(esi)12.9(s)-242.8(vs.)-230.1(dys)14.2(hor)14(mon)12.7(oge)12.8(ne)13.9(sis,)-231.1(wit)12.8(h)-237.2(hig)13.9(h)]TJ
T*
[(TSH)-247.1(va)13.9(lue)12.7(s)-254.3(a)0(t)-245.4(dia)12.7(gno)14(sis)14.2(\))-248.7(nee)11.7(d)-248.8(mor)12.8(e)-249.9(dos)14.2(e)-249.9(adj)12.7(ust)14(men)11.6(ts)-244(dur)14(ing)]TJ
0 -1.1174 TD
[(the)-200.4(rs)14.4(t)-202.8(yea)11.7(r)-202.7(o)0(f)-203.8(lif)13.8(e)-203.8(\(10)14(3,1)11.6(04)15.1(\);)-203.9(\(ii)13.8(\))-202.6(the)-200.4(hi)14.9(ghe)12.8(st)-203.7(dos)14.2(es)-199(wit)12.8(hin)-193.5(the)]TJ
0 -1.1116 TD
[(rec)11.7(omm)11.5(end)12.8(ed)-239.5(ran)12.8(ge)-245.3(of)-244.1(10)14(15)]TJ
/F14 1 Tf
12.0666 0 TD
(l)Tj
/F3 1 Tf
.5472 0 TD
[(g/k)13.9(g)-243(per)-240.6(day)-240.6(res)13(ult)13.7(ed)-245.3(in)-238.5(mor)12.8(e)]TJ
-12.6138 -1.1116 TD
[(dos)14.2(e)-365.1(a)0(d)13.9(jus)14(tme)11.5(nts)-348.8(bec)11.7(aus)13(e)-359.4(o)0(f)-353.5(hyp)14(ert)12.7(hyr)14(oxi)13.8(nem)17.3(ia)-354.8(\(10)14(51)14(07\))14(;)]TJ
T*
[(and)-229.1(\(ii)13.8(i\))-226.9(mon)12.7(thl)13.7(y)-231.5(thy)13.9(roi)13.9(d)-231.5(fun)14(cti)12.6(on)-226.8(tes)12.9(tin)13.7(g)-237.2(l)0(e)13.8(d)-237.2(to)-227(fre)12.9(que)12.8(nt)-227(dos)14.2(e)]TJ
0 -1.1174 TD
[(adj)12.7(ust)14(men)11.6(ts)-198(dur)14(ing)-187.7(the)-194.7(rs)14.4(t)-202.8(yea)11.7(r)-196.9(o)0(f)-198(lif)13.8(e)-203.8(\(75)14(%)-198(a)0(t)-199.3(06)-193.4(mo)13.9(nth)13.8(s)-202.5(o)0(f)]TJ
0 -1.1116 TD
[(age)11.7(,)-251.1(and)-240.6(36%)-234.8(at)-245.4(71)14(2)-248.8(mon)12.7(ths)-239.4(of)-244.1(age)11.7(\))-248.7(\(97)14(\).)-240.6(How)12.2(eve)11.6(r,)-240.6(in)-244.2(non)14(e)]TJ
T*
[(of)-583.9(the)12.7(se)-584.9(stu)14(die)12.7(s)-588.4(neu)12.8(rod)14(eve)11.7(lop)13.9(me)12.7(nta)12.7(l)-588.7(out)13.8(com)11.6(e)-589.8(d)0(a)13.9(t)0(a)-585.2(wer)12(e)]TJ
0 -1.1174 TD
[(ava)11.7(ila)12.6(ble)12.7(,)-205(the)-194.7(mos)12.9(t)-202.8(imp)12.6(ort)13.9(ant)-194.7(lon)13.9(g-t)13.9(erm)-195.7(tre)12.7(atm)17.2(ent)-194.7(goa)12.8(l)-208.6(i)0(n)-198.2(CH.)]TJ
0 -1.1116 TD
[(Wit)11.4(h)-237.2(t)0(h)15(i)0(s)-232.5(i)0(n)-227(min)12.6(d,)-229.2(the)-223.5(fol)13.9(low)13(-up)-222.1(sch)13(eme)10.4(s)-237.1(t)0(h)15(a)0(t)-233.9(wer)12(e)-232.7(cho)12.8(sen)-223.1(in)]TJ
T*
[(the)-281.1(stu)14(die)12.7(s)-283.1(tha)12.7(t)-289.2(rep)12.8(ort)13.9(ed)-279.8(nor)14(mal)-276.5(IQ)-285.3(out)13.8(com)17.3(es)-285.4(can)-276.3(be)-285.6(use)13(d)-283.3(a)0(s)]TJ
0 -1.1174 TD
[(rec)11.7(omm)11.5(end)12.8(ati)12.6(on)15.1(.)-262.6(I)0(n)-255.6(the)-252.3(New)-253.9(Zea)10.5(lan)12.7(d)-260.3(and)-252.1(the)-252.3(Ber)11.8(lin)-251.2(stu)14(die)12.7(s,)]TJ
0 -1.1116 TD
[(tre)12.7(atm)11.5(ent)-384.7(eff)12.9(ect)11.5(ive)12.7(nes)13(s)-392.6(i)0(n)-388.2(ter)12.7(ms)-389.1(of)-388.1(nor)14(ma)12.7(liz)12.6(ati)12.6(on)-388.1(of)-388.1(ser)13.1(um)]TJ
T*
[(par)12.8(ame)10.4(ter)12.7(s)-225.5(was)-218.3(tes)12.9(ted)-217.7(wee)16.5(kly)-216.5(aft)12.7(er)-222.2(the)-217.7(sta)12.9(rt)-221.2(of)-221(tre)12.7(atm)17.2(ent)-217.7(unt)13.8(il)]TJ
0 -1.1174 TD
[(the)12.7(y)-317.9(nor)14(mal)11.5(iz)13.8(ed)-314.4(\(90)14(,91)17.4(\).)-315.5(The)17.4(rea)11.7(fte)12.7(r,)-309.8(in)-313.4(New)-311.5(Ze)12.7(ala)11.5(nd,)-305.1(blo)13.8(od)]TJ
0 -1.1116 TD
[(tes)12.9(ts)-307.4(we)13(re)-308.6(don)19.7(e)-313.3(m)0(o)13.8(nth)13.8(ly)-301.8(dur)14(ing)-297.2(the)-298.3(rs)14.4(t)-312.3(y)0(e)13.9(a)0(r)-308.6(a)0(n)13.9(d)-312.1(bim)18.4(ont)13.8(hly)]TJ
T*
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T*
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T*
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T*
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[(T)-4.7(S)2.4(H)-309.6(c)-4.6(oncentrations.)-311.1(T)1.1(his)-314.3(may)]TJ
13.1149 0 TD
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[(b)-5.3(e)-311.7(du)-5.3(e)-311.7(t).4(o)-316.3(l).4(ac)-6.4(k)-310.5(o).5(f)-316.3(t).4(h)-5.3(yro)-5.3(id)-5.3(al)]TJ
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[(pr)4.1(od)4.1(uct)4(i)-1.8(o)4.1(n)-255.1(o)4.1(f)-255.1(T3)-255.1(t)4(h)4.1(at)-249.5(needs)-249.2(t)-1.8(o)-249.3(b)-1.7(e)-250.5(c)-2.8(o)4.1(m)2.9(pens)4.3(ated)-255.1(b)4.1(y)-255.1(a)-250.5(h)4.1(ig)4.1(her)]TJ
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[(fT4)-279.2(c)-3.9(oncentration.)]TJ
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[(centrations)-384.4(are)-374.2(scarce.)-377.3(In)-376.5(two)-378.7(studies,)-375(long-term)-375.4(follow-up)]TJ
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[(suggested)-323(a)-319(decreased)-326.5(IQ)-319.8(at)-320.3(the)-315.6(age)-322.4(of)-319(11)-319(years,)-322.1(and)-321.2(an)-314.4(in-)]TJ
T*
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[(\(108,109\).)-413(Earlier)-408.8(studies)-411.9(suggested)-409.4(adverse)-414.2(effects)-408.5(on)-405.4(at-)]TJ
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[(tention)-216.6(span)-212.7(\(110\).)-210.5(However,)-216.8(Aleksander)]TJ
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16.5822 0 TD
[(et)-216.6(al.)]TJ
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T*
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T*
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0 -1.1116 TD
[(pituitarythyroid)-435.3(feedback)-439.7(axis)-431.7(after)-434.1(intrauterine)-431.9(hypothy-)]TJ
T*
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0 -1.1174 TD
[(cially)-792.6(in)-791.4(patients)-788.9(younger)-792.2(than)-789(12)-791.3(months)-785.3(\(24,111\).)]TJ
0 -1.1116 TD
[(Persist)-8.6(ence)-353.5(of)-359.3(such)-356.7(mild)-357.2(hypothalamuspituitary)-363.6(resistance)]TJ
T*
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0 -1.1174 TD
[(tients)-284.4(with)-282(acquired)-283.1(hypothyroidism)-281.8(\(112\).)]TJ
1.0137 -1.1116 TD
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/F6 1 Tf
8.9663 0 0 8.9663 62.022 749.6502 Tm
0 Tc
(398)Tj
40.9535 0 TD
[(VAN)-332.3(TROTSENBURG)-337.1(ET)-338.7(AL.)]TJ
ET
endstream
endobj
165 0 obj
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T*
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T*
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T*
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T*
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0 -1.1174 TD
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0 -1.1116 TD
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T*
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T*
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[(p)-5.6(e)-1(rio)-5.6(d)-391.5(of)-397.2(tr)-5.5(ansi)-5.7(tion)-397.2(t).1(o)-397.2(a)-1(dul)-5.7(t)-391.6(c)-1(a)-6.7(r).2(e)-392.6(a)-1(r)-5.5(e)-392.6(cr)-5.5(iti)-5.7(cal)-391.6(p)-5.6(e)-1(ri)-5.7(ods.)-393.8(I)-5.5(n-)]TJ
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[(d)-5.4(i).3(vid)-5.4(u).4(ali)-5.5(zed)-281.8(f)-5.3(o).4(llo)-5.4(w-up)-287.6(sche)-6.5(mes)-281.6(s)-5.2(houl)-5.5(d)-281.8(b).4(e)-283(d)-5.4(rawn)-287.6(up)-281.8(to)-281.8(a)-6.5(s).6(-)]TJ
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[(s)-5.2(ure)-490.3(norma)-6.5(l)-483.6(gro)-5.4(wth)-483.4(a)-6.5(nd)-483.4(pu)-5.4(bert)-5.5(y)-483.4(i).3(n)-489.2(t).3(he)-484.6(ad)-5.4(oles)-5.2(cent)-5.5(,)-485.8(and)]TJ
T*
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[(f)-5.6(e)-1.1(rti)-5.8(lit)-5.8(y)-276.4(i)-5.8(n)-282.1(t)0(he)-283.3(you)-5.7(ng)-282.1(adu)-5.7(l)0(t)-282.3(\(114)-5.7(\).)]TJ
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[(Adverse)-323(effects)-316.7(of)-313.4(LT4.)]TJ
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9.6993 0 TD
[(Adverse)-264.1(effects)-270.3(of)-261.4(long-term)-265.9(LT4)]TJ
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[(pseudotumor)-204.5(cerebri)-201.3(or)-198(craniosynostosis)-203.8(have)-196.8(been)-196.8(described)]TJ
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[(\(115,116\).)-384.2(However,)-378(relative)-387(macrocrania)-382.1(at)-383.6(the)-379(age)-380(of)-376.5(18)]TJ
T*
[(months,)-402.9(but)-400.9(without)-406.4(any)-401.9(case)-399.4(of)-405.3(craniosynostosis,)-403.1(was)-402.6(re-)]TJ
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[(ported)-347.7(in)-347.9(a)-347.8(cohort)-347.7(of)-342(45)-347.8(CH)-349.7(patients)-345.4(with)-345.4(documented)-349.9(fT4)]TJ
0 -1.1116 TD
[(concentrations)-193(above)-186.4(the)-188.9(reference)-194.2(interval)-190(during)-185.3(their)-185.4(rst)-188.5(6)]TJ
T*
[(to)-261.5(9)-260.3(months)-261.2(of)-261.4(life)-259.2(\(117\).)-262.3(In)-255.6(one)-263.7(cohort)-261.3(of)-255.6(young)-264.7(adults)-261.3(with)]TJ
T*
[(CH,)-428(cardiovascular)-435.9(abnormalities)-434(were)-428(reported)-431.7(\(impaired)]TJ
0 -1.1174 TD
[(diastolic)-433(dysfunction)-433.8(and)-430.7(exercise)-428.1(capacity,)-437.6(and)-424.9(increased)]TJ
0 -1.1116 TD
[(intima)-447.1(media)-441.2(thickness,)-447.5(IMT\);)-445.4(however,)-440.5(the)-448.1(clinical)-444.8(rele-)]TJ
T*
[(vance)-412.2(of)-405.3(these)-410.9(ndings)-410.7(remains)-408.6(unknown.)-409.4(Moreover,)-412.8(in)-405.5(a)]TJ
0 -1.1174 TD
[(large)-393.8(nationwide)-394.7(study,)-394.8(standardized)-398(mortality)-392.9(ratio)-392.8(in)-388.2(pa-)]TJ
0 -1.1116 TD
[(tients)-353.5(with)-345.4(CH)-349.7(was)-345(not)-349(increased)-354.3(for)-343.1(diseases)-351.7(of)-347.7(the)-350.2(circu-)]TJ
T*
[(latory)-284.5(system)-285.2(\(87\).)]TJ
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1.0137 -1.8604 TD
[(Cardiac)-534(insufcienc)-10(y.)]TJ
/F3 1 Tf
9.6187 0 TD
[(LT4)-483.8(has)-482.3(clear)-481.4(positive)-482.5(ino-)-476.8(and)]TJ
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[(chronotropic)-280.7(effects)-281.8(on)-278.7(the)-275.3(heart.)-282.1(In)-272.9(newly)-278.4(diagnosed)-282.9(CH)-274.8(in)]TJ
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[(newborns)-258.3(with)-259(congenital)-256.8(heart)-255.6(disease)-258.6(and)-252.1(impending)-260.2(heart)]TJ
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[(failure,)-555.1(we)-557.2(therefore)-554.8(recommend)-557.3(to)-549.5(apply)-554(a)-555.2(lower)-554.8(LT4)]TJ
T*
[(starting)-614.9(doseapproximately)-620.2(50%)-614.9(of)-612.7(the)-609.4(recommended)]TJ
T*
[(doseand)-495.9(to)-491.9(increase)-491.4(it)-492(guided)-491.7(by)-491.8(serum)-491.5(fT4)-494(and)-494(TSH)]TJ
0 -1.1174 TD
[(measurement,)-287.5(and)-280.9(the)-281.1(infants)-286.4(clinical)-283.5(condition.)]TJ
/F5 1 Tf
1.0137 -1.8546 TD
[(Impaired)-293(bioavailability)-296.2(by)-291.3(diseases,)-290.6(drugs,)-290.8(or)-290(food.)]TJ
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21.5298 0 TD
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[(LT)5.7(4)]TJ
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T*
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T*
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T*
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T*
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T*
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[(barbi)5.5(tal,)-192.5(ph)5.6(en)5.6(yt)5.5(oi)5.5(n,)-192.5(an)5.6(d)-195.9(c)4.5(ar)5.7(ba)]TJ
12.0723 0 TD
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[(mazepin)4.9(e)-2(\))-190.9(a)-2(n)4.9(d)-196.6(ri)4.8(famp)4.9(icin)-190.9(wi)4.8(ll)]TJ
-12.0723 -1.1174 TD
.0092 Tc
[(increa)-4.6(se)-459.6(its)-452.5(m)1.1(e)-4.6(t)-3.5(abol)]TJ
8.5704 0 TD
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T*
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1.0137 -1.1174 TD
0 Tc
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T*
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25.5097 67.9242 TD
[(matically,)-208.7(LT4)-207.3(should)-208.1(be)-204.9(administered)-213.9(at)-205.1(a)-209.6(xed)-207(time)-208.6(with)-207.1(an)]TJ
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T*
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T*
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[(CH)-280.6(\(127,128\).)]TJ
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[(3.3.)-496.4(Treatment)-339.5(and)-331.9(monitoring)-335.5(of)-336.6(central)-335.1(CH)]TJ
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()Tj
/F3 1 Tf
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[(In)-255.6(severe)-257.5(forms)-254.1(of)-255.6(central)-259.1(CH)-251.8(\(fT4)]TJ
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[(5)-162.4(pmol/L\),)-255.7(we)-257.7(also)]TJ
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T*
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(l)Tj
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(g/kg)Tj
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[(the)-338.7(normal)-331.6(range)-336.1(\(1/)]TJ
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(l)Tj
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[(g/kg)-321.3(per)-321.2(day\))-322.3(to)]TJ
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[(reduce)-338.4(the)-332.9(risk)-338.4(of)-330.5(overtreatment)-343.1(\(1/)]TJ
/F4 1 Tf
14.6066 0 TD
(++)Tj
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(0\).)Tj
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()Tj
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[(In)-457.2(newborns)-459.9(with)-460.6(central)-460.7(CH,)-456.8(we)-459.3(recommend)-459.3(moni-)]TJ
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[(toring)-323.6(treatment)-331.8(by)-319(measuring)-330.2(fT4)-321.3(and)-327(TSH)-322(according)]TJ
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[(should)-473.1(be)-469.9(kept)-466.5(above)-474.4(the)-465.4(mean)-8(/median)-466.5(value)-474.5(of)-468.7(the)]TJ
T*
[(age-specic)-472.7(reference)-470.7(interval;)-473.5(if)-463.1(TSH)-466(is)-468.7(low)-465.1(before)]TJ
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[(treatment,)-744.1(subsequent)-738.8(TSH)-736.7(determinations)-740.4(can)-737.1(be)]TJ
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[(omitted)-338.8(\(1/)]TJ
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(00\).)Tj
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()Tj
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[(When)-307.3(under-)-301.5(or)-301.7(overtreatment)-308.5(is)-301.6(suspec)-8.5(ted)-298.3(in)-301.8(a)-307.5(patient)]TJ
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[(with)-368.4(central)-368.5(CH,)-370.4(then)-362.8(TSH)-368.1(or)-365(fT3)-367.3(or)-365(T3)-366.3(can)-368.5(be)-366.2(mea-)]TJ
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[(sured)-340.5(\(1/)]TJ
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3.6171 0 TD
(+)Tj
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(00\).)Tj
/F13 1 Tf
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()Tj
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[(interval,)-613.9(then)-604.7(undertreatment)-614.9(should)-605.6(be)-608.1(considered,)]TJ
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[(particularl)-10.3(y)-329.4(i)0(f)-336.4(TSH)]TJ
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(>)Tj
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[(1.0)-166.9(mU/L)-336.1(\(1/)]TJ
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5.2586 0 TD
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(00\).)Tj
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()Tj
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[(tered)-370.8(just)-367.3(before)-366(blood)-368.5(withdrawal\),)-371.3(particularly)-368.5(if)-370.9(as-)]TJ
T*
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[(\(f)-88.5(\)T3)-332.8(concentration)-336.1(\(1/)]TJ
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(+)Tj
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(00\).)Tj
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(Evidence.)Tj
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[(consists)-441.6(of)-434.1(daily)-438.9(administration)-445.6(of)-434.1(LT4)-437.7(\(orally;)-442.3(tablets)-442.2(or)]TJ
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[(liquid)-450.5(dosage)-452.2(form\).)-447.8(The)-449.2(biggest)-452.4(differences)-454.3(between)-455.7(the)]TJ
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[(treatment)-360.6(of)-353.5(primary)-361.5(and)-355.8(central)-362.8(CH)-355.4(are)-356.9(in)-359.4(the)-355.9(monitoring)]TJ
T*
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[(most)-449.1(important)-450.4(parameterand)-454.5(in)-445.8(the)-448.1(LT4)-449.2(starting)-453.6(dose.)]TJ
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[(Important)-358.1(to)-353.7(realize)-363.9(is)-353.5(that)-357.2(in)-359.4(central)-357(CH,)-358.9(a)-359.4(low)-355.6(TSH)-356.5(con-)]TJ
T*
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[(The)-512.5(\(biochemical\))-515.9(LT4)-512.6(treatment)-516.1(aim)-512.7(is)-509(bringing)-515.9(and)]TJ
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[(keeping)-332.7(the)-332.9(fT4)-332.8(concentration)-341.9(in)-330.6(the)-332.9(upper)-334.9(half)-334(of)-330.5(the)-332.9(age-)]TJ
T*
[(specic)-206.8(fT4)-206.1(reference)-211.5(interval.)-205(Although)-205.8(randomized)-211.7(clinical)]TJ
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(<)Tj
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[(5)-162.4(pmol/L\),)-520.7(but)-516.1(most)-518.2(cases)-521.2(can)-524(be)-516(classied)-520(as)-521.5(mild)-518.5(to)]TJ
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[(moderate)-226.7(\(fT4)-230.2(at)-222.4(diagnosis)-229.8(515)-165.7(pmol/L\))-229.2(\(20,131\).)-227.6(Although)]TJ
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[(studies)-285.2(investigating)-287.8(the)-286.8(optimal)-281.2(starting)-286.6(dose)-287.6(in)-284.6(central)-287.9(CH)]TJ
T*
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[(starting)-614.9(dose)-615.9(of)-612.7(1015)]TJ
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10.1832 0 TD
(l)Tj
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[(g/kg)-615.1(in)-618.6(mild-to-moderate)-617.3(cases)]TJ
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[(quickly)-550.5(results)-555.9(in)-549.5(supraphysiol)-8.5(ogical)-550.6(fT4)-551.6(concentrations.)]TJ
T*
[(So,)-241.6(with)-247.4(exception)-249.8(of)-249.8(severe)-246(cases,)-253.9(a)-244.2(lower)-249.5(starting)-246.3(dose)-247.3(that)]TJ
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[(is)-278.6(510)]TJ
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3.1102 0 TD
(l)Tj
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[(g/kg)-281(is)-284.4(advisable.)]TJ
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8.9663 0 0 8.9663 59.7543 749.7069 Tm
[(GUIDELINES)-340.4(FOR)-334(CONGENITAL)-339.9(HYPOTHYROIDISM)-28059.1(399)]TJ
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[(beyond)-334.9(the)-334.7(rst)-335.4(6)-333.2(months)-333.5(of)-336.6(life)]TJ
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1.1128 -1.8336 TD
(Summary)Tj
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7.9702 0 0 7.9702 72 683.2628 Tm
()Tj
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[(When)-485.9(no)-486(denitive)-484.8(diagnosis)-489(of)-486(permanent)-487(CH)-487.9(was)]TJ
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[(made)-509.1(in)-509.2(the)-511.4(rst)-505.2(weeks)-515.4(or)-509(months)-508.9(of)-509(life,)-510.3(then)-506.8(re-)]TJ
0 -1.1116 TD
[(evaluation)-285.6(of)-290.2(the)-286.8(HPT)-287.4(axis)-287.7(after)-284.4(the)-286.8(age)-287.9(of)-284.4(2)-289.1(t)0(o)-284.6(3)-283.3(years)]TJ
T*
[(is)-307.4(indicated,)-305.2(particularly)-310.9(in)-307.6(children)-305.1(with)-310.8(a)-307.5(GIS,)-306.9(and)-304(in)]TJ
0 -1.1174 TD
[(those)-334.9(with)-333.8(presumed)-334.7(isolated)-339.6(central)-334(CH)-338.2(\(1/)]TJ
/F4 1 Tf
18.1546 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 628.4408 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 627.1368 Tm
[(Fo)21(r)-266(a)-261.4(pr)15.1(ec)18.5(is)20.9(e)-267.2(d)0(i)20.7(a)0(g)19.7(n)0(o)20.8(s)0(i)15.1(s)0(,)-252(L)0(T)18.4(4)-266(tr)20.7(ea)18.5(tm)19.5(en)19.7(t)-266.2(s)0(h)21(o)0(u)15.1(l)0(d)-255.8(b)0(e)-251(p)0(h)15.1(a)0(s)19.9(e)0(d)]TJ
0 -1.1116 TD
[(ou)20.8(t)-318(o)0(v)20.8(e)0(r)-314.4(a)-319(4)-323.6(t)0(o)-307.6(6)-317.9(we)13(ek)19.7(s)-317.7(p)0(e)19.7(r)0(i)15(o)0(d)-307.5(o)0(r)-313.2(j)0(u)20.7(s)0(t)-307.4(s)0(t)15.1(o)0(p)20.8(p)0(e)19.7(d)0(,)-309.8(a)0(n)19.7(d)-317.9(fu)15.1(ll)]TJ
T*
[(re)19.7(-e)19.7(va)19.7(lu)20.7(at)13.8(io)20.7(n)-358.2(s)0(h)15.3(o)0(u)20.8(l)0(d)-347.9(b)0(e)-354.7(c)0(a)18.5(r)0(r)20.9(i)0(e)19.6(d)-364(ou)20.8(t)-364.1(a)0(f)19.7(t)0(e)19.6(r)-358.2(4)-364(w)0(e)18.8(e)0(k)19.7(s)0(,)-349.9(c)0(o)13.9(n)0(-)]TJ
0 -1.1174 TD
[(si)20.9(st)20.9(in)15(g)-317.9(o)0(f)-319(\()0(a)19.7(t)-323.8(le)19.6(as)19.9(t\))-313.3(fT)19.7(4)-323.6(a)0(n)19.7(d)-323.6(TS)14(H)-318.7(m)0(e)18.4(a)0(s)14.1(u)0(r)20.9(e)0(m)18.5(e)0(n)19.7(t)0(.)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 72 584.6172 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 583.3132 Tm
[(If)-1044.6(primary)-1052.7(hypothyroidism)-1047.8(is)-1050.4(conrmed)-1048.9(\(TSH)]TJ
/F4 1 Tf
0 -1.1116 TD
()Tj
/F3 1 Tf
.5529 0 TD
[(10)-163.5(mU/L\),)-381(consider)-373.9(thyroid)-376.6(imaging)-379(and,)-376.5(if)-370.9(possible,)]TJ
-.5529 -1.1174 TD
[(genetic)-374.3(testing;)-373.2(if)-376.7(central)-374.3(CH)-372.7(is)-376.5(likely)-371(\(fT4)-374.2(below)-376.3(the)]TJ
0 -1.1116 TD
[(lower)-503(limit)-502.6(of)-503.3(the)-499.9(reference)-505.2(interval)-506.8(in)-503.4(combination)]TJ
T*
[(with)-593(a)-589.7(low)-597.5(normal)-590.8(of)-595.4(only)-592(mildly)-595.7(elevated)-595.5(TSH\),)]TJ
0 -1.1174 TD
[(consider)-477.6(evaluating)-481.4(the)-476.9(other)-473.3(anterior)-477.9(pituitary)-478.1(func-)]TJ
0 -1.1116 TD
[(tions)-333.9(and)-332.8(genetic)-339.8(testing.)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 72 507.9117 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 506.6077 Tm
.0073 Tc
[(If)-408.5(TS)-5.2(H)-403.6(i)-5.4(s)-402.5(a)-.7(b)-5.3(o)-5.3(v).4(e)-403.9(t)-5.4(he)-409.7(up)-5.3(pe)-6.5(r)-402.7(l)-5.4(im)-6.5(it)-408.6(of)-408.5(th)-5.3(e)-403.9(r).5(e)-6.5(f)-5.3(er)-5.3(en)-5.3(ce)-409.7(in)-5.3(-)]TJ
T*
.0069 Tc
[(te)-6.9(rv)-5.7(a)-6.9(l)-368.7(bu)-5.7(t)]TJ
/F4 1 Tf
4.3947 0 TD
0 Tc
(<)Tj
/F3 1 Tf
.5645 0 TD
.0109 Tc
[(1)4(0)-168.7(mU/)3.9(L)-365.8(\(p)4(rimar)4.1(y)-364.6(CH\))-370.3(o)4(r)-364.5(f)-1.7(T4)-370.3(j)3.9(u)-1.7(s)4.2(t)-370.5(abo)4(v)-1.7(e)]TJ
-4.9591 -1.1174 TD
.0123 Tc
[(t)5.3(h)-.3(e)-318.3(l)-.4(ower)-317.1(li)5.3(mi)5.3(t)-323(o)5.4(f)-322.8(t)-.4(h)5.4(e)-324(r)5.5(e)-1.5(f)5.5(e)-1.5(rence)-324(i)5.3(nt)5.3(er)5.5(val)-317.2(\()-.3(cen)5.4(t)-.4(r)5.5(a)-1.5(l)-323(C)4.4(H\))5.5(,)]TJ
0 -1.1116 TD
.0131 Tc
[(t)6.1(h).5(e)5.1(n)-339.3(c)5.1(o).5(n)6.2(tin)6.2(ue)-334.7(w)5.4(ith)6.2(dr)6.3(aw)5.4(al)-333.7(an)6.2(d)-339.3(r)6.3(et)6.1(est)-333.7(i).4(n)-333.6(a)5.1(no)6.2(the)5.1(r)-339.3(3)-333.6(t)6.1(o)-339.3(4)]TJ
T*
.0114 Tc
[(weeks)-329.3(\(1/)]TJ
/F4 1 Tf
4.026 0 TD
.0124 Tc
(++)Tj
/F3 1 Tf
1.1231 0 TD
.0126 Tc
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 453.0896 Tm
0 Tc
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 451.7857 Tm
[(If)-353.5(a)-359.4(child)-358.3(with)-356.9(no)-353.5(permanent)-360.3(CH)-361.2(diagnosis)-356.5(and)-355.8(a)-359.4(GIS)]TJ
0 -1.1116 TD
[(requires)-333.6(an)-337.4(LT4)-334(dose)]TJ
/F4 1 Tf
9.0715 0 TD
(<)Tj
/F3 1 Tf
.5529 0 TD
(3)Tj
/F14 1 Tf
.6681 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
[(g/kg)-332.8(per)-332.7(day)-332.8(at)-337.6(the)-332.9(age)-333.9(of)-336.2(6)]TJ
-10.8455 -1.1116 TD
[(months,)-333.8(then)-334(re-evaluation)-336.1(can)-333.9(be)-331.7(done)-333.9(already)-333.8(at)-331.8(that)]TJ
0 -1.1174 TD
[(time)-335.4(\(1/)]TJ
/F4 1 Tf
3.237 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 409.266 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 407.9621 Tm
[(We)-282.1(recommend)-286.5(avoiding)-280.9(iodine)-284.5(as)-279.6(an)-285.6(antiseptic)-285.5(during)]TJ
0 -1.1116 TD
[(peri-)-329.3(and)-327(neonatal)-329.3(period,)-333.8(as)-325.7(it)-330.8(can)-328.2(cause)-331.3(transient)-329.2(CH)]TJ
0 -1.1174 TD
(\(1/)Tj
/F4 1 Tf
1.1116 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F12 1 Tf
8.9663 0 0 8.9663 72 363.4015 Tm
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 121.1527 363.4015 Tm
[(In)-198(recent)-200.3(years,)-195.3(the)-194.7(prevalence)-201.2(of)-198(transient)-196.7(CH)]TJ
-6.0074 -1.1116 TD
[(has)-332.6(steadily)-328.1(increased.)-334.7(In)-330.5(a)-330.6(number)-325.8(of)-330.5(studies,)-329(factors)-332.5(have)]TJ
T*
[(been)-340.8(identied)-340.8(that)-339.9(increase)-341.7(the)-344.4(likelihood)-335.2(of)-342(transient)-340.7(dis-)]TJ
0 -1.1174 TD
[(ease,)-299.1(such)-299.1(as)-296.9(sex)-298(\(more)-295.8(often)-294.8(in)-296.1(boys\))-299(\(132,133\),)-297.8(low)-292.3(birth-)]TJ
0 -1.1116 TD
[(weight)-550.3(\(134,135\),)-545.5(neonatal)-548.2(morbidity)-547.2(requiring)-546.9(intensive)]TJ
T*
[(care)-330.4(\(135\),)-325.7(race/ethnicity)-338.6(\(more)-324.6(often)-329.3(in)-330.6(nonwhite)-327.9(patients\))]TJ
T*
[(\(14\),)-267(and)-269.4(less)-270.3(severe)-269.1(CH)-269(at)-268.4(diagnosis)-270.1(\(assessed)-271.8(by)-267.1(screening)]TJ
0 -1.1174 TD
[(TSH,)-457.9(or)-457.2(diagnostic)-462.8(TSH)-454.5(or)-457.2(fT4\))-460.6(\(8,132,133,136141\).)-457.5(In)]TJ
0 -1.1116 TD
[(contrast,)-556(factors)-551.3(such)-552.5(as)-550.3(prematurity)-551.7(\(11,142,143\),)-551.2(other)]TJ
T*
[(congenital)-383.5(abnormalities)-376.4(\(141\),)-377.5(a)-376.6(family)-383.6(history)-376.4(of)-376.5(thyroid)]TJ
0 -1.1174 TD
[(disease)-310.4(\(142\),)-302.6(abnormal)-312(thyroid)-307.4(morphology)-306.1(\(thyroid)-302.8(hypo-)]TJ
0 -1.1116 TD
[(plasia)-245.1(at)-239.6(diagnosis\))-242.4(\(142\),)-245(TSH)-241.4(elevation)]TJ
/F4 1 Tf
16.6225 0 TD
(>)Tj
/F3 1 Tf
.5529 0 TD
[(10)-163.5(mU/L)-244(after)-244(the)]TJ
-17.1754 -1.1116 TD
[(age)-368.5(of)-359.3(1)-364(year)-369.6(\(when)-364.6(infants)-366(outgrow)-365.8(the)-361.7(LT4)-368.6(dose\),)-361.2(and)-367.3(a)]TJ
0 -1.1174 TD
[(higher)-341.9(LT4)-339.8(dose)-339.4(requirement)-345.3(at)-337.6(1)-335.2(t)0(o)-342.1(3)-335.2(years)-341.7(of)-342(age)-339.7(are)-339.7(as-)]TJ
0 -1.1116 TD
[(sociated)-473.1(with)-472.1(permanent)-475.5(CH)-470.6(\(with)-473.1(conicting)-474.3(results)-469.5(be-)]TJ
T*
[(tween)-221.9(studies)-216.1(for)-222.1(the)-217.7(factor)-216.3(dose)-218.5(requirement\))-225.5(\(132,133,136)]TJ
0 -1.1174 TD
[(140,143147\).)-393.3(Recent)-397.2(studies)-388.9(have)-392.6(shown)-392.1(that)-397.5(early)-393.8(treat-)]TJ
0 -1.1116 TD
[(ment)-289.2(withdrawal)-286.2(to)-284.6(assess)-290.4(the)-286.8(necessity)-289.7(of)-284.4(further)-285.4(treatment)]TJ
T*
[(can)-195.7(be)-187.7(considered)-198.7(and)-188.8(done)-195.6(from)-189.9(the)-194.7(age)-189.9(of)-192.2(6)-191.2(months)-192.1(onward,)]TJ
T*
[(particularly)-408.8(in)-411.3(patients)-408.7(with)-403(a)-411.2(GIS,)-404.8(a)-405.4(negative)-410(rst-degree)]TJ
0 -1.1174 TD
[(family)-297.2(history)-295.7(of)-295.9(CH,)-301.3(or)-290.2(in)-296.1(those)-300.3(requiring)-299.3(a)-296(low)-292.3(LT4)-299.4(dose.)]TJ
0 -1.1116 TD
(Saba)Tj
/F5 1 Tf
2.2002 0 TD
[(et)-251.2(al.)]TJ
/F3 1 Tf
2.2636 0 TD
[(\(148\))-253.1(investigated)-258.9(92)-249.9(patients)-253.2(with)-253.2(CH)-257.5(and)-252.1(a)-249.9(GIS)]TJ
-4.4638 -1.1116 TD
[(and)-373.1(found)-374.1(49)-376.6(of)-376.5(them)-375.5(\(54%\))-375.1(to)-370.9(have)-375.4(transient)-381(CH.)-376.2(In)-370.8(this)]TJ
0 -1.1174 TD
[(study,)-435.1(the)-436.6(optimal)-436.7(LT4)-437.7(dose)-437.4(cut-off)-435.1(values)-435.1(for)-435.2(predicting)]TJ
0 -1.1116 TD
[(transient)-363.7(CH)-361.2(at)-366.4(the)-361.7(ages)-363.6(of)-359.3(6)-364(and)-361.6(12)-359.3(months)-364.9(were)-358.9(3.2)-362.7(and)]TJ
T*
(2.5)Tj
/F14 1 Tf
1.4169 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
[(g/kg)-298.3(per)-303.9(day,)-301.6(respectively,)-309.5(with)-299.3(a)-301.8(sensitivity)-307.3(of)-295.9(71%)-303.9(at)]TJ
-1.9698 -1.1174 TD
[(both)-194.6(time)-191.4(points,)-194.4(and)-194.5(a)-192.3(specicity)-198.8(of)-192.2(79%)-194.4(and)-194.5(78%)-188.7(at)-193.6(the)-194.7(ages)]TJ
0 -1.1116 TD
[(of)-365(6)-364(and)-361.6(12)-365.1(months,)-362.6(respectively)-369.4(\(with)-363.7(values)-366(below)-364.8(these)]TJ
T*
[(thresholds)-501.6(considered)-504(predictive)-498.7(of)-503.3(transient)-502(CH\).)-498.2(In)-497.5(the)]TJ
25.504 67.9242 TD
[(study)-299.2(by)-290.2(Oron)]TJ
/F5 1 Tf
6.1053 0 TD
[(et)-291.5(al.)]TJ
/F3 1 Tf
2.3442 0 TD
[(\(149\),)-296.9(17)-295.9(out)-291.4(of)-295.9(84)-295.9(patients)-293.6(with)-299.3(a)-290.2(GIS)]TJ
-8.4495 -1.1174 TD
[(\(20%\))-202.3(turned)-197.9(out)-199.3(to)-198.2(have)-196.8(transient)-202.5(CH.)-203.4(The)-195.7(optimal)-200.6(LT4)-201.5(dose)]TJ
0 -1.1116 TD
[(cut-of)-7.8(f)-243(values)-245(at)-245.4(the)-246.5(age)-247.5(of)-244.1(6)-243(months)-243.9(were)-249.5(2.2)]TJ
/F14 1 Tf
18.4944 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
[(g/kg)-240.7(per)-246.3(day,)]TJ
-19.0473 -1.1116 TD
[(with)-443.3(a)-440(sensitivity)-439.8(of)-439.9(90%)-436.3(and)-442.2(a)-440(specicity)-440.8(of)-439.9(57%.)-439.8(Both)]TJ
T*
[(studie)-7.8(s)-294.6(highlight)-292.7(the)-298.3(need)-300.5(for)-291.2(careful)-299.3(clinical)-300.8(and)-298.2(biological)]TJ
0 -1.1174 TD
[(monitoring)-231.5(to)-232.7(identify)-229.2(children)-230.2(who)-234.6(do)-226.8(not)-228.1(require)-234.7(long-term)]TJ
0 -1.1116 TD
(treatment.)Tj
1.0137 -1.1116 TD
[(Medication)-395.9(that)-391.7(interferes)-394.6(with)-397.2(thyroid)-388.1(function,)-393.8(in)-394(par-)]TJ
-1.0137 -1.1174 TD
[(ticular)-327.2(iodine)-319.1(and)-321.3(iodomimetics,)-327(may)-322.5(result)-318.8(in)-319.1(transient)-323.4(but)]TJ
0 -1.1116 TD
[(profou)-6.5(nd)-295.9(hypothyroidism)-299(\(150\).)-296.9(The)-299.4(use)-298(of)-295.9(iodine)-301.8(as)-296.9(a)-301.8(skin)]TJ
T*
[(antiseptic,)-242.9(such)-230(as)-239.3(povidoneiodine)-232.4(\(PVP-1\),)-236.2(is)-238.3(therefore)-238.1(not)]TJ
0 -1.1174 TD
[(recommended)-249.6(in)-238.5(obstetrics)-249.5(and)-240.6(neonatology,)-242.8(since)-243.9(it)-238.6(reaches)]TJ
0 -1.1116 TD
[(the)-350.2(fetal)-353.6(or)-347.7(neonatal)-352.4(thyroid)-353.5(gland)-346.6(easily,)-352.2(causing)-349.8(transient)]TJ
T*
[(hypothyroidism)-339.4(\(through)-331.4(skin)-332.6(and)-332.8(placenta)-336.3(in)-330.6(mothers,)-336(and)]TJ
T*
[(skin)-303.8(in)-296.1(neonates\))-307.1(\(29,151,152\).)-297.7(This)-299.3(may)-305.2(be)-297.1(more)-300.5(profound)]TJ
0 -1.1174 TD
[(in)-238.5(premature)-245.1(born)-240.5(babies,)-236.9(as)-239.3(escape)-247.2(from)-236(the)-240.7(Wolff)-238.2(Chaikoff)]TJ
0 -1.1116 TD
[(effect)-332.7(does)-327.9(not)-320.2(mature)-332.8(until)-322.7(term.)-327.1(Mothers)-326.5(should)-329.1(be)-325.9(asked)]TJ
T*
[(about)-444.5(consumption)-440.8(of)-439.9(iodine-rich)-441(nutritional)-440.1(food)-442.1(or)-439.9(sup-)]TJ
0 -1.1174 TD
[(plements,)-286.6(which)-284.1(can)-282.1(also)-282(induce)-279.8(transient)-283.1(CH)-280.6(\(153\).)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 313.0582 505.4172 Tm
[(3.5.)-502.8(Treatment)-263.6(and)-268.6(monitoring)-266(of)-260.7(pregnant)-268.2(women)]TJ
0 -1.2203 TD
[(with)-336.8(CH)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 462.8975 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 461.5936 Tm
[(In)-422.6(women)-423.5(with)-426(CH)-418.8(who)-424.6(are)-426.1(planning)-419.2(pregnancy,)-425.8(we)]TJ
0 -1.1116 TD
[(strongly)-308.3(recommend)-309.6(optimizati)-9.5(on)-301.7(of)-307.4(LT4)-311(treatment;)-310(in)]TJ
0 -1.1174 TD
[(addition,)-393.9(these)-393.7(women)-394.7(should)-392.4(be)-395(counseled)-399.2(regarding)]TJ
0 -1.1116 TD
[(the)-332.9(higher)-336.2(need)-335(for)-337.3(LT4)-334(during)-335(pregnancy)-335.9(\(1/)]TJ
/F4 1 Tf
18.8285 0 TD
(++)Tj
/F3 1 Tf
1.1001 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 419.0739 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 417.77 Tm
[(fT4)-344.3(\(or)-348.8(total)-346.9(T4\))-344.3(and)-344.3(TSH)-350.8(levels)-343.1(should)-346.4(be)-348.9(monitored)]TJ
0 -1.1174 TD
[(every)-382.2(4)-381.2(t)0(o)-376.7(6)-381.2(weeks)-382.9(during)-381.1(pregnancy,)-379.7(aiming)-383.6(at)-383.6(TSH)]TJ
0 -1.1116 TD
[(concentrations)-250.6(in)-244.2(accordance)-254.1(with)-241.7(current)-252(guidelines)-243.9(on)]TJ
T*
[(treatment)-326(of)-319(hypothyroidism)-327.9(during)-317.7(pregnancy,)-327.8(that)-322.6(is,)]TJ
/F4 1 Tf
T*
(<)Tj
/F3 1 Tf
.5529 0 TD
[(2.5)-166.9(mU/L)-261.3(throughout)-264.7(gestation)-260.1(in)-261.5(patients)-264.8(treated)-264.8(with)]TJ
-.5529 -1.1174 TD
[(LT4)-334(\(1/)]TJ
/F4 1 Tf
3.1794 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 353.3101 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 352.0062 Tm
[(In)-468.7(pregnant)-472(women)-469.6(with)-472.1(central)-472.2(CH,)-468.3(the)-471.1(LT4)-472.2(doses)]TJ
0 -1.1116 TD
[(should)-513.4(be)-510.2(increased)-521.3(aiming)-510.4(at)-516.1(an)-510.2(fT4)-511.3(concentration)]TJ
0 -1.1174 TD
[(above)-359.2(the)-350.2(mean/median)-359.3(value)-359.3(of)-353.5(the)-355.9(trimester-specic)]TJ
0 -1.1116 TD
[(reference)-338.2(interval)-339.8(\(1/)]TJ
/F4 1 Tf
8.5935 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
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T*
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[(cortica)-6.7(l)-541.3(morp)-5.5(hology)-546.9(among)-546.9(brain)-546.9(r).3(egi)-5.7(ons)-546.8(\(thinnin)-5.5(g)-541.2(or)]TJ
T*
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[(patial)-420.3(f)-5.4(unction)-420.1(\()-5.4(169,170\).)-422.5(I).4(n)-420.1(a)-.8(ddi)-5.6(tion,)-422.5(early)-420.1(epi)-5.6(s).5(odes)-419.9(o).3(f)]TJ
T*
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T*
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T*
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T*
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[(socioe)-6.6(ducational)-483.6(s).5(tatus)-483.3(\().4(71\))-483.5(and)-477.7(poor)-483.5(adheren)-5.4(c)-.8(e)-478.9(t).2(o)-477.7(t).2(he)]TJ
T*
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[(tive)-645.8(outcome)-645.8(and)-638.9(e)-.7(du)-5.3(cational)-644.8(a)-.7(ttaine)-6.5(m)5(e)-6.5(n).4(t.)-641.2(Therefo)-5.3(r).5(e,)]TJ
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[(psycho)-5.5(motor)-316.5(d).2(evel)-5.7(opment)-316.7(a)-.9(nd)-316.6(s)-5.3(c)-.9(hool)-316.7(pro)-5.5(g).2(ressi)-5.7(on)-316.6(should)]TJ
T*
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[(doubt,)-468.3(e)-.6(val)-5.4(u).5(ation)-466(b)-5.2(y)-466(a)-467.2(spec)-6.4(ialized)-466(t)-5.4(eam)-467.2(is)-465.8(ind)-5.2(i).4(cated)-466(at)]TJ
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[(speci)-5.4(c)-202.5(ages)-201.2(\()-5.5(12,)-203.7(18,)-203.7(24,)-203.7(and)-201.4(3).2(6)-207.1(m)-1(onths,)-203.7(5).2(,)-203.7(8).2(,)-203.7(a)-.9(nd)-201.4(1)-5.5(4)-201.4(years\))]TJ
T*
[(to)-472(mon)-5.4(itor)-471.9(p)-5.4(rogress)-5.2(i).2(on)-472(of)-477.7(speci)-5.6(c)-473.1(devel)-5.6(opmental)-477.9(s).5(kills)]TJ
T*
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[(\(58\).)-347(S)-4.7(peech)-350.4(delay,)-347(attention)-350.4(a)-.2(nd)-344.7(memory)-344.7(problems,)-347(and)]TJ
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T*
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[(than)-316.3(CH.)-312.8(U)-.3(ndi)-5.4(agnosed)-316.3(heari)-5.4(n).5(g)-310.5(i).4(mpa)-6.4(i).4(rment)-316.4(can)-310.5(a)-6.4(dversely)]TJ
T*
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T*
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T*
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T*
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T*
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T*
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T*
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[(able)-312.1(cause)-312.1(\().2(179182\).)-307.5(T)-1.1(herefore,)-307.5(T)-1.1(SH)-311.8(should)-305.1(b).1(e)-312.1(t)0(argeted)]TJ
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[(USfor)-471.7(example,)-474.1(every)-471.8(2)-477.5(to)-477.5(3)-471.8(y).5(earsin)-477.5(ch)6.3(ildren)-477.5(a)-.6(nd)]TJ
0 -1.1116 TD
.0185 Tc
[(adolescents)-368.3(with)-368.5(goitrous)-368.3(CH)-369.4(due)-369.7(to)-362.7(dyshormonogenesis)]TJ
T*
(\(including)Tj
/F5 1 Tf
4.7114 0 TD
.0189 Tc
(NIS)Tj
/F3 1 Tf
1.9583 0 TD
.0185 Tc
[(gene)-404.2(mutations\),)-405.4(to)-403.1(identify)-403.1(nodules)-402.9(that)]TJ
-6.6697 -1.1174 TD
[(may)-316.6(r).3(equire)-323.5(n)6(e)-323.5(n).2(eedle)-317.7(aspiration)-316.6(b).2(iopsy)-322.3(t).1(o)-316.6(r).3(ule)-317.7(out)-322.4(thy-)]TJ
0 -1.1116 TD
[(roid)-282.1(carcinoma.)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 62.022 307.0487 Tm
0 Tc
[(4.3.)-502.8(Growth,)-333.6(puberty,)-335.6(and)-331.9(fertility)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 275.4708 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 274.1668 Tm
[(Adequately)-568.6(treated)-564.4(children)-570.1(with)-564.2(nonsyndromic)-568.5(CH)]TJ
0 -1.1116 TD
[(have)-237.1(normal)-239.5(growth)-238(and)-240.6(puberty,)-237(and)-234.9(their)-243(fertility)-236.3(does)]TJ
0 -1.1174 TD
[(not)-452.7(differ)-451.3(from)-454.8(individuals)-451.3(who)-453.4(do)-451.5(not)-452.7(have)-450.2(CH)-453.4(\(1/)]TJ
/F4 1 Tf
0 -1.1116 TD
(+++)Tj
/F3 1 Tf
1.653 0 TD
(\).)Tj
/F12 1 Tf
8.9663 0 0 8.9663 72 209.9905 Tm
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 121.1527 209.9905 Tm
.0158 Tc
[(E)-3.8(a)2(rly)-388.5(a)2(nd)-388.5(adequately)-388.5(treated)-388.5(c)-3.7(h)3.2(ildren)-388.5(w)-3.4(i)3.1(th)]TJ
-6.0074 -1.1116 TD
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[(n)-5.4(ons)-5.2(yn)-5.4(dr)-5.3(omi)-5.5(c)-421.2(CH)-426.7(hav)-5.4(e)-421.2(no)-5.4(rm)-6.6(al)-420.2(g)-5.4(r).4(o)-5.4(w)-.5(th)-425.8(and)-425.8(p).4(u)-5.4(b).4(er)-5.3(ta)-6.5(l)-420.2(d).4(e)-6.5(-)]TJ
0 -1.1174 TD
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[(v)-5.6(e)-1(lo)-5.6(pme)-6.7(n).2(t)-316.7(\().2(1)-5.6(8).2(3)-5.6(18)-5.6(7\))-5.5(.)-313.2(A)-.7(d)-5.6(u).2(l)-5.7(t)-311(h)-5.6(e)-1(ig)-5.6(ht)-316.7(is)-316.4(no)-5.6(rm)-6.8(al)-311(a)-6.7(n).2(d)-316.6(c)-1(o)-5.6(m)-1(pa)-6.7(-)]TJ
0 -1.1116 TD
[(r)-5.5(a)-1(bl)-5.7(e)-404.2(w)-6.4(ith)-408.8(si)-5.7(bl)-5.7(ing)-5.6(s).4(,)-405.3(w)-6.4(it)-5.7(h)-403(n).2(o)-408.8(e)-1(f)-5.5(f).2(ec)-6.7(ts)-408.6(of)-403(s)-5.4(e)-1(v)-5.6(e)-1(r)-5.5(i).1(t)-5.7(y)-403(of)-408.7(CH)-403.9(a)-6.7(t)]TJ
T*
.013 Tc
[(d)-5.4(i).3(ag)-5.4(no)-5.4(si)-5.5(s,)-215.1(CH)-213.6(e)-6.5(tio)-5.4(lo)-5.4(gy)-5.4(,)-209.3(o)-5.4(r)-212.7(LT4)-212.7(s)-5.2(t).3(a)-6.5(r).4(t)-5.5(i).3(n)-5.4(g)-212.7(dos)-5.2(e)-213.9(\().4(4)-5.4(7).4(,1)-5.4(83)-5.4(18)-5.4(5\))-5.3(;)]TJ
T*
[(mo)-5.5(re)-6.6(ove)-6.6(r,)-232.4(i)-5.6(n)-230.1(t)-5.6(h).3(e)-231.3(m)-6.7(ajo)-5.5(r).3(i)-5.6(t).2(y)-235.9(o).3(f)-230.1(c)-6.6(hi)-5.6(ldr)-5.4(e)-.9(n)-5.5(,)-232.4(ad)-5.5(ult)-236(h).3(e)-6.6(i).2(gh)-5.5(t)-230.2(i)-5.6(s)-229.9(a)-6.6(bov)-5.5(e)]TJ
0 -1.1174 TD
.0132 Tc
[(t)-5.3(h).6(e)-536.2(t).5(a)-6.3(r).6(g)-5.2(e)-.6(t)-535.2(h)-5.2(eig)-5.2(h).6(t)-535.2(i)-5.3(n)-535.1(b).6(o)-5.2(t).5(h)-535.1(s)-5(ex)-5.2(es)-534.9(\()-5.1(4).6(7)-5.2(,)-1.7(18)-5.2(3,18)-5.2(4\))-5.1(.)-531.6(O)-6(ns)-5(et)-535.2(o)-5.2(f)]TJ
0 -1.1116 TD
.013 Tc
[(p)-5.4(ube)-6.5(rt)-5.5(y)-385.5(o)-5.4(cc)-6.5(urs)-391.1(a)-6.5(t)-385.6(t)-5.5(h).4(e)-392.4(n).4(o)-5.4(r).4(ma)-6.5(l)-391.4(a)-.8(ge)-392.4(in)-391.3(t)-5.5(h).4(e)-392.4(v).4(as)-5.2(t)-391.4(maj)-5.5(or)-5.3(it)-5.5(y)-385.5(o)-5.4(f)]TJ
T*
[(CH)-737.7(p)-5.4(a)-.8(t)-5.5(i).3(en)-5.4(ts)-736.7(a)-6.5(n).4(d)-736.9(p)-5.4(ro)-5.4(gre)-6.5(ss)-5.2(es)-736.7(n)-5.4(o).4(r)-5.3(mal)-5.5(ly)-736.9(i)-5.5(n)-736.9(bo)-5.4(th)-736.9(se)-6.5(xe)-6.5(s)]TJ
0 -1.1174 TD
.0132 Tc
[(\()-5.1(47,1)-5.2(8).6(3)-5.2(,)-1.7(11)-5.2(4\).)-439.5(Th)-5.2(e)-438.3(s).8(a)-6.3(m)-.6(e)-438.3(a)-.6(p)-5.2(p).6(l)-5.3(i).5(es)-442.7(to)-437.2(ag)-5.2(e)-438.3(a)-.6(t)-437.3(m)-.6(e)-6.3(n).6(a)-6.3(r).6(c)-6.3(h).6(e)-438.3(a)-.6(n)-5.2(d)]TJ
0 -1.1116 TD
[(me)-6.4(ns)-5.1(tr)-5.2(ual)-281.9(c)-6.4(ycl)-5.4(e)-.7(s)-281.5(\()-5.2(11)-5.3(4,18)-5.3(3\))-5.2(.)-278.3(I)-5.2(n)-281.7(a)-.7(du)-5.3(lt)-5.4(s,)-284.1(fer)-5.2(t).4(i)-5.4(l).4(i)-5.4(t).4(y)-281.7(i).4(s)-281.5(g)-5.3(en)-5.3(er)-5.2(all)-5.4(y)]TJ
T*
[(n)-5.2(orm)-6.4(al)-299(\()-5.1(1).6(8)-5.2(8\).)-301.3(H)-6(o).6(we)-6.3(ve)-6.3(r,)-301.2(wo)-5.2(men)-298.9(w)-6(i).5(t)-5.3(h)-298.9(CH)-299.8(m)-6.4(a)-.6(y)-298.9(h).6(a)-6.3(v).6(e)-300.1(a)-6.3(n)-298.9(i).5(n)-5.2(-)]TJ
0 -1.1174 TD
.0129 Tc
[(cr)-5.4(ea)-6.6(se)-6.6(d)-356.8(r)-5.4(is)-5.3(k)-362.6(o).3(f)-362.5(a)-6.6(dve)-6.6(rs)-5.3(e)-363.7(pre)-6.6(gn)-5.5(anc)-6.6(y)-362.6(ou)-5.5(tco)-5.5(mes)-5.3(.)-359.2(I)-5.4(n)-362.6(a)-.9(d)-5.5(d).3(it)-5.6(io)-5.5(n,)]TJ
0 -1.1116 TD
[(t)-5.5(h).4(ei)-5.5(r)-253(o).4(f)-5.3(f).4(s)-5.2(p).4(r)-5.3(i).3(ng)-253(i)-5.5(s)-252.8(at)-253.2(r)-5.3(i).3(s)-5.2(k)-247.3(f)-5.3(o).4(r)-253(p)-5.4(oo)-5.4(rer)-253(m)-6.6(ot)-5.5(or)-253(co)-5.4(or)-5.3(din)-5.4(a)-.8(t)-5.5(i).3(o)-5.4(n)-247.3(\()-5.3(s).6(e)-6.5(e)]TJ
T*
.2948 Tc
[(a)281(l)276.3(s)282.4(o)0(S)276.6(e)281(c)275.3(t)282.1(i)276.3(o)282.2(n3)282.2(.)279.9(5)276.4(\)\()282.2(1)276.4(5)282.2(4)276.4(,)279.9(1)282.2(5)276.4(6)282.2(\))276.5(.)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 313.0582 725.7825 Tm
0 Tc
[(4.4.)-502.8(Bone,)-338.2(metabolic,)-334.7(and)-331.9(cardiovascular)-334.5(health)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 694.2045 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 692.9006 Tm
[(Adequately)-568.6(treated)-570.1(children)-564.3(with)-570(nonsyndromic)-562.7(CH)]TJ
0 -1.1116 TD
[(also)-385.6(have)-386.9(normal)-383.5(bone,)-383.4(metabolic,)-387.1(and)-384.6(cardiovascular)]TJ
0 -1.1174 TD
[(health)-337.5(\(1/)]TJ
/F4 1 Tf
3.9051 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F12 1 Tf
8.9663 0 0 8.9663 323.0361 635.0172 Tm
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 372.2456 635.0172 Tm
[(Thyroid)-360.3(hormones)-368.1(play)-362.8(an)-366.2(important)-364(role)-362.8(in)]TJ
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[(skeletal)-525.1(growth)-520.2(and)-517.1(bone)-518.2(mineral)-524.1(homeostasis.)-519.9(At)-515.8(birth,)]TJ
0 -1.1174 TD
[(skeletal)-265.9(maturation)-256.8(is)-261.3(delayed)-259(in)-255.8(the)-258(majority)-259.2(of)-255.6(CH)-257.5(patients)]TJ
0 -1.1116 TD
[(with)-379.9(severe)-372.7(hypothyroidism)-379.7(\(70\);)-374.2(however,)-377.2(within)-370.7(the)-373.2(rst)]TJ
T*
[(months)-295.8(of)-295.9(life,)-291.5(LT4)-293.7(treatment)-297.2(rapidly)-297.1(normalizes)-298(bone)-293.6(mat-)]TJ
0 -1.1174 TD
[(uration)-320.1(\(71\).)-318.8(Since)-318.8(thyroid)-319(hormones)-322(have)-317.8(major)-319(effects)-322.1(on)]TJ
0 -1.1116 TD
[(bone)-541.2(remodeling,)-548.1(LT4)-535.6(overtreatm)-10.2(ent)-540.2(may)-535.6(increase)-549(bone)]TJ
T*
[(turnov)-6.7(er)-291.3(with)-293.5(higher)-290.1(bone)-293.6(resorption)-294.4(than)-293.7(formation,)-292.4(result-)]TJ
0 -1.1174 TD
[(ing)-279.9(in)-273(progressive)-279.1(bone)-276.3(loss)-280.6(\(189\).)-273.8(Yet,)-279.6(long-term)-277.4(studies)-273.7(in)]TJ
0 -1.1116 TD
[(children)-247.5(and)-246.4(young)-247.4(adults)-244(with)-247.4(CH)-246(have)-242.9(shown)-248.1(normal)-245.3(bone)]TJ
T*
[(mineral)-288(density)-285.4(\(190193\),)-284(suggesting)-282.8(that)-288.1(early)-284.4(started)-286.5(and)]TJ
T*
[(adequ)-7.8(ate)-241.9(LT4)-241.8(treatment)-245.4(is)-244(not)-239.6(harmful)-246.3(to)-244.2(bone)-241.7(health.)-243(Given)]TJ
0 -1.1174 TD
[(the)-194.7(importance)-200.3(of)-192.2(sufcient)-196.4(calcium)-197(intake,)-191.2(patients)-195.6(with)-195.6(CH,)]TJ
0 -1.1116 TD
[(in)-296.1(addition)-298.4(to)-290.3(adequate)-301.6(LT4)-293.7(treatment,)-300.7(should)-294.5(consume)-299.1(800)]TJ
T*
[(to)-347.9(1200)-165.7(mg)-349(calcium)-346.7(daily;)-348(if)-347.9(dietary)-350.1(calcium)-346.7(intake)-349(is)-347.7(low,)]TJ
0 -1.1174 TD
[(supple)-7.7(ments)-278.5(should)-283(be)-279.8(added)-284.3(\(1,190\).)]TJ
1.0137 -1.1116 TD
[(Body)-235.8(mass)-236.8(index)-237.2(and)-234.8(composition)-239.3(are)-241.7(generally)-238.3(normal)-233.7(in)]TJ
-1.0137 -1.1116 TD
[(children)-195.7(and)-194.5(adult)-197(with)-189.8(CH)-194.2(\(90,91,187\),)-198.7(and)-188.8(comparable)-201.3(with)]TJ
0 -1.1174 TD
[(that)-437.8(of)-439.9(the)-436.6(general)-437.5(population.)-436.5(However,)-441.4(earlier)-437.6(adiposity)]TJ
0 -1.1116 TD
[(rebound)-308.3(\(194196\))-309.4(and)-309.7(increased)-308.2(risks)-310.5(of)-307.4(being)-306.3(overweight)]TJ
T*
[(or)-359.3(obese)-359(have)-358.1(been)-358.1(reported)-356.8(in)-359.4(up)-353.5(to)-353.7(37%)-361.5(of)-353.5(young)-356.9(adults)]TJ
0 -1.1174 TD
[(with)-362.6(CH)-361.2(\(47,71,114\).)-360(Therefore,)-363.5(lifestyle)-363.9(interventions,)-360.2(in-)]TJ
0 -1.1116 TD
[(cluding)-308.6(diet)-299.6(and)-304(physical)-305(exercise,)-304.8(should)-306(be)-302.9(encouraged)-303.6(to)]TJ
T*
[(avoid)-283.3(metabolic)-285.7(abnormalities)-284.3(\(1\).)]TJ
1.0137 -1.1116 TD
[(In)-244.1(addition)-252.3(to)-244.2(an)-245.3(increased)-250.6(risk)-246.2(of)-244.1(congenital)-251(heart)-244.1(disease)]TJ
-1.0137 -1.1174 TD
[(\(8688\),)-437.3(neonates)-438.5(with)-437.5(untreated)-434.1(CH)-436.1(may)-437.7(have)-438.7(increased)]TJ
0 -1.1116 TD
[(aortic)-608.2(intimal-media)-608.4(thickness)-611.1(\(IMT\),)-604.2(serum)-606.7(cholesterol)]TJ
T*
[(levels)-464(\(197\),)-463.9(and)-465.2(impaired)-461.8(cardiac)-467.5(function)-459.5(\(198,199\))-461.4(re-)]TJ
0 -1.1174 TD
[(versed)-285.2(by)-278.7(early)-284.4(LT4)-282.2(treatment)-285.7(\(200\).)]TJ
1.0137 -1.1116 TD
[(Young)-352(adults)-347.7(with)-345.4(CH)-349.7(have)-352.3(normal)-348.9(blood)-345.5(pressure,)-353.9(glu-)]TJ
-1.0137 -1.1116 TD
[(cose,)-620.5(and)-609.2(lipid)-616.4(metabolism,)-618.5(and)-609.2(carotid)-620.8(IMT)-610.1(\(90,200\).)]TJ
0 -1.1174 TD
[(Howev)-8.4(er,)-467.5(repeated)-468.6(episodes)-471.7(of)-462.9(inadequate)-476.7(treatment)-470(may)]TJ
0 -1.1116 TD
[(place)-291.4(them)-283.4(at)-291.5(risk)-280.8(of)-290.2(subtle)-284.3(cardiovascular)-291.9(dysfunction)-289.8(such)]TJ
T*
[(as)-487(low)-482.4(exercise)-485.7(capacity,)-489.5(impaired)-484.9(diastolic)-484.9(function,)-480.2(in-)]TJ
T*
[(creased)-300.1(IMT,)-296.8(and)-298.2(mild)-293.9(endothelial)-298.4(dysfunction)-295.5(\(201\).)-296.9(Whe-)]TJ
0 -1.1174 TD
[(ther)-328.2(these)-324.5(subtle)-330.4(abnormalities)-324.6(result)-330.4(in)-324.9(impaired)-323.6(quality)-326(of)]TJ
0 -1.1116 TD
[(life)-247.7(or)-244.1(in)-250(an)-245.3(increased)-244.9(risk)-246.2(of)-244.1(cardiovascu)-10.9(lar)-240.7(disease)-252.8(needs)-243.8(to)]TJ
T*
[(be)-251(further)-256.6(claried.)-251.9(Anyway,)-254.9(good)-246.3(adherence)-257.6(to)-250(treatment)-251.1(in)]TJ
0 -1.1174 TD
[(adole)-8(scents)-302.4(and)-298.2(young)-299.3(adults)-301.6(with)-299.3(CH)-303.6(is)-301.6(mandatory)-301.6(for)-297(op-)]TJ
0 -1.1116 TD
[(timal)-284.8(metabolic)-285.7(and)-280.9(cardiovascular)-286.2(health.)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 313.0582 177.1086 Tm
[(4.5.)-502.8(Patient)-336.3(and)-331.9(professional)-341(education,)]TJ
0 -1.2203 TD
[(adherence,)-340.4(and)-331.9(health-related)-337.7(quality)-332.8(of)-336.6(life)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 134.5889 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 133.285 Tm
[(Medical)-300.4(education)-301.6(about)-294.8(CH)-297.8(should)-294.5(be)-297.1(improved)-299.3(at)-297.2(all)]TJ
0 -1.1116 TD
[(levels,)-335(with)-339.6(regular)-332.6(updates)-338.3(\(1/)]TJ
/F4 1 Tf
12.729 0 TD
(+++)Tj
/F3 1 Tf
1.6588 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 112.6488 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 111.3448 Tm
[(Education)-388.1(of)-382.3(parents,)-382(starting)-384.5(at)-383.6(the)-384.7(time)-381.4(of)-382.3(the)-384.7(diag-)]TJ
0 -1.1116 TD
[(nosis,)-360(and)-361.6(later)-359.4(on)-359.3(of)-365(the)-355.9(patient,)-365.2(is)-359.2(essential)-364.7(not)-360.5(only)]TJ
T*
[(throughout)-610.3(childhood,)-608(but)-602.4(also)-610.3(during)-605.7(transition)-605.7(to)]TJ
0 -1.1174 TD
[(adult)-335.2(care)-336.2(and)-332.8(in)-336.4(women)-337.1(during)-335(pregnancy)-335.9(\(1/)]TJ
/F4 1 Tf
19.1049 0 TD
(+++)Tj
/F3 1 Tf
1.6588 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 68.8252 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 67.5212 Tm
[(Since)-468.6(adherence)-465(to)-463.1(treatment)-470(may)-460.7(inuence)-467.3(the)-465.4(out-)]TJ
0 -1.1116 TD
[(comes,)-334.8(it)-336.5(should)-334.8(be)-331.7(promoted)-339.6(throughout)-333.8(life)-334.1(\(1/)]TJ
/F4 1 Tf
20.0265 0 TD
(++)Tj
/F3 1 Tf
1.1001 0 TD
(0\).)Tj
/F6 1 Tf
8.9663 0 0 8.9663 62.022 749.6502 Tm
(402)Tj
40.9535 0 TD
[(VAN)-332.3(TROTSENBURG)-337.1(ET)-338.7(AL.)]TJ
ET
endstream
endobj
181 0 obj
<>stream
/GS1 gs
BT
/F12 1 Tf
8.9663 0 0 8.9663 69.7323 725.7825 Tm
0 0 0 rg
0 Tc
0 Tw
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 118.9417 725.7825 Tm
[(It)-342.1(is)-342(very)-345.4(clear,)-346.6(and)-344.3(it)-342.3(should)-340.6(not)-343.3(have)-346.6(to)-342.1(be)]TJ
-6.0131 -1.1116 TD
[(stated)-487(here,)-482.4(that)-478.1(medical)-485(professionals)-488.6(should)-478.8(have)-484.8(basic)]TJ
0 -1.1174 TD
[(knowledge)-358.8(about)-358.1(CH.)-358.9(The)-357(education)-359.2(of)-353.5(parents,)-359(starting)-355.7(at)]TJ
0 -1.1116 TD
[(diagnosis)-748.2(and)-747.5(updated)-747.4(regularly,)-747.4(and)-747.5(of)-745.2(CH)-747.1(patients)]TJ
T*
[(throughout)-328(childhood)-328.1(is)-324.7(mandatory.)-328(Good)-322.1(understanding)-327.7(of)]TJ
0 -1.1174 TD
[(CH)-355.4(is)-353.5(essential)-359(to)-353.7(manage)-356.9(parental)-352.4(anxiety)-355.9(attitude,)-360.7(and)-350(to)]TJ
0 -1.1116 TD
[(promote)-655.3(treatment)-654.3(adherence)-655(throughout)-656.3(life.)-648.6(Both)-650.7(are)]TJ
T*
[(important)-519.5(conditions)-513.5(to)-514.9(assure)-515.4(optimal)-517.3(outcomes)-513.4(in)-514.9(CH.)]TJ
0 -1.1174 TD
[(Adequate)-289.8(education)-290.1(of)-278.6(patients)-287.8(is)-284.4(also)-287.7(important)-283.4(to)-284.5(improve)]TJ
0 -1.1116 TD
[(self-esteem)-323.1(and)-309.7(health-related)-321.2(quality)-314.5(of)-313.2(life)-311.1(\(HRQoL\),)-314.6(and)]TJ
T*
[(to)-497.7(assure)-503.8(treatment)-504.6(adherence)-499.5(particularly)-506.7(during)-496.3(adoles-)]TJ
T*
[(cence)-234.8(and)-234.9(pregnancy.)-229.9(The)-230.3(perce)-9(ption)-230.4(of)-226.8(the)-235(impact)-229.3(of)-232.6(CH)-228.7(on)]TJ
0 -1.1174 TD
[(behavior)-385.6(varies)-389(with)-379.9(age)-385.8(and)-384.6(differs)-383.1(between)-386.6(children)-385.7(and)]TJ
0 -1.1116 TD
[(their)-243(parents)-246.1(\(202\).)-239.3(Most)-241.4(\(71,203,204\),)-245.9(but)-239.6(not)-239.6(all)-240.9(\(202,205\),)]TJ
T*
[(studies)-262.2(suggest)-256.3(that)-259.3(children)-259(and)-252.1(young)-258.9(adults)-255.5(with)-259(CH)-257.5(have)]TJ
0 -1.1174 TD
[(an)-187.7(increased)-193(risk)-182.9(for)-187.5(lower)-186.2(HRQoL.)-191.5(Young)-184.9(adults)-186.4(with)-189.8(CH)-182.7(do)]TJ
0 -1.1116 TD
[(not)-331.7(report)-324.6(problems)-333.7(concerning)-331.4(autonomy)-328.1(and)-327(sexual)-331.4(func-)]TJ
T*
[(tioning.)-472.3(However,)-470.2(compared)-474.3(with)-472.1(the)-465.4(general)-472.1(population,)]TJ
0 -1.1174 TD
[(they)-264.9(experience)-270.4(lower)-266.8(HRQoL)-268.7(with)-264.7(respect)-270.3(to)-261.5(cognitive)-266.1(and)]TJ
0 -1.1116 TD
[(social)-297(functioning,)-293.5(daily)-294.9(activities,)-294.9(aggressiveness,)-299.3(and)-292.4(self-)]TJ
T*
[(worth)-311.7(\(204\),)-314.1(which)-307.2(was)-316.2(already)-310.8(present)-315.2(in)-307.6(childhood)-310.8(\(203\).)]TJ
T*
[(Moreover,)-366.8(young)-368.4(adults)-364.9(with)-362.6(CH)-367(are)-362.7(more)-363.9(likely)-365.3(to)-365.2(report)]TJ
0 -1.1174 TD
[(associated)-672.1(chronic)-672.5(diseases,)-671.9(hearing)-666.7(impairment,)-670.4(visual)]TJ
0 -1.1116 TD
[(problems,)-308.3(and)-309.7(overweight)-308.2(than)-305.2(their)-312.2(peers.)-304.8(Fewer)-308(attain)-308.8(the)]TJ
T*
[(highest)-337.2(socioeconomic)-342.8(category)-340.7(and)-332.8(full-time)-341.1(employment,)]TJ
0 -1.1174 TD
[(and)-367.3(more)-363.9(are)-368.5(still)-362.9(living)-364.1(with)-362.6(their)-369.8(parents.)-364.7(CH)-361.2(severi)-8.8(ty)-359.4(at)]TJ
0 -1.1116 TD
[(diagnosis,)-210.2(long-term)-208.3(treatment)-210.8(adequacy,)-207(and)-206.1(the)-206.2(presence)-209.1(of)]TJ
T*
[(other)-358.1(chronic)-361.5(health)-360.5(conditions)-358(seem)-359.1(to)-353.7(be)-360.5(the)-355.9(main)-358.3(deter-)]TJ
0 -1.1174 TD
[(minants)-211.8(of)-203.8(educationa)-10.2(l)-202.8(achievement)-215.3(and)-206.1(HRQoL)-211.1(scores.)-207.8(Yet,)]TJ
0 -1.1116 TD
[(despite)-355.7(these)-359.1(subtle)-353.4(disadvantages,)-356.3(most)-356.9(patients)-351.2(well)-358(inte-)]TJ
T*
[(grated)-285.5(into)-281.1(society)-280.8(\(71\).)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 59.7543 371.3385 Tm
[(4.6.)-502.8(Transition)-338.5(to)-330.2(adult)-337.5(care)]TJ
/F12 1 Tf
1.1128 -1.8273 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 69.7323 339.7605 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 78.633 338.5133 Tm
[(When)-434.1(patients)-431.8(are)-437.6(transferred)-435.9(from)-431.8(pediatric)-434.2(to)-434.3(adult)]TJ
0 -1.1174 TD
[(care,)-449(the)-448.1(main)-450.4(aims)-444.5(are)-449.1(continuity)-450.4(of)-445.7(care)-451.4(and,)-451.4(with)]TJ
0 -1.1116 TD
[(that,)-326(optimal)-333(clinical)-329.6(outcomes)-329.1(and)-327(quality)-331.8(of)-324.7(life,)-326(and)]TJ
T*
[(to)-549.5(increase)-549(understanding)-552.3(of)-549.3(CH)-545.5(and)-551.6(promote)-551.6(self-)]TJ
0 -1.1174 TD
[(management)-340.8(\(1/)]TJ
/F4 1 Tf
6.5833 0 TD
(+++)Tj
/F3 1 Tf
1.6588 0 TD
(\).)Tj
/F12 1 Tf
8.9663 0 0 8.9663 69.7323 263.5086 Tm
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 118.9417 263.5086 Tm
[(The)-178.5(period)-186.4(of)-180.7(transition)-185.3(from)-184.1(pediatric)-186.5(to)-180.9(adult)]TJ
-6.0131 -1.1116 TD
[(care)-439.8(can)-431.8(be)-435.3(challenging)-436.5(since)-434(it)-428.7(is)-434.1(associated)-436(with)-437.5(an)-429.6(in-)]TJ
T*
[(creased)-415.3(risk)-413.2(of)-411.1(poor)-413.3(treatment)-412.4(compliance)-414.6(and)-413.4(inadequate)]TJ
0 -1.1174 TD
[(follow-up)-241.4(that)-230.5(may)-236.1(have)-237.1(repercussions,)-239.6(in)-232.7(terms)-238.2(of)-232.6(increased)]TJ
0 -1.1116 TD
[(morbidity,)-757.9(and)-759(poor)-753.1(educational)-760.2(and)-753.2(social)-757.8(outcomes)]TJ
T*
[(\(206,207\).)-476.4(Family)-469.9(structure)-478.8(and)-471(parental)-479.1(involvement)-471.1(are)]TJ
T*
[(important)-306.4(for)-297(preventing)-307.3(and)-298.2(tackling)-305.3(this)-304(problem.)-301.6(Finally,)]TJ
0 -1.1174 TD
[(given)-352.4(the)-344.4(female)-351.2(preponderance)-348.4(in)-347.9(all)-350.3(thyroid)-347.8(diseases)-345.9(and)]TJ
0 -1.1116 TD
[(the)-379(nding)-375.2(that)-374.4(\(subclinical\))-380.9(hypothyroidism)-379.7(may)-374.3(be)-377.7(asso-)]TJ
T*
[(ciated)-275.3(with)-270.5(subfertility)-274(and)-275.2(adverse)-275.9(pregnancy)-272.6(and)-269.4(offspring)]TJ
0 -1.1174 TD
[(outcomes,)-292.2(impro)-6.8(vement)-286.8(and)-292.4(maintenance)-295.9(of)-290.2(disease)-293.2(control)]TJ
0 -1.1116 TD
[(in)-284.6(young)-276.2(women)-285.2(are)-282.1(crucial)-282.1(\(154,156\).)]TJ
/F6 1 Tf
8.9663 0 0 8.9663 59.7543 117.3543 Tm
[(5.)-501.1(GENETICS)-340.4(OF)-331.2(CH,)-338(GENETIC)-336.1(COUNSELING,)]TJ
0 -1.2266 TD
[(AND)-337.2(ANTENATAL)-338.8(MANAGEMENT)]TJ
/F3 1 Tf
9.843 0 0 9.843 69.6189 89.4614 Tm
[(5.1.)-498.6(Criteria)-340.8(for)-331.5(genetic)-339.8(counseling)]TJ
0 -1.1174 TD
[(5.2.)-498.6(Genetics)-341.5(of)-330.5(CH)]TJ
0 -1.1116 TD
[(5.3.)-498.6(Antenatal)-590.6(diagnostics,)-588.1(evaluation)-585.1(of)-583.9(fetal)-584(thyroid)]TJ
1.9986 -1.1116 TD
[(function,)-336.2(and)-338.5(management)-335.1(of)-336.2(fetal)-336.4(hypothyroidism)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 310.8472 725.7825 Tm
[(5.1.)-496.4(Criteria)-338.4(for)-330.9(genetic)-340(counseling)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 320.8251 694.2045 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 329.6692 692.9006 Tm
[(Genetic)-668.9(counseling)-670(should)-663.2(be)-660(targeted)-669.1(rather)-665.6(than)]TJ
0 -1.1116 TD
[(general)-449(\(to)-446.9(all)-448.2(CH)-447.6(patients\),)-447.8(and)-448(done)-449.1(by)-445.7(an)-441.1(experi-)]TJ
0 -1.1174 TD
[(enced)-337.3(professional)-337.9(\(2/)]TJ
/F4 1 Tf
9.0255 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 320.8251 661.3226 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 329.6692 660.0187 Tm
[(Counseling)-410.7(should)-409.7(include)-407.7(explaining)-405.4(inheritance)-414.6(and)]TJ
0 -1.1116 TD
[(the)-258(risk)-257.7(of)-255.6(recurrence)-264.4(of)-255.6(the)-258(patients)-254.3(primary)-263.6(or)-255.6(central)]TJ
0 -1.1174 TD
[(form)-339.6(of)-330.5(CH,)-335.8(based)-341.7(on)-330.5(the)-338.7(CH)-332.4(subtype,)-334.8(the)-338.7(family)-337.5(his-)]TJ
0 -1.1116 TD
[(tory,)-336.2(and,)-336.2(if)-330.6(known,)-338.1(the)-332.9(\(genetic\))-336.1(cause)-337.1(\(1/)]TJ
/F4 1 Tf
17.6305 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 320.8251 617.499 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 329.6692 616.1951 Tm
[(Pa)14.1(re)19.7(nt)20.7(s)-225.5(w)0(i)14.1(t)0(h)-215.4(a)-226.9(ch)19.7(il)14.8(d,)-217.6(or)-215.3(fa)19.7(mi)19.5(li)20.6(es)-222(wi)19.8(th)-221.2(a)-226.9(m)0(e)18.4(m)0(b)19.6(e)0(r)-216.4(w)0(i)19.8(t)0(h)-221.2(C)0(H)18.9(,)]TJ
0 -1.1116 TD
[(sh)15.3(ou)20.8(ld)-336.4(ha)19.7(ve)-343.2(ac)18.5(ce)18.5(ss)-335.9(to)-342.1(in)20.7(fo)20.9(rm)19.7(at)19.5(io)15(n)-346.7(a)0(b)19.7(o)0(u)20.8(t)-346.8(th)15(e)-347.8(t)0(w)19.8(o)-346.7(ma)18.4(jo)20.7(r)]TJ
0 -1.1174 TD
[(fo)15.1(rm)19.6(s)-450.2(o)0(f)-439.9(p)0(r)20.9(i)0(m)19.5(a)0(r)14(y)-450.4(CH)18.9(T)18.5(D)-451.2(a)0(n)19.7(d)-450.3(dy)20.8(sh)21(or)15.1(mo)19.6(no)20.8(ge)19.7(ne)19.7(si)20.9(s)]TJ
0 -1.1116 TD
[(an)13.9(d,)-304(if)-307.6(in)20.7(cl)19.5(ud)20.8(ed)-308.6(in)-301.8(th)20.7(e)-319(n)0(e)19.7(o)0(n)20.8(a)0(t)19.5(a)0(l)-308.8(s)0(c)19.9(r)0(e)14(e)0(n)19.7(i)0(n)20.7(g)0(,)-304(a)0(b)19.7(o)0(u)20.8(t)-318(ce)18.5(nt)20.7(ra)19.7(l)]TJ
T*
[(CH)-315.1(\(1)15.1(/)]TJ
/F4 1 Tf
2.7877 0 TD
[(++)21.2(+)]TJ
/F3 1 Tf
1.6242 0 TD
(\).)Tj
/F12 1 Tf
8.9663 0 0 8.9663 320.8251 545.7825 Tm
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 369.9778 545.7825 Tm
[(Genetic)-478.9(counseling)-474.2(is)-474.4(highly)-479.2(recommended)]TJ
-6.0074 -1.1116 TD
[(for)-400.7(patients)-403(and)-401.9(families)-404.2(with)-403(one)-401.9(or)-399.6(more)-398.4(affected)-405.2(mem-)]TJ
0 -1.1174 TD
[(ber\(s\))-283.9(with)-282(CH.)-284(Precise)-287.4(criteria)-289.1(were)-284(already)-287.8(established)-286.3(for)]TJ
0 -1.1116 TD
[(the)-332.9(CH)-332.4(consensus)-340(guideline)-335.2(published)-333.7(in)-336.4(2014)-332.7(\(1\).)-335(Table)-331.7(1)]TJ
T*
[(describes)-283.8(proposed)-280.5(criteria)-283.3(for)-285.5(genetic)-282.2(counseling.)]TJ
ET
310.847 455.301 239.074 .22678 re
f
310.847 77.386 239.074 .22675 re
f
BT
/F9 1 Tf
9.845 0 0 9.845 316.7999 470.9479 Tm
(Table)Tj
/F3 1 Tf
2.9829 0 TD
(1.)Tj
/F9 1 Tf
1.2496 0 TD
[(Situations)-317.1(in)-314.3(Which)-314.8(Genetic)-320(Counseling)]TJ
2.6777 -1.0135 TD
[(Should)-330.2(Be)-337(Proposed)]TJ
/F3 1 Tf
-7.5149 -1.5894 TD
[(I.)-332.6(Pregnant)-332.7(women)]TJ
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[(Positive)-337.5(family)-336.9(history)-335.3(for)-331.2(nonsyndromic)-336.7(CH)]TJ
1.002 -1.0077 TD
[(Dy)20.2(sh)15.5(or)21.1(mo)19.9(no)21.1(ge)19.9(ne)19.9(si)21(s)-329.1(\()0(p)21(r)0(e)19.9(v)0(i)20.9(o)0(u)21.1(s)0(l)15.3(y)-323.5(af)19.9(fe)19.9(ct)19.7(ed)-314.1(ch)19.9(il)14.9(d\))-312.9(\(1)21(/)]TJ
/F4 1 Tf
20.3104 0 TD
[(++)21.4(+)]TJ
/F3 1 Tf
1.6239 0 TD
(\))Tj
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[(Dysgenesis)-254.6(\(at)-257.7(least)-255.1(one)-251.8(member)-252.5(of)-255.4(the)-251.9(family\))-251.5(\(2/)]TJ
/F4 1 Tf
20.3507 0 TD
(++)Tj
/F3 1 Tf
1.1056 0 TD
(0\))Tj
-22.4583 -1.0135 TD
[(Positive)-337.5(family)-336.9(history)-335.3(of)-330.2(syndromic)-333.7(CH)-337.8(with:)]TJ
1.002 -1.0077 TD
[(Neurological)-339.2(disorders,)-335.8(including)-333.1(unexplained)]TJ
.9732 -1.0135 TD
[(intellectual)-340.1(impairment)]TJ
-.9732 -1.0135 TD
(Deafness)Tj
T*
[(Congenital)-336.2(heart)-335.7(disease,)-336.1(surfactant)-336.1(deciency)]TJ
.9732 -1.0077 TD
(syndrome)Tj
-.9732 -1.0135 TD
[(Cleft)-335.7(palate)]TJ
T*
[(Kidney)-336.3(malformations)]TJ
T*
[(Any)-274.4(sign)-280.4(of)-272.6(Albright)-279.9(hereditary)-278.7(osteodystrophy)-274.2(\()]TJ
/F5 1 Tf
19.7864 0 TD
(GNAS)Tj
/F3 1 Tf
-18.8132 -1.0077 TD
[(mutation\))-340(\(1/)]TJ
/F4 1 Tf
5.3554 0 TD
(++)Tj
/F3 1 Tf
1.1056 0 TD
(0\))Tj
-7.4343 -1.0135 TD
[(Unexplained)-338(abnormality)-337.4(of)-330.2(T4,)-334.8(T3,)-334.8(or)-336(TSH)-333(levels)-336.7(in)]TJ
.9732 -1.0135 TD
[(family)-336.9(members)-339.7(\(mild)-328.9(forms)-334.2(of)-336(CH\))-333(\(2/)]TJ
/F4 1 Tf
16.481 0 TD
(++)Tj
/F3 1 Tf
1.1056 0 TD
(0\))Tj
-20.558 -1.3129 TD
[(II.)-333.6(Infant)-335.5(or)-330.2(child)-334.7(with)-333.4(CH)-337.8(\(2/)]TJ
/F4 1 Tf
12.4327 0 TD
(++)Tj
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1.1056 0 TD
(0\))Tj
-12.5421 -1.0135 TD
[(Subject)-337.7(with)]TJ
1.002 -1.0135 TD
(Deafness)Tj
0 -1.0077 TD
[(Neurological)-339.2(signs)-333(\(hypotonia,)-337.3(choreoathetosis,)]TJ
.9732 -1.0135 TD
[(intellectual)-340.1(disability\))]TJ
-.9732 -1.0135 TD
[(Lung)-333.4(disorders)-338.1(\(surfactant)-337.1(deciency)-336.1(syndrome,)]TJ
.9732 -1.0135 TD
[(interstitial)-337.8(lung)-338.1(disease\))]TJ
-.9732 -1.0077 TD
[(Congenital)-336.2(heart)-335.7(disease)]TJ
0 -1.0135 TD
[(Cleft)-335.7(palate)]TJ
T*
[(Kidney)-336.3(malformations)]TJ
0 -1.0077 TD
[(Any)-274.4(sign)-280.4(of)-272.6(Albright)-279.9(hereditary)-278.7(osteodystrophy)-274.2(\()]TJ
/F5 1 Tf
19.7864 0 TD
(GNAS)Tj
/F3 1 Tf
-18.8132 -1.0135 TD
(mutation\))Tj
-1.9752 -1.0135 TD
[(Family)-336.7(history)]TJ
1.002 -1.0135 TD
(Consanguinity)Tj
0 -1.0077 TD
[(Kidney)-336.3(malformations)]TJ
0 -1.0135 TD
(Deafness)Tj
T*
[(Specic)-338.5(malformations)-334.6(\(as)-338(already)-333.1(listed\))]TJ
T*
[(Unexplained)-338(intellectual)-340.1(impairment)-331.8(despite)-337.7(adequate)]TJ
.9732 -1.0077 TD
[(treatment)-342.4(of)-330.2(CH)-337.8(in)-330.4(family)-336.9(members)]TJ
-.9732 -1.0135 TD
[(Any)-274.4(sign)-280.4(of)-272.6(Albright)-279.9(hereditary)-278.7(osteodystrophy)-274.2(\()]TJ
/F5 1 Tf
19.7864 0 TD
(GNAS)Tj
/F3 1 Tf
-18.8132 -1.0135 TD
(mutation\))Tj
8.7511 0 0 8.7511 318.7841 65.537 Tm
[(CH,)-478(congenital)-467.5(hypothyroidism;)-470.8(T3,)-475.9(triiodothyronine;)-469.8(T4,)-469.4(thy-)]TJ
-.907 -1.0236 TD
[(roxine;)-332.4(TSH,)-334.3(thyrotropin.)]TJ
/F6 1 Tf
8.9663 0 0 8.9663 59.7543 749.7069 Tm
[(GUIDELINES)-340.4(FOR)-334(CONGENITAL)-339.9(HYPOTHYROIDISM)-28059.1(403)]TJ
ET
endstream
endobj
185 0 obj
<>stream
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BT
/F3 1 Tf
9.843 0 0 9.843 72 725.1588 Tm
0 0 0 rg
0 Tc
0 Tw
[(Detailed)-261.2(phenotypic)-267(description)-262.3(of)-261.4(the)-258(index)-260.2(patients)-265.8(CH)]TJ
-1.0137 -1.1174 TD
[(form)-264.7(is)-267.1(essential)-272.6(and)-269.4(should)-265.7(include)-269.5(the)-263.8(presence)-272.4(or)-267.1(absence)]TJ
0 -1.1116 TD
[(of)-445.7(associated)-453.3(malformations)-457(\(syndromic)-451(vs.)-443.2(isolated)-454.8(CH\),)]TJ
T*
[(guiding)-399.6(genetic)-403.1(counseling)-399.3(and,)-399.6(if)-399.7(possible)-401.5(and)-401.9(necessary,)]TJ
T*
[(genetic)-351.3(testin)-8(g.)-350.1(Patients)-351(and)-350(family)-354.8(members)-352.1(should)-352.1(be)-348.9(in-)]TJ
0 -1.1174 TD
[(formed)-285.4(about)-277.5(the)-281.1(inheritance)-287.8(and)-280.9(the)-281.1(risk)-280.8(of)-278.6(recurrence,)-285.1(and)]TJ
0 -1.1116 TD
[(the)-194.7(presence)-191.8(of)-192.2(associated)-194.1(disorders)-195.1(in)-192.4(case)-192(of)-192.2(syndromic)-196.5(CH.)]TJ
1.0137 -1.1116 TD
[(Accurate)-365.8(genotyping/genetic)-365(testing)-360.4(of)-359.3(patients)-356.9(with)-362.6(CH)]TJ
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[(by)-336.3(mutation)-334.1(analysis)-333.5(of)-336.2(candidate)-337.4(genes)-335.9(can)-333.9(or)-336.2(may)-334(\(i\))-331.7(ex-)]TJ
0 -1.1116 TD
[(plain)-185.5(the)-183.1(disease;)-185(\(ii\))-183.1(predict)-183.1(the)-188.9(risk)-182.9(of)-180.7(CH)-182.7(and)-183(extrathyroidal)]TJ
T*
[(defects)-345.2(in)-336.4(family)-343.3(members)-340.6(\(to)-337.5(be)-337.4(performed)-341.7(in)-342.1(all)-338.8(cases)-342.7(of)]TJ
0 -1.1174 TD
[(syndromic)-461.5(primary)-453.7(CH,)-456.8(and)-459.5(in)-451.6(central)-460.7(CH\);)-461.4(\(iii\))-455.1(identify)]TJ
0 -1.1116 TD
[(carriers)-369.2(of)]TJ
/F5 1 Tf
4.5674 0 TD
(NKX2-1)Tj
/F3 1 Tf
3.6459 0 TD
[(gene)-363.8(mutations)-363.8(who)-367(are)-362.7(at)-360.6(risk)-367.2(of)-359.3(life-)]TJ
-8.2133 -1.1116 TD
[(threatening)-401.9(respiratory)-406.1(disease)-402.6(\(208\);)-398.3(\(iv\))-401.9(enable)-401.9()50.8(person-)]TJ
T*
[(alized)46.2()-421.5(LT4)-420.4(treatment)-423.9(to)-422.8(prevent)-424.8(goiter)-422.7(formation,)-424.9(which)]TJ
0 -1.1174 TD
[(may)-299.4(occur)-301.5(in)-301.8(CH)-297.8(due)-304(to)]TJ
/F5 1 Tf
10.1486 0 TD
(TPO)Tj
/F3 1 Tf
2.1887 0 TD
(or)Tj
/F5 1 Tf
1.1289 0 TD
(TG)Tj
/F3 1 Tf
1.5724 0 TD
[(gene)-300.5(mutations)-306.2(if)-296(TSH)]TJ
-15.0386 -1.1116 TD
[(concentrations)-279.4(are)-270.5(not)-268.4(carefully)-278.5(kept)-270.6(in)-273(the)-269.5(lower)-272.6(part)-270.6(of)-272.9(the)]TJ
T*
[(reference)-361.2(interval;)-352.5(and)-355.8(\(v\))-354.6(identify)-355.9(patients)-351.2(with)-356.9(mild)-351.5(TSH)]TJ
0 -1.1174 TD
[(resistance)-389.9(in)-376.7(whom)-386.6(long-term)-381.1(LT4)-385.8(treatment)-383.6(may)-380.1(be)-383.5(non-)]TJ
0 -1.1116 TD
[(benecial)-285.4(\(50\).)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 62.022 490.2235 Tm
[(5.2.)-502.8(Genetics)-335.5(of)-330.2(CH)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 446.6833 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 445.3794 Tm
[(If)-393.8(genetic)-403.1(testing)-395(is)-399.6(performed,)-396.9(its)-395(aim)-397.5(should)-398.2(be)-395(im-)]TJ
0 -1.1116 TD
[(proving)-330.4(diagnosis,)-336.9(treatment,)-341(or)-330.5(prognosis)-337.9(\(1/)]TJ
/F4 1 Tf
18.7018 0 TD
(++)Tj
/F3 1 Tf
1.1001 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 424.7999 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 423.4959 Tm
[(Before)-568.6(doing)-564.3(so,)-564.1(possibilities)-568.6(and)-568.9(limits)-566.9(of)-566.6(genetic)]TJ
0 -1.1116 TD
[(testing)-498.6(should)-501.9(be)-504.5(discussed)-501.4(with)-500.9(parents)-505.3(or)-497.5(families)]TJ
0 -1.1174 TD
(\(1/)Tj
/F4 1 Tf
1.1116 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 391.918 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 390.6141 Tm
[(When)-244(available,)-254.5(genetic)-247.6(testing)-245.2(should)-248.5(be)-245.3(performed)-249.5(by)]TJ
0 -1.1116 TD
[(means)-319.9(of)-318.9(new)-316.4(techn)-8(iques,)-315.3(such)-322.2(as)-320(CGH)-317.1(array,)-322.2(NGS)-321.7(of)]TJ
0 -1.1174 TD
[(gene)-335(panels)-337.2(\(targeted)-336.1(NGS\),)-337.7(or)-330.5(WES)-334.9(\(1/)]TJ
/F4 1 Tf
16.6686 0 TD
(++)Tj
/F3 1 Tf
1.1001 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 359.0361 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 357.7322 Tm
[(Pr)21(ef)19.7(er)19.7(ab)13.9(ly)20.7(,)-274.1(g)0(e)19.7(n)0(e)19.7(t)0(i)20.6(c)-278.7(te)19.6(st)20.9(in)15(g)-271.8(o)0(r)-267.1(s)0(t)20.9(u)0(d)15.1(i)0(e)19.6(s)-271.6(sh)15.3(ou)20.8(ld)-267.3(be)-262.5(pr)15.1(ec)18.5(ed)19.7(ed)]TJ
0 -1.1116 TD
[(by)-405.4(ca)18.5(re)19.7(fu)20.9(l)-415.9(p)0(h)20.8(e)0(n)19.7(o)0(t)20.7(y)0(p)20.8(i)0(c)-406.7(d)0(e)19.7(s)0(c)14.1(r)0(i)20.7(p)0(t)20.7(i)0(o)20.7(n)-415.8(of)-405.3(th)20.7(e)-417(p)0(a)19.7(t)0(i)20.6(e)0(n)19.7(t)0()20.7(s)-415.6(CH)18.9(,)]TJ
0 -1.1174 TD
[(in)20.7(cl)19.5(ud)20.8(in)20.7(g)-323.6(m)0(o)19.6(r)0(p)15.1(h)0(o)20.8(l)0(o)20.7(g)0(y)-313.2(o)0(f)-313.2(t)0(h)20.7(e)-324.8(th)20.7(yr)15.1(oi)20.7(d)-323.6(g)0(l)20.7(a)0(n)19.7(d)-323.6(\(2)20.9(/)]TJ
/F4 1 Tf
18.5981 0 TD
(++)Tj
/F3 1 Tf
1.0886 0 TD
[(0\))20.9(.)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 72 326.1542 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 324.8503 Tm
[(Not)-326.8(only)-327.1(thyroid)-330.5(dyshormonogenesis,)-336.3(but)-326(also)-328(familial)]TJ
0 -1.1116 TD
[(occurrence)-460.3(of)-451.4(dysgenesis)-456.4(and)-459.5(central)-454.9(hypothyroidism)]TJ
0 -1.1174 TD
[(should)-334.8(lead)-335.2(to)-330.6(further)-337.2(genetic)-339.8(testing)-331.6(\(1/)]TJ
/F4 1 Tf
16.5534 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 293.2723 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 291.9684 Tm
[(Any)-441.9(syndromic)-450(association)-447.6(should)-444.3(be)-446.9(studied)-446.7(geneti-)]TJ
0 -1.1116 TD
[(cally,)-322.5(not)-326(only)-321.3(to)-324.9(improve)-321.2(genetic)-328.2(counseling,)-327.9(but)-320.2(also)]TJ
T*
[(to)-342.1(identify)-350.2(new)-345.2(candidate)-348.9(genes)-347.5(explaining)-347.8(the)-350.2(associ-)]TJ
0 -1.1174 TD
[(ation)-335.2(\(1/)]TJ
/F4 1 Tf
3.4558 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 72 249.4488 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 80.9008 248.1448 Tm
[(Further)-388.9(research)-387.6(is)-388(needed)-390.2(to)-388.2(better)-389.3(dene)-387.8(patients)-391.5(or)]TJ
0 -1.1116 TD
[(patient)-436.6(groups)-438.4(that)-437.8(will)-437.6(benet)-435.1(most)-437.5(from)-437.5(these)-439.7(new)]TJ
0 -1.1174 TD
[(diagnostic)-336.1(possibilities)-338.2(\(2/)]TJ
/F4 1 Tf
10.6958 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F12 1 Tf
8.9663 0 0 8.9663 72 194.0598 Tm
(Evidence)Tj
/F5 1 Tf
9.843 0 0 9.843 72 177.1086 Tm
[(Primary)-448.4(CH.)]TJ
/F3 1 Tf
5.8634 0 TD
[(TD)-395.9(due)-390.4(to)-394(thyroid)-399.6(maldevelopment)-397.3(is)-393.8(the)]TJ
-6.8771 -1.1116 TD
[(most)-380(frequent)-379.8(cause)-383.2(of)-376.5(permanent)-383.4(primary)-378.8(CH,)-376.2(explaining)]TJ
/F10 1 Tf
-.2016 -1.1116 TD
(*)Tj
/F3 1 Tf
1.0022 0 TD
[(65%)-326.9(of)-330.5(cases)-331.1(\(12,209\).)-331.3(In)-330.5(contrast)-328(to)-330.6(TD)-332.6(with)-328.1(conditions)]TJ
-.8006 -1.1174 TD
[(such)-351(as)-354.5(athyreosis)-353(or)-347.7(thyroid)-353.5(ectopy,)-352.3(the)-350.2(other)-352.3(35%)-350(is)-347.7(best)]TJ
0 -1.1116 TD
[(described)-203.4(as)-204.8(GIS)-199.8(of)-198(which)]TJ
/F4 1 Tf
10.5633 0 TD
(<)Tj
/F3 1 Tf
.5529 0 TD
[(50%)-200.2(is)-198(due)-200.3(to)-198.2(inherited)-208.4(defects)-201.2(of)]TJ
-11.1162 -1.1116 TD
[(TH)-609(synthesis)-609.8(\(dyshormonogenesis\).)-609.1(TD)-609(is)-601.1(considered)-613.4(a)]TJ
0 -1.1174 TD
[(sporadic)-201.1(disease.)-204.4(However,)-199.5(the)-200.4(familial)-197.2(component)-203.7(cannot)-199.1(be)]TJ
0 -1.1116 TD
[(ignored,)-317.7(suggesting)-317.3(a)-319(genetic)-316.7(predisposition)-316.2(and)-321.2(a)-313.3(probably)]TJ
T*
-.0158 Tc
[(com)-15.8(p)9.6(lex)-247.3(i).3(n)-15.8(h)10.8(eri)-15.8(t)10.5(ance)-248.4(m)-15.8(o)9.6(de)-248.4(\(21)-15.8(0)10.8(,)-2(211\))-15.8(.)-233.4(I)-15.8(n)-236.8(only)-247.3(5)-15.8(%)-237.9(o).4(f)-247.2(T)-.8(D)-248.2(cas)-15.8(e)9.8(s).6(,)]TJ
0 -1.1174 TD
-.0156 Tc
[(a)-288.6(g).6(enet)-15.6(i)10.7(c)-282.8(ca)-15.6(u)9.8(s).8(e)-288.6(i).5(s)-287.2(i).5(dent)-15.6(i)10.7().7(ed)-287.4(wit)-15.6(h)-271.4(mut)-15.6(a)9.7(tion)-15.6(s)-271(i)-15.6(n)]TJ
/F5 1 Tf
18.2525 0 TD
-.0163 Tc
[(TS)-16.3(H)9.4(R)]TJ
/F3 1 Tf
2.6091 0 TD
[(\(2)-16.2(1)10.4(2\),)-284.6(o)-16.2(r)]TJ
-20.8617 -1.1116 TD
0 Tc
[(i)16.1(n)-461.9(g)16.2(e)15(ne)25.4(s)-461.7(e)15(n)16.2(c)15(o)16.2(d)0(i)26.5(n)16.2(g)-461.9(t)16.1(r)16.2(a)15(ns)26.8(c)15(r)16.2(ip)26.5(t)16.1(i)16.1(o)0(n)-445.7(f)16.2(ac)24.3(t)16.1(o)16.2(rs)-445.5(i)16.1(n)0(v)26.6(o)16.2(l)16.1(v)0(e)25.4(d)-456.1(in)-445.8(th)26.5(y)16.2(r)16.2(o)0(i)26.5(d)]TJ
T*
[(d)16.2(e)15(ve)25.4(l)16.1(o)16.2(pm)25.4(e)15(n)16.2(t)-496.6(\()]TJ
/F5 1 Tf
5.8576 0 TD
-.0154 Tc
[(TTF1/)-15.4(N)10(K)-.2(X2.1)]TJ
/F3 1 Tf
5.5293 0 TD
0 Tc
(,)Tj
/F5 1 Tf
.7488 0 TD
-.015 Tc
[(PAX)-15(8)]TJ
/F3 1 Tf
2.2866 0 TD
0 Tc
(,)Tj
/F5 1 Tf
.7488 0 TD
-.0151 Tc
(FOXE1)Tj
/F3 1 Tf
2.9835 0 TD
0 Tc
(,)Tj
/F5 1 Tf
.7488 0 TD
-.0158 Tc
[(NK)-15.8(X)8.6(2-5)]TJ
/F3 1 Tf
3.1909 0 TD
0 Tc
[(,)-498.8(and)]TJ
/F5 1 Tf
3.4097 67.9242 TD
(GLIS3)Tj
/F3 1 Tf
2.6091 0 TD
[(\))-404.2(\(213,214\).)-407.3(During)-405(the)-402(past)-408.7(years,)-408.5(novel)-404.2(and)-407.6(faster)]TJ
-2.6091 -1.1174 TD
[(genet)-8(ic)-193.6(and)-200.3(molecular)-199.2(tests,)-200(and)-194.5(the)-200.4(availability)-201.8(of)-198(large)-198(well-)]TJ
0 -1.1116 TD
[(phenotyped)-318.7(cohorts)-319.8(of)-319(patients)-316.6(have)-317.8(led)-315.6(to)-319.1(the)-315.6(discovery)-317.4(of)]TJ
T*
[(new)-391.2(genetic)-391.6(causes)-389.9(of)-388.1(CH.)-393.4(Heterozygous)-391.9(mutations)-392.7(in)-388.2(the)]TJ
/F5 1 Tf
T*
(JAG1)Tj
/F3 1 Tf
2.5458 0 TD
[(gene,)-257.8(respon)-7.5(sible)-260.2(for)-262.4(Alagille)-260.2(syndrome)-264.4(and)-257.9(encod)-7.8(ing)]TJ
-2.5458 -1.1174 TD
[(the)-211.9(jagged)-204.9(protein)-210.7(in)-203.9(the)-206.2(Notch)-209.3(pathway,)-210.3(have)-208.3(been)-208.3(identied)]TJ
0 -1.1116 TD
[(in)-353.7(TD)-349.8(patients)-351.2(\(mainly)-350.1(with)-351.1(orthotopic)-352.4(thyroid)-353.5(hypoplasia\))]TJ
T*
[(\(77,215\).)-342.8(By)-343.1(WES)-340.7(in)-342.1(familial)-341.2(TD)-344.1(cases,)-346.1(Carre)]TJ
18.7939 .0403 TD
()Tj
/F5 1 Tf
.7257 -.0403 TD
[(et)-343.3(al.)]TJ
/F3 1 Tf
2.4421 0 TD
(found)Tj
-21.9618 -1.1174 TD
[(borealin)-426.1(\(encoded)-421.2(by)]TJ
/F5 1 Tf
9.227 0 TD
(BOREALIN)Tj
/F3 1 Tf
4.7287 0 TD
[(\),)-419.2(a)-417(major)-422.7(component)-416.8(of)]TJ
-13.9558 -1.1116 TD
[(chromosomal)-512.2(passenger)-508.3(complex,)-510.2(to)-503.4(be)-510.2(also)-506.6(involved)-505.6(in)]TJ
T*
[(thyrocyte)-369.6(migration)-364(and)-361.6(adhesion,)-360.1(explaining)-365.1(cases)-365.7(of)-365(thy-)]TJ
0 -1.1174 TD
[(roid)-367.4(ectopy)-366.2(\(216\).)-366(Mutations)-369.3(or)-365(deletion)-368.6(in)-359.4(the)]TJ
/F5 1 Tf
19.7731 0 TD
-.0158 Tc
[(NTN)5.1(1)]TJ
/F3 1 Tf
2.6783 0 TD
-.0156 Tc
[(gen)6.3(e)]TJ
-22.4513 -1.1116 TD
-.0168 Tc
[(have)-255.2(been)-254(foun)5.1(d)-259.8(i)5(n)-259.8(p)-.6(atients)-253.8(w)-1.5(it)5(h)-259.8(T)-1.8(D.)-256.4(Net)5(r)-.6(in)-254(is)-259.6(p)5.1(a)-1.8(rt)-254.2(of)-254(a)-261(f)-.6(ami)5(l)-.7(y)]TJ
T*
-.0166 Tc
[(of)-518.8(lamini)5.2(n-relat)5.2(e)-1.6(d)-518.8(p)-.4(r)5.4(o)-.4(tei)5.2(n)-.4(s,)-515.4(invo)5.3(lved)-518.8(in)-518.8(cell)-518.9(mi)5.2(grat)5.2(i)-.5(on)-518.8(and)]TJ
T*
[(poss)5.6(i)-.4(bly)-368.9(i)5.3(n)-368.9(t)-.4(he)-370.1(devel)5.3(opment)-369.1(o)5.4(f)-374.7(p)5.4(har)5.5(yng)5.4(eal)-369.1(vessels)-368.7(\(217)5.4(\).)-371.3(F)5.6(i)-.5(-)]TJ
0 -1.1174 TD
-.0164 Tc
[(nall)5.4(y,)-313.6(mut)5.4(a)-1.4(tio)5.5(ns)-311(in)-311.2(t)5.4(h)-.2(e)]TJ
/F5 1 Tf
9.1234 0 TD
-.0155 Tc
[(TU)5.6(BB1)]TJ
/F3 1 Tf
3.2254 0 TD
-.0166 Tc
[(\()5.4(t)-.5(ub)5.3(ulin)5.3(,)-313.8(b)-.4(eta)-312.6(1)-311.4(class)-311.2(V)4.5(I\))-311.4(gen)5.3(e)]TJ
-12.3488 -1.1116 TD
[(have)-404.7(recent)5.3(ly)-409.3(been)-409.3(id)5.4(ent)5.3(i)-.4(ed)-403.5(i)-.4(n)-409.3(p)-.3(atients)-409.1(f)-.3(r)5.5(o)-.3(m)-410.5(t)5.3(hree)-404.7(f)-.3(amili)5.3(e)-1.5(s)]TJ
T*
-.0164 Tc
[(with)-466.8(TD)-473.4(\()5.6(m)-1.4(os)5.7(tly)-472.5(e)4.4(cto)5.5(py\))-472.5(and)-472.5(a)4.4(bno)5.5(rmal)-472.6(platel)5.4(et)-472.6(p)5.5(hysi)5.4(o)-.2(lo)5.6(gy)]TJ
0 -1.1174 TD
[(\(bas)5.7(a)-1.4(l)-357.4(a)-1.4(ctiv)5.5(atio)5.5(n)-357.3(a)-1.4(nd)-357.3(exag)5.5(ger)5.6(a)-1.4(ted)-357.3(p)-.2(lat)5.4(e)-1.4(let)-357.5(a)-1.4(gg)5.5(reg)5.5(a)-1.4(tio)5.5(n\))-357.3(\(2)5.5(18\).)]TJ
0 -1.1116 TD
-.0166 Tc
[(Functio)5.3(nal)-196.4(s)5.5(tudi)5.2(es)-196.1(in)-196.2(k)5.3(nockou)5.3(t)-196.4(m)-1.6(ice)-197.4(v)-.4(alidated)-196.2(t)5.2(h)-.4(e)-197.4(r)-.4(o)5.3(l)-.5(e)-197.4(o)-.4(f)-196.2(T)4.1(ubb)5.3(1)]TJ
T*
[(in)-282.5(t)5.3(hyr)5.5(oid)-276.8(d)-.3(evelo)5.4(p)-.3(ment,)-273.4(functio)5.4(n,)-279.1(an)5.4(d)-282.5(d)5.4(isease.)]TJ
1.0137 -1.1174 TD
0 Tc
[(With)-473.5(respect)-471.9(to)-468.9(the)-471.1(cause)-475.3(of)-468.7(the)-471.1(mild)-472.4(nonautoimmune)]TJ
-1.0137 -1.1116 TD
[(subcli)-7.8(nical)-555.3(hypothyroidism)-558.2(in)-561(neonates)-559.4(and)-557.4(infants)-561.8(with)]TJ
T*
[(Downs)-255.8(syndrome,)-250.6(new)-253(insights)-250.7(were)-255.2(provided)-252(by)-249.9(a)-249.9(study)-247.3(in)]TJ
0 -1.1174 TD
[(Dyrk1A)-440.3(\()]TJ
/F4 1 Tf
4.0433 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(/)Tj
/F4 1 Tf
.2822 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
[(\))-433(mice,)-443.5(showing)-434.7(abnormal)-444.4(thyroid)-434.2(develop-)]TJ
-5.9843 -1.1116 TD
[(ment)-427.4(and)-424.9(function)-430.7(\(42\).)-422.5(How)-425.5(overexpression)-427.5(of)-428.4(this)-424.9(gene)]TJ
T*
[(causes)-361.1(thyroid)-353.5(abnormalities)-353.4(remains)-356.8(to)-353.7(be)-354.7(elucidated.)-353.6(An-)]TJ
T*
[(other)-219.9(more)-214.1(frequent)-212.8(form)-212.9(of)-215.3(syndromic)-213.8(CH)-217.2(is)-209.5(BLT)-214.1(syndrome)]TJ
0 -1.1174 TD
[(due)-292.5(to)]TJ
/F5 1 Tf
2.8165 0 TD
(NKX2-1)Tj
/F3 1 Tf
3.571 0 TD
[(haploinsufciency.)-297.5(Extensive)-295.7(genetic)-293.7(analy-)]TJ
-6.3875 -1.1116 TD
[(sis)-291(of)-290.1(a)-290.2(large)-290.1(group)-287.7(of)-290.2(affected)-290(patients)-293.6(revealed)-295.8(novel)-289(vari-)]TJ
T*
[(ants,)-435.2(expanding)-432.8(BLT)-432.9(syndrome)-437.2(phenotype)-432.8(\(219\).)-429.3(Table)-435.4(2)]TJ
0 -1.1174 TD
[(summarizes)-287.4(genes)-284.1(associated)-286.2(with)-282(TD.)]TJ
1.0137 -1.1116 TD
[(In)-261.3(contrast)-264.6(to)-261.5(TD,)-261.1(thyroid)-255.6(dyshormonog)-7.4(enesis)-262.1(is)-261.3(inherited)]TJ
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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[(VAN)-332.3(TROTSENBURG)-337.1(ET)-338.7(AL.)]TJ
ET
endstream
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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26.5234 27.8367 TD
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T*
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[(TRH)-484.5(resistance)-493.6(does)-489.2(not)-487.3(cause)-486.9(severe)-493.7(neonatal)-490.6(hypothy-)]TJ
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[(roidism.)-409.8(The)-408.8(diagnosis)-408.4(in)-405.5(three)-411.1(of)-405.3(the)-407.8(four)-413.3(probands)-407.2(with)]TJ
T*
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3.6689 0 TD
(TRHR)Tj
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2.9202 0 TD
[(mutations)-427.2(was)-419.8(made)-422.7(during)-421.4(childhood)-426(be-)]TJ
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[(cause)-388.9(of)-393.8(delayed)-391.5(growth)-387.7(accompanied)-393.7(by)-393.9(lethargy)-391.5(and)-390.4(fa-)]TJ
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[(tigue)-300.7(or)-307.4(by)-301.7(overweight.)-305.9(However,)-308.9(complete)-307.5(TRH)-305.9(resistance)]TJ
T*
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(IGSF1)Tj
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[(\))-208.4(mutations)-208.3(are)-212.9(the)-211.9(molecular)-210.7(cause)-210.4(of)-209.5(a)-209.6(recently)]TJ
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[(described)-468.3(X-linked)-466.1(syndrome,)-469.4(including)-466.5(mild-to-moderate)]TJ
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[(abnormal)-231.3(testicular)-233.7(growth)-232.2(leading)-229.2(to)-227(adult)-231.6(macro-orchidism)]TJ
T*
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[(central)-460.7(CH.)-462.6(Recent)-466.3(data)-461.9(indicate)-467.7(IGSF1)-461(as)-458.2(the)-465.4(most)-460.6(fre-)]TJ
T*
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T*
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T*
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(2.)Tj
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(phenotype)Tj
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[(Mode)-334.4(of)]TJ
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[(inheritance)-3222.3(Associated)-335.9(conditions)]TJ
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(NKX2-1)Tj
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T*
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(FOXE1)Tj
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[(\(602617\))-1303.6(NF)-10581.1(Athyreosis,)-337.7(severe)]TJ
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(hypoplasia)Tj
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[(\(horseshoe)-334.4(kidney,)-338.9(renal)]TJ
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[(agenesis,)-337.1(ureter,)-334.3(and)-338.1(testes)]TJ
0 -1.0135 TD
[(anomalies\),)-340.6(variable)]TJ
T*
(expressivity)Tj
/F5 1 Tf
-37.8279 -1.0135 TD
(NKX25)Tj
/F3 1 Tf
3.7834 0 TD
[(\(600584\))-917.8(NF)-10581.1(Thyroid)]TJ
/F5 1 Tf
19.9188 0 TD
[(in)-255.5(situ)]TJ
/F3 1 Tf
2.4877 0 TD
[(,)-251(variable)]TJ
-4.9811 -1.0077 TD
(hypothyroidism)Tj
9.6456 1.0077 TD
[(Unclear)-2810.1(Congenital)-336.2(heart)-335.7(malformations)]TJ
/F5 1 Tf
-30.8543 -2.0213 TD
(GLIS3)Tj
/F3 1 Tf
2.9369 0 TD
[(\(610192\))-1764.3(NF)-10581.1(Variable)-7182(AR)-4599.1(Neonatal)-335.1(diabetes,)-337.5(polycystic)]TJ
34.891 -1.0135 TD
[(kidneys,)-334(and)-338.1(cholestasis)]TJ
/F5 1 Tf
-37.8279 -1.0135 TD
(JAG1)Tj
/F3 1 Tf
2.6144 0 TD
[(\(601920\))-2086.7(Jagged)-336.3(1:)-336.2(Notch)-335.4(receptor)]TJ
6.749 -1.0077 TD
(ligand)Tj
10.8549 1.0077 TD
[(Variable)-335.1(orthotopic)]TJ
.9905 -1.0077 TD
(hypoplasia)Tj
9.6456 1.0077 TD
[(AD)-4547.1(Heart)-336.5(malformations,)-338(variable)]TJ
6.9736 -1.0077 TD
(expressivity)Tj
/F5 1 Tf
-37.8279 -1.0135 TD
(TBX1)Tj
/F3 1 Tf
2.6144 0 TD
[(\(602054\))-2086.7(NF)-10581.1(Thyroid)]TJ
/F5 1 Tf
21.1684 0 TD
[(in)-330.4(situ)]TJ
/F3 1 Tf
7.0715 0 TD
[(AD)-4547.1(Di)-331.2(George)-337.3(syndrome)-338.3(with)]TJ
6.9736 -1.0135 TD
[(congenital)-336.4(heart)]TJ
0 -1.0077 TD
[(malformations,)-338(variable)]TJ
0 -1.0135 TD
(expressivity)Tj
/F5 1 Tf
-37.8279 -1.0135 TD
(NTN1)Tj
/F3 1 Tf
2.718 0 TD
[(\(601614\))-1983.1(Laminin-related)-339.3(secreted)]TJ
6.6454 -1.0135 TD
(protein)Tj
10.8549 1.0135 TD
[(Thyroid)-336.5(ectopy)-4396.5(unknown)-2265.1(Arthrogryposis)]TJ
/F5 1 Tf
-20.2183 -2.0213 TD
(CDCA8)Tj
/F3 1 Tf
3.5012 0 TD
[(\(609977\))-1199.9(Cell)-340.5(division)-330.7(cycle)]TJ
5.8622 -1.0135 TD
[(associated)-337.1(protein)-336.7(8)-329.2(o)0(r)]TJ
T*
[(Borealin:)-335.2(component)-335.1(of)]TJ
T*
[(the)-332.6(chromosomal)]TJ
0 -1.0077 TD
[(passenger)-334.6(complex)]TJ
10.8549 4.0483 TD
[(Thyroid)-336.5(ectopy,)]TJ
.9905 -1.0135 TD
(hemiagenesis,)Tj
T*
[(thyroid)-335.5(asymmetry)]TJ
9.6456 2.027 TD
(Variable)Tj
.9905 -1.0135 TD
[(\(AD,)-336.2(AR\))]TJ
4.9927 1.0135 TD
[(None)-334.2(in)-336.2(sporadic)-332.7(cases)]TJ
/F5 1 Tf
-36.8374 -5.0618 TD
(TUBB1)Tj
/F3 1 Tf
3.3342 0 TD
[(\(612901\))-1366.9(Member)-338.5(of)-336(the)]TJ
/F14 1 Tf
11.4941 0 TD
(b)Tj
/F3 1 Tf
.5528 0 TD
(-tubulin)Tj
-6.0177 -1.0135 TD
[(protein)-330.9(family)]TJ
10.8549 1.0135 TD
[(Thyroid)-336.5(dysgenesis)-2741.4(AD)-4547.1(Formation)-333.9(of)-336(macroplatelets)]TJ
17.6096 -1.0135 TD
[(and)-332.4(hyperaggregation)-337.6(of)]TJ
0 -1.0077 TD
(platelets)Tj
8.7511 0 0 8.7511 67.748 371.3385 Tm
[(AD,)-264(autosomal)-263.9(dominant;)-256.6(AR,)-264.2(autosomal)-263.9(recessive;)-264.4(NF,)-261.6(nuclear)-264.8(factor;)-267.4(OMIM,)-258.9(Online)-266(Mendelian)-259.8(Inheritance)-265.1(in)-262(Men)-260.5(\(https://www.ncbi)]TJ
-.9134 -1.0236 TD
(.nlm.nih.gov/omim/\).)Tj
/F6 1 Tf
8.9663 0 0 8.9663 59.7543 749.7069 Tm
[(GUIDELINES)-340.4(FOR)-334(CONGENITAL)-339.9(HYPOTHYROIDISM)-28059.1(405)]TJ
ET
endstream
endobj
195 0 obj
<>stream
/GS1 gs
BT
/F3 1 Tf
9.843 0 0 9.843 62.022 155.2818 Tm
0 0 0 rg
0 Tc
0 Tw
[(he)19.7(ar)19.7(in)15(g)-461.9(l)0(o)20.7(s)0(s)-451.1(\()0(2)20.9(3)0(6)15.1(\))0(.)-448(F)0(i)15.1(n)0(a)19.7(l)0(l)20.6(y)0(,)-453.8(m)0(u)19.6(t)0(a)19.6(t)0(i)20.6(o)0(n)20.8(s)-467.4(in)]TJ
/F5 1 Tf
17.2906 0 TD
[(IR)19.7(S4)]TJ
/F3 1 Tf
2.3788 0 TD
-.0181 Tc
[(a)-18.1(r)1.6(e)-481.1(a)-18.1(no)-18.1(th)-18.1(er)]TJ
-19.6694 -1.1174 TD
0 Tc
[(ca)18.5(us)21(e)-261.4(o)0(f)-249.8(X)0(-)14.2(l)0(i)20.6(n)0(k)20.8(e)0(d)-251(m)0(i)19.5(l)0(d)-250(c)0(e)18.5(n)0(t)20.7(r)0(a)19.7(l)-260.4(CH)18.9(.)-262.6(S)0(i)20.9(n)0(c)19.7(e)-261.4(IR)19.8(S4)-249.7(is)-249.8(in)20.7(vo)15.1(lv)20.7(ed)-251(in)]TJ
0 -1.1116 TD
[(le)19.5(pt)20.7(in)-238.5(si)20.9(gn)20.8(al)19.5(in)20.7(g,)-234.9(th)20.7(e)-244.2(c)0(a)18.5(u)0(s)21(e)-244.2(of)-232.6(th)15(e)-244.2(c)0(e)18.5(n)0(t)20.7(r)0(a)19.7(l)-243.1(CH)-234.5(ma)18.4(y)-243(b)0(e)-233.7(d)0(i)20.7(s)0(r)21.1(u)0(p)15.1(t)0(e)19.6(d)]TJ
T*
[(le)19.5(pt)20.7(in)-296.1(si)20.9(gn)20.8(al)13.8(in)20.7(g)-300.6(\()0(2)15.1(3)0(7)20.8(\))0(.)-292.5(C)0(e)18.6(n)0(t)20.7(r)0(a)19.7(l)-306.5(CH)-292.1(is)-295.9(mo)19.6(re)-297.1(fr)20.9(eq)19.7(ue)19.7(nt)20.7(ly)-296.1(pa)19.7(rt)-296(of)]TJ
0 -1.1174 TD
[(MP)20.1(HD)-222.8(an)19.7(d)-225.7(c)0(a)18.5(n)-231.5(be)-216.5(as)14.1(so)21(ci)19.5(at)19.5(ed)-222.2(wi)19.8(th)-215.4(on)15.1(e)-226.9(o)0(r)-221(m)0(o)19.6(r)0(e)-216.4(o)0(t)20.7(h)0(e)13.9(r)-225.7(pi)20.7(tu)20.7(it)14.8(ar)19.7(y)]TJ
0 -1.1116 TD
[(ho)20.8(rm)19.6(on)15.1(e)-319(d)0(e)19.7()0(c)14.1(i)0(e)19.6(n)0(c)19.7(e)0(s)19.9(.)-326(In)-313.2(ad)19.7(di)20.7(ti)20.6(on)20.8(,)-326(a)-324.8(ce)18.5(rt)20.7(ai)19.5(n)-323.6(p)0(e)19.7(r)0(c)19.7(e)0(n)19.7(t)0(a)13.8(g)0(e)-308.6(o)0(f)-318.9(a)0(f)19.7(-)]TJ
T*
[(fe)19.7(ct)19.5(ed)-320.1(pa)19.7(ti)20.6(en)19.7(ts)-313.2(ha)19.7(s)-329.2(m)0(o)19.6(r)0(p)20.9(h)0(o)20.8(l)0(o)20.7(g)0(i)20.7(c)0(a)12.8(l)-323.8(ab)19.7(no)20.8(rm)19.6(al)19.5(it)20.6(ie)13.8(s)-323.4(o)0(f)-313.2(t)0(h)20.7(e)-324.8(pi)20.7(tu)15(i-)]TJ
0 -1.1174 TD
[(ta)19.5(ry)-486(gl)20.7(an)19.7(d)-490.7(o)0(r)-486(h)0(y)20.8(p)0(o)20.8(t)0(h)20.7(a)0(l)13.8(a)0(m)18.5(u)0(s)21(,)-493(or)-480.2(ot)20.7(he)13.9(r)-490.6(n)0(e)19.7(u)0(r)20.9(o)0(l)20.7(o)0(g)15.1(i)0(c)19.6(a)0(l)-481.5(d)0(e)19.7(f)0(e)14(c)0(t)19.5(s)]TJ
0 -1.1116 TD
[(\(2)20.9(5,)18.5(45)20.8(\).)-378.9(Ta)18.5(bl)20.7(e)-388.2(4)-381.2(pr)15.1(es)19.9(en)19.7(ts)-376.5(ge)19.7(ne)19.7(s)-386.8(i)0(m)19.5(p)0(l)20.7(i)0(c)19.6(a)0(t)13.8(e)0(d)-372(i)0(n)-376.7(c)0(e)18.5(n)0(t)20.7(r)0(a)14(l)-381.4(hy)15.1(po)20.8(-)]TJ
T*
[(th)20.7(yr)15.1(oi)20.7(di)20.7(sm)19.8(.)]TJ
/F11 1 Tf
8.9663 0 0 8.9663 313.0582 155.9055 Tm
[(5.3.)-502.8(Antenatal)-338.6(diagnostics,)-331.2(evaluation)-334.7(of)-336.6(fetal)]TJ
0 -1.2266 TD
[(thyroid)-337.5(function,)-335.5(and)-338.2(management)]TJ
0 -1.2203 TD
[(of)-336.6(fetal)-332.8(hypothyroidism)]TJ
/F12 1 Tf
1.1128 -1.8336 TD
(Summary)Tj
/F13 1 Tf
7.9702 0 0 7.9702 323.0361 101.8204 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 331.9369 100.5165 Tm
[(We)-397.3(recommend)-396(antenatal)-395.1(diagnosis)-396.9(in)-394(cases)-394.5(of)-393.8(goiter)]TJ
0 -1.1174 TD
[(fortuitously)-572.2(discovered)-567.3(during)-571.2(systematic)-574.4(ultrasound)]TJ
0 -1.1116 TD
[(examination)-489.5(of)-491.7(the)-488.4(fetus,)-488.1(in)-486.1(relation)-489.5(to)-486.1(thyroid)-491.8(dys-)]TJ
T*
[(hormonogenesis)-404.6(\(1/)]TJ
/F4 1 Tf
8.0751 0 TD
(+++)Tj
/F3 1 Tf
1.6588 0 TD
[(\);)-394(a)-399.7(familial)-404.5(recurrence)-402.6(of)-393.8(CH)]TJ
-9.7339 -1.1174 TD
[(due)-471(to)-474.6(dyshormonogenesis)-476.8(\(25%)-472(recurrence)-477.5(rate\))-474.4(\(1/)]TJ
ET
62.022 719.49 490.167 .22668 re
f
62.022 203.811 490.167 .22675 re
f
62.022 690.803 490.167 .28345 re
f
BT
/F9 1 Tf
9.845 0 0 9.845 169.285 725.1588 Tm
(Table)Tj
/F3 1 Tf
3.0002 0 TD
(3.)Tj
/F9 1 Tf
1.2496 0 TD
[(Genes)-335(Associated)-332.5(with)-334.7(Thyroid)-337.2(Dyshormonogenesis)]TJ
/F5 1 Tf
-15.145 -2.8562 TD
[(Gene)-335.4(\(OMIM\))-4753.8(Protein)-337.7(role)-3368.1(Typical)-337.7(thyroid)-330.8(phenotype)]TJ
32.8986 1.0135 TD
[(Mode)-334.4(of)]TJ
-.5874 -1.0135 TD
[(inheritance)-3015(Associated)-335.9(conditions)]TJ
-32.3112 -1.8946 TD
(TSHR)Tj
/F3 1 Tf
2.718 0 TD
[(\(603372\))-2178.9(G-protein)-333.7(coupled)]TJ
6.8354 -1.0135 TD
(receptor)Tj
8.6321 1.0135 TD
[(Complete)-341(or)-330.2(partial)-338(TSH)]TJ
.9962 -1.0135 TD
[(resistance:)-338.2(apparent)]TJ
T*
(athyreosis)Tj
/F15 1 Tf
4.3938 0 TD
(/)Tj
/F3 1 Tf
1.526 0 TD
(thyroid)Tj
/F5 1 Tf
3.2305 0 TD
(in)Tj
-9.1503 -1.0077 TD
(situ)Tj
/F3 1 Tf
1.7794 0 TD
[(and)-332.4(severe)]TJ
/F15 1 Tf
4.6759 0 TD
(/)Tj
/F3 1 Tf
1.5318 0 TD
(mild)Tj
-7.9871 -1.0135 TD
(hypothyroidism)Tj
11.7705 4.0483 TD
[(AD,)-335.2(AR)]TJ
/F5 1 Tf
-30.9522 -5.0618 TD
(GNAS)Tj
/F3 1 Tf
2.8332 0 TD
[(\(139320\))-2063.7(Alpha)-335.4(subunit)-329.6(of)-336(the)]TJ
6.7202 -1.0135 TD
[(stimulatory)-267.1(guanine)]TJ
0 -1.0077 TD
(nucleotide-binding)Tj
0 -1.0135 TD
[(protein)-336.7(\(G)-331(protein\))]TJ
8.6321 3.0348 TD
[(Partial)-337.9(TSH)-333(resistance,)-340.4(mild)]TJ
.9962 -1.0135 TD
(hypothyroidism)Tj
11.7705 1.0135 TD
(Maternal)Tj
.9905 -1.0135 TD
(inheritance,)Tj
0 -1.0077 TD
(parental)Tj
0 -1.0135 TD
[(imprinting)-334.2(of)]TJ
T*
[(gene)-334.5(locus)]TJ
6.916 4.0483 TD
(PseudoHypo)Tj
.9905 -1.0135 TD
(Parathyroidism)Tj
0 -1.0077 TD
[(\(multiple)-340.2(hormone)]TJ
0 -1.0135 TD
(resistances\))Tj
/F5 1 Tf
-39.8491 -2.027 TD
(SLC5A5)Tj
/F3 1 Tf
3.6682 0 TD
[(\(601843\))-1228.7(Sodium)-329.6(iodide)]TJ
5.8852 -1.0077 TD
(symporter)Tj
8.6321 1.0077 TD
[(Absent)-336.2(or)-336(low)-332.2(iodide)-335.7(uptake)]TJ
.9962 -1.0077 TD
[(at)-331.6(scintiscan,)-339.4(variable)]TJ
0 -1.0135 TD
[(hypothyroidism,)-335.5(and)-332.4(goiter)]TJ
11.7705 2.0213 TD
(AR)Tj
/F5 1 Tf
-30.9522 -3.0348 TD
(SLC26A4/PDS)Tj
/F3 1 Tf
.9905 -1.0135 TD
(\(605646\))Tj
7.5725 1.0135 TD
[(Pendrin:)-331.7(anion)]TJ
.9905 -1.0135 TD
(transporter)Tj
8.6321 1.0135 TD
[(Partial)-337.9(iodide)-335.7(organication)]TJ
.9962 -1.0135 TD
[(defect,)-335.5(mild-to-moderate)]TJ
0 -1.0077 TD
[(hypothyroidism,)-335.5(goiter,)]TJ
0 -1.0135 TD
[(high)-332.4(serum)-335.4(Tg)]TJ
11.7705 3.0348 TD
[(AR)-6522.5(Pendred)-337.3(syndrome:)]TJ
8.897 -1.0135 TD
[(sensorineural)-338.9(deafness)]TJ
0 -1.0077 TD
[(with)-339.1(enlarged)-334.1(vestibular)]TJ
0 -1.0135 TD
[(aqueduct,)-337.5(predisposition)]TJ
T*
[(to)-336.2(alkalosis)]TJ
/F5 1 Tf
-39.8491 -1.0077 TD
(DUOX1/DUOX2)Tj
/F3 1 Tf
.9905 -1.0135 TD
(\(606758/606759\))Tj
7.5725 1.0135 TD
[(Dual)-334.4(oxydases:)]TJ
.9905 -1.0135 TD
[(peroxide)-263.8(generating)]TJ
T*
(system)Tj
8.6321 2.027 TD
[(Pa)14.3(rt)20.9(ia)19.7(l)-323.6(o)0(r)-312.9(c)0(o)19.9(m)0(p)19.9(l)0(e)19.7(t)0(e)-314.3(i)0(o)15.1(d)0(i)20.9(d)0(e)]TJ
.9962 -1.0135 TD
[(or)21.1(ga)19.9(ni)20.9(c)20.1(at)13.9(io)20.9(n)-254.4(d)0(e)14.1(f)0(e)19.9(c)0(t)19.7(,)-256.8(go)21.1(it)14.9(er)19.9(,)]TJ
T*
[(tr)20.9(an)19.9(si)21(en)19.9(t)-323.6(o)0(r)-318.7(p)0(e)19.9(r)0(m)19.9(a)0(n)19.9(e)0(n)19.9(t)]TJ
T*
[(hy)21.1(po)21.1(th)20.9(yr)21.1(oi)15.1(di)20.9(sm)-313.9(of)-312.9(va)19.9(ri)20.9(ab)19.9(le)]TJ
0 -1.0077 TD
[(se)20(ve)19.9(ri)20.9(ty)20.9(,)-325.9(h)0(i)20.9(g)0(h)-312.9(s)0(e)14.3(r)0(u)21(m)-324.6(Tg)]TJ
11.7705 4.0483 TD
[(AD,)-335.2(AR)]TJ
/F5 1 Tf
-30.9522 -5.0618 TD
(DUOXA2)Tj
/F3 1 Tf
4.221 0 TD
[(\(612772\))-675.9(Dual)-334.4(oxydase)]TJ
5.3324 -1.0135 TD
[(associated)-337.1(protein:)]TJ
T*
[(a)-336.2(endoplasmic)]TJ
0 -1.0077 TD
(reticulum)Tj
0 -1.0135 TD
[(chaperone)-336.1(protein)]TJ
8.6321 4.0483 TD
[(Pa)14.3(rt)20.9(ia)19.7(l)-323.6(o)0(r)-312.9(c)0(o)19.9(m)0(p)19.9(l)0(e)19.7(t)0(e)-314.3(i)0(o)15.1(d)0(i)20.9(d)0(e)]TJ
.9962 -1.0135 TD
[(or)21.1(ga)19.9(ni)20.9(c)20.1(at)13.9(io)20.9(n)-254.4(d)0(e)14.1(f)0(e)19.9(c)0(t)19.7(,)-256.8(go)21.1(it)14.9(er)19.9(,)]TJ
T*
[(tr)20.9(an)19.9(si)21(en)19.9(t)-323.6(o)0(r)-318.7(p)0(e)19.9(r)0(m)19.9(a)0(n)19.9(e)0(n)19.9(t)]TJ
0 -1.0077 TD
[(hy)21.1(po)21.1(th)20.9(yr)21.1(oi)15.1(di)20.9(sm)-313.9(of)-312.9(va)19.9(ri)20.9(ab)19.9(le)]TJ
0 -1.0135 TD
[(se)20(ve)19.9(ri)20.9(ty)20.9(,)-325.9(h)0(i)20.9(g)0(h)-312.9(s)0(e)14.3(r)0(u)21(m)-324.6(Tg)]TJ
11.7705 4.0483 TD
(AR)Tj
/F5 1 Tf
-30.9522 -5.0618 TD
(TPO)Tj
/F3 1 Tf
2.217 0 TD
[(\(606765\))-2679.9(Thyroid)-330.7(peroxidase:)]TJ
7.3364 -1.0077 TD
(iodide)Tj
0 -1.0135 TD
[(organication)-333.4(and)]TJ
T*
[(thyronine)-332.9(coupling)]TJ
8.6321 3.0348 TD
[(Complete)-341(iodide)]TJ
.9962 -1.0077 TD
[(organication)-333.4(defect,)]TJ
0 -1.0135 TD
[(severe)-337.5(hypothyroidism,)]TJ
T*
[(goiter,)-333.3(high)-332.4(serum)-335.4(Tg)]TJ
11.7705 3.0348 TD
(AR)Tj
/F5 1 Tf
-30.9522 -4.0483 TD
(TG)Tj
/F3 1 Tf
1.6066 0 TD
[(\(188450\))-3290.3(Tg:)-332.6(glycoprotein)]TJ
7.9468 -1.0077 TD
[(precursor)-333.6(to)-336.2(the)]TJ
0 -1.0135 TD
[(thyroid)-335.5(hormones)]TJ
8.6321 2.0212 TD
[(High)-339(iodide)-329.9(uptake,)-340.1(variable)]TJ
.9962 -1.0077 TD
[(hypothyroidism,)-335.5(congenital)]TJ
0 -1.0135 TD
[(or)-330.2(rapidly)-336.7(growing)-336.2(goiter,)]TJ
T*
[(low)-332.2(serum)-335.4(Tg)]TJ
11.7705 3.0348 TD
(AR)Tj
/F5 1 Tf
-30.9522 -4.0483 TD
(IYD/DEHAL)Tj
/F3 1 Tf
.9905 -1.0077 TD
(\(612025\))Tj
7.5725 1.0077 TD
(Dehalogenase)Tj
.9905 -1.0077 TD
[(providing)-331.7(iodide)]TJ
0 -1.0135 TD
[(salvage)-332.9(in)-336.2(thyroid)]TJ
8.6321 2.0212 TD
[(Conserved)-340.3(iodide)-335.7(uptake,)]TJ
.9962 -1.0077 TD
[(negative)-334.3(perchlorate)]TJ
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[(discharge)-334.9(test,)-336.9(goiter,)]TJ
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[(ble)-332.9(tra)12.7(nsm)12.9(iss)14.2(ion)-331.7(thr)13.9(oug)14(h)-340.9(ger)12.8(mli)12.5(ne)-337.4(mo)13.9(sai)12.9(cis)12.9(m\).)-335.1(In)-336.2(suc)13(h)]TJ
T*
[(cir)12.7(cum)11.6(sta)12.9(nc)13.9(es,)-352.2(the)-355.9(dis)14(cus)13(sio)14(n)-358.2(o)0(f)-359.3(the)-350.2(pre)12.9(nat)12.7(al)-354.8(dia)12.7(gno)14(sis)]TJ
0 -1.1174 TD
[(sho)14.2(uld)-504.5(be)-516(ope)12.8(n.)-511.4(The)-506.8(the)12.7(rap)12.9(eut)12.7(ic)-510.3(man)11.6(ag)13.9(eme)10.4(nt)-514.9(of)-509(af-)]TJ
0 -1.1116 TD
[(fec)11.7(ted)-344.4(fet)18.5(use)13(s)-352.2(sho)14.2(uld)-343.3(com)11.6(ply)-337.5(wit)12.8(h)-352.4(the)-344.4(law)11.8(s)-352.2(i)0(n)-342.1(for)14(ce)-350.1(in)]TJ
T*
[(the)-309.9(cou)12.8(ntr)13.9(y)-323.6(c)0(o)13.9(nce)11.7(rne)12.8(d)-317.9(\(1/)]TJ
/F4 1 Tf
10.3963 0 TD
(++)Tj
/F3 1 Tf
1.0943 0 TD
[(0\).)-310.9(The)-316.7(fa)14(mil)12.5(ial)-315.7(re)14(cur)12.8(ren)12.9(ce)]TJ
-11.4906 -1.1174 TD
[(of)-370.8(CH)-372.7(due)-367.3(to)-370.9(dys)14.2(gen)12.8(esi)12.9(s)-375.3(\(2%)-367.2(of)-370.8(fam)11.6(il)14.8(ial)-367.6(occ)11.7(urr)14(enc)11.7(es\))]TJ
0 -1.1116 TD
[(req)12.8(uir)13.9(es)-417.9(fur)14(the)12.7(r)-421.5(stu)14(dy)-411.1(to)-417(det)12.7(erm)11.6(ine)-413.5(the)-413.5(fe)14(asi)12.9(bil)13.7(ity)-412.5(and)]TJ
T*
[(cli)12.6(nic)12.7(al)-320.3(rel)12.7(eva)11.7(nce)-322.4(for)-320(ant)12.7(en)13.9(ata)11.5(l)-329.5(det)12.7(ect)11.5(ion)13.9(.)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 69.7323 572.9951 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 78.633 571.7479 Tm
[(For)-348.7(the)-350.2(evaluation)-349(of)-347.8(fetal)-353.6(thyroid)-347.8(volume,)-346.6(we)-349.8(recom-)]TJ
0 -1.1174 TD
[(mend)-369.7(ultrasound)-375.1(scans)-376.1(at)-366.4(20)-370.8(to)-370.9(22)-370.8(weeks)-371.4(gestation)-375.3(to)]TJ
0 -1.1116 TD
[(detect)-425.1(fetal)-422.8(thyroid)-416.9(hypertrophy)-422.3(and)-424.9(potential)-421.7(thyroid)]TJ
T*
[(dysfunction)-243.7(in)-244.2(the)-246.5(fetus.)-246.2(Goiter)-245(or)-244.1(an)-239.5(absence)-248.3(of)-244.1(thyroid)]TJ
0 -1.1174 TD
[(tissue)-664.2(can)-662.2(also)-662.1(be)-660(documented)-666.7(by)-658.8(this)-661.1(technique.)]TJ
0 -1.1116 TD
[(Measurements)-244.4(should)-242.7(be)-233.7(made)-244.1(as)-239.3(a)-238.4(function)-240.6(of)-238.3(GA,)-237.8(and)]TJ
T*
[(thyroid)-347.8(perimeter)-348.9(and)-344.3(diameter)-347.8(should)-346.4(be)-348.9(measured)-347.4(to)]TJ
0 -1.1174 TD
[(document)-335.1(goiter)-336.3(\(1/)]TJ
/F4 1 Tf
8.0866 0 TD
(+++)Tj
/F3 1 Tf
1.653 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 69.7323 485.3479 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 78.633 484.0439 Tm
[(If)-572.3(a)-566.7(\(large\))-574.5(fetal)-572.5(goiter)-566.7(is)-572.3(diagnosed,)-568.5(prenatal)-577(care)]TJ
0 -1.1116 TD
[(should)-369.4(be)-372(provided)-372.9(in)-370.9(a)-376.6(specialized)-375.2(center)-373.1(of)-370.8(prenatal)]TJ
0 -1.1174 TD
[(care)-336.2(\(1/)]TJ
/F4 1 Tf
3.1275 0 TD
(+++)Tj
/F3 1 Tf
1.653 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 69.7323 452.466 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 78.633 451.1621 Tm
[(We)-443.4(recommend)-447.8(cordocentesis,)-454.2(rather)-441(than)-449.2(amniocen-)]TJ
0 -1.1116 TD
[(tesis,)-246.1(as)-245.1(the)-246.5(reference)-251.8(method)-245.3(for)-245.1(assessing)-253.5(fetal)-244.2(thyroid)]TJ
T*
[(function.)-295.9(Norms)-295.4(have)-300.5(been)-294.7(established)-297.8(as)-296.9(a)-296(function)-292.4(of)]TJ
0 -1.1174 TD
[(GA.)-485.4(This)-483.6(examination)-483.8(should)-484.6(be)-481.4(carried)-483.6(out)-481.5(only)-482.6(if)]TJ
0 -1.1116 TD
[(prenatal)-335.1(interventio)-9.2(n)-329.4(i)0(s)-336.2(considered)-337(\(1/)]TJ
/F4 1 Tf
15.557 0 TD
(+++)Tj
/F3 1 Tf
1.653 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 69.7323 397.644 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 78.633 396.3968 Tm
[(In)-226.8(mo)19.6(st)-226.8(ca)18.5(se)19.9(s,)-223.2(fe)14(ta)19.6(l)-231.6(t)0(h)15(y)0(r)20.9(o)0(i)20.7(d)-237.2(fu)20.9(nc)19.7(ti)20.6(on)-226.8(ca)18.5(n)-237.2(b)0(e)-228(i)0(n)20.7(f)0(e)19.7(r)0(r)20.9(e)0(d)-228(f)0(r)20.9(o)0(m)]TJ
0 -1.1174 TD
[(co)19.7(nt)20.7(ex)19.7(t)-266.2(a)0(n)19.7(d)-266(ul)20.7(tr)15(as)19.9(ou)20.8(nd)-255.6(cr)19.7(it)20.6(er)14(ia)19.6(,)-262.6(a)0(n)19.7(d)-266(fe)19.7(ta)19.6(l)-266.2(b)0(l)14.9(o)0(o)20.8(d)-266(sa)19.9(mp)19.6(li)20.6(ng)]TJ
0 -1.1116 TD
[(is)20.9(,)-326(t)0(h)20.7(e)0(r)19.7(e)0(f)19.7(o)0(r)15.1(e)0(,)-311(o)0(n)20.8(l)0(y)-313.3(e)0(x)13.9(c)0(e)18.5(p)0(t)20.7(i)0(o)20.7(n)0(a)19.7(l)0(l)20.6(y)-323.6(re)14(qu)20.8(ir)20.7(ed)-314.4(\(2)20.9(/)]TJ
/F4 1 Tf
17.7053 0 TD
(++)Tj
/F3 1 Tf
1.0886 0 TD
[(0\))20.9(.)]TJ
/F13 1 Tf
7.9702 0 0 7.9702 69.7323 364.8188 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 78.633 363.5149 Tm
[(We)-702.5(strongly)-694.2(recommend)-707(fetal)-699.2(treatment)-700.4(by)-699.1(intra-)]TJ
0 -1.1174 TD
[(amniotic)-243.1(LT4)-241.8(injections)-244.1(in)-244.2(a)-238.4(euthyroid)-247.5(pregnant)-241.6(woman)]TJ
0 -1.1116 TD
[(with)-483.6(a)-480.3(large)-480.2(fetal)-486.1(goiter)-480.3(associated)-487.8(with)-483.6(hydramnios)]TJ
T*
[(and/or)-480.2(tracheal)-480.2(occlusion;)-480.1(in)-480.4(a)-474.6(hypothyroid)-478.9(pregnant)]TJ
T*
[(woman,)-329(we)-326.8(recommend)-332.6(to)-324.9(treat)-330.6(the)-327.1(woman)-331.3(\(rather)-326.9(the)]TJ
0 -1.1174 TD
[(fetus\))-335.9(with)-333.8(LT4)-334(\(1/)]TJ
/F4 1 Tf
7.9081 0 TD
(++)Tj
/F3 1 Tf
1.1059 0 TD
(0\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 69.7323 299.055 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 78.633 297.7511 Tm
[(For)-366(goitrous)-365.9(nonimmune)-365(fetal)-365.2(hypothyroidism)-368.2(leading)]TJ
0 -1.1116 TD
[(to)-543.7(hydramnios,)-546.6(we)-545.6(recommend)-545.7(intra-amniotic)-550.6(injec-)]TJ
0 -1.1174 TD
[(tions)-408.7(of)-411.1(LT4)-408.9(to)-405.5(decrease)-417.6(the)-407.8(size)-409.8(of)-411.1(the)-407.8(fetal)-411.2(thyroid)]TJ
0 -1.1116 TD
[(gland.)-453.7(The)-454.9(injections)-457.2(should)-455.8(be)-458.4(performed)-456.9(by)-451.5(multi-)]TJ
T*
[(disciplinary)-338.4(specialist)-337.2(teams)-337.3(\(1/)]TJ
/F4 1 Tf
12.9421 0 TD
(+++)Tj
/F3 1 Tf
1.653 0 TD
(\).)Tj
/F13 1 Tf
7.9702 0 0 7.9702 69.7323 244.233 Tm
()Tj
/F3 1 Tf
9.843 0 0 9.843 78.633 242.929 Tm
[(The)-495.2(expert)-498.6(panel)-491.8(proposes)-499.1(the)-494.2(use)-493.8(of)-491.7(10)]TJ
/F14 1 Tf
17.8205 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
[(g/kg)-494.1(esti-)]TJ
-18.3735 -1.1116 TD
[(mated)-435.4(fetal)-434.3(weight)-429.4(per)-436.4(15)-428.4(days)-431.6(in)-434.3(the)-430.8(form)-431.8(of)-434.1(intra-)]TJ
T*
[(amniotic)-583(injections.)-575.8(The)-581.6(risks)-575.4(to)-578.3(the)-580.6(fetus)-576.8(and)-574.7(the)]TJ
0 -1.1174 TD
[(psychological)-288.7(burden)-284.2(on)-284.4(the)-286.8(parents)-286.4(should)-283(be)-285.6(factored)]TJ
0 -1.1116 TD
[(into)-333(the)-338.7(riskbenet)-336.9(evaluation)-337.4(\(2/)]TJ
/F4 1 Tf
14.1574 0 TD
(+)Tj
/F3 1 Tf
.5529 0 TD
(00\).)Tj
/F12 1 Tf
8.9663 0 0 8.9663 69.7323 166.1669 Tm
(Evidence.)Tj
/F3 1 Tf
9.843 0 0 9.843 118.9417 166.1669 Tm
[(Antenatal)-469.7(diagnostics)-469.5(is)-462.9(advised)-470.8(in)-463.1(case)-468.5(of)]TJ
-6.0131 -1.1116 TD
[(fortuitously)-387.9(discovered)-383(fetal)-382.4(goiter)-382.4(during)-381.1(fetal)-382.4(US)-383.1(exami-)]TJ
0 -1.1174 TD
[(nation)-215.4(in)-209.7(an)-210.7(anti-)]TJ
/F5 1 Tf
6.7158 0 TD
(TSHR)Tj
/F3 1 Tf
2.5919 0 TD
[(antibodies)-215.1(negative)-214.1(mother,)-208.4(an)-210.7(earlier)]TJ
-9.3077 -1.1116 TD
[(child)-191.2(with)-189.8(primary)-194.5(CH)-188.4(due)-188.8(to)-186.6(dyshormonogenesis)-194.6(\(and)-189.8(a)-192.3(25%)]TJ
T*
[(risk)-488.1(of)-486(recurrence\),)-487.8(and)-488.3(in)-486.1(an)-487.2(earlier)-483.7(child)-490.7(with)-483.6(\(severe\))]TJ
0 -1.1174 TD
[(syndromic)-236.8(CH.)-232.2(How)-235.4(to)-232.7(evaluate)-238.4(fetal)-232.7(thyroid)-238.3(function)-234.8(and)-229.1(to)]TJ
0 -1.1116 TD
[(manage)-414.5(\(nonautoimmune\))-413.2(fetal)-417(hypothyroidism)-408.5(have)-415.7(been)]TJ
T*
[(described)-261(in)-261.5(the)-258(2014)-252.1(CH)-263.3(concensus)-260.7(guidelines)-255.4(\(1\).)-260.1(In)-255.6(short,)]TJ
0 -1.1174 TD
[(fetal)-319.1(thyroid)-319(size)-317.7(can)-316.7(be)-314.4(assessed)-322.5(by)-313.2(US)-313.9(at)-314.5(20)-319(to)-313.4(22)-313.2(weeks,)]TJ
0 -1.1116 TD
[(and)-194.5(at)-193.6(32)-192.3(weeks)-192.8(gestation.)-194.4(When)-192.1(thyroid)-192.2(measurement)-197.7(values)]TJ
T*
[(based)-249.5(on)-244.1(diameter)-249.9(or)-244.1(perimeter)-245.2(are)-247.5(above)-244(the)-246.5(95th)-246.4(percentile)]TJ
25.5097 67.9242 TD
[(\(238\),)-193.2(the)-188.9(mother)-193.4(and)-194.5(fetus)-190.9(should)-196.6(be)-193.4(referred)-190.7(to)-192.4(a)-192.3(specialized)]TJ
0 -1.1174 TD
[(center)-188.7(for)-181.8(prenatal)-191.1(care.)-189.8(If)-180.7(prenatal)-191.1(intervention)-188.8(is)-186.4(considered,)]TJ
0 -1.1116 TD
[(cordocentesis)-289.5(can)-287.9(be)-291.4(performed)-289.8(to)-284.6(assess)-290.4(fetal)-290.3(thyroid)-284.4(func-)]TJ
T*
[(tion.)-215.4(Conditions)-219.6(that)-218.9(may)-218.8(be)-222.2(a)-215.4(reason)-221.8(for)-216.3(fetal)-221.2(treatment)-222.4(are)-224.5(a)]TJ
T*
[(large)-376.5(fetal)-376.7(goiter)-370.9(with)-379.9(progressive)-377(hydramnios,)-373.9(and)-373.1(risk)-378.7(of)]TJ
0 -1.1174 TD
[(premature)-337.2(delivery)-339.7(or)-336.2(concerns)-340.4(about)-340.9(tracheal)-336.2(occlusion.)-344(If)]TJ
0 -1.1116 TD
[(fetal)-238.4(treatment)-245.4(is)-238.3(considered)-239(in)-238.5(a)-238.4(euthyroid)-241.7(pregnant)-241.6(woman,)]TJ
T*
[(one)-327(way)-322.1(is)-330.4(to)-324.9(administer)-325.8(intra-amniotic)-331.8(LT4)-328.2(injections)-324.7(in)-324.9(a)]TJ
0 -1.1174 TD
[(dosage)-308.2(of)-307.4(10)]TJ
/F14 1 Tf
5.3968 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
[(g/kg)-304(estimated)-314.3(fetal)-313.3(weight)-308.4(per)-309.7(15)-307.5(days.)-308.3(Stu-)]TJ
-5.9498 -1.1116 TD
[(dies)-575.7(have)-582.7(conrmed)-576.6(the)-580.6(feasibility)-579.3(and)-574.7(safety)-579(of)-578.1(intra-)]TJ
T*
[(amniotic)-341.1(LT4)-339.8(injection)-341.1(and)-338.5(strongly)-342.9(suggest)-336.9(that)-339.9(this)-338.5(treat-)]TJ
0 -1.1174 TD
[(ment)-197(is)-198(effective)-204.8(for)-199.1(decreasing)-199.9(goiter)-203.8(size.)-200.2(However,)-199.5(none)-201.4(of)]TJ
0 -1.1116 TD
[(the)-200.4(many)-202.6(LT4)-201.5(regimens)-208.1(used)-201.2(ensures)-205.4(euthyroidism)-205.8(at)-199.3(birth.)-205(It)]TJ
T*
[(is,)-316.6(therefore,)-327.9(not)-320.2(possible)-320.9(to)-319.1(formulate)-324.7(guidelines)-324.6(from)-322.3(cur-)]TJ
T*
[(rent)-316.7(data.)-315.6(These)-314.1(further)-314.2(diagnostics)-319.7(and)-315.5(intervention)-315.5(should)]TJ
0 -1.1174 TD
[(only)-304(be)-308.6(done)-305.1(by)-307.5(an)-308.6(experienced)-311.8(multidisciplinary)-311(team)-313.4(in)-301.8(a)]TJ
0 -1.1116 TD
[(specialized)-231.2(center)-229.1(of)-221(prenatal)-231.4(care)-226.7(after)-226.8(a)-226.9(careful)-230.1(benetrisk)]TJ
T*
[(evaluation.)-513.7(Determination)-515.7(of)-509(the)-511.4(indications)-515.9(and)-511.3(optimal)]TJ
0 -1.1174 TD
[(modes)-393.6(of)-399.6(prenatal)-398.4(treatment)-400.9(for)-394.9(nonimmune)-399.6(fetal)-394(goitro)-6.8(us)]TJ
0 -1.1116 TD
[(hypothyroidism)-212.6(will)-218.8(require)-211.7(larger)-216.3(well-designed)-220.4(studies)-216.1(that)]TJ
T*
[(would)-357.8(be)-366.2(best)-362.6(conducted)-364.9(through)-359.1(international)-364(cooperation)]TJ
0 -1.1174 TD
[(between)-346.3(multidisciplinary)-351.3(medical)-352.5(teams.)-346.5(Alternative)-351(ways)]TJ
0 -1.1116 TD
[(of)-399.6(treating)-403.1(the)-407.8(fetus)-398.2(by)-405.4(administering)-404.1(drugs)-402.7(to)-399.7(the)-402(mother)]TJ
T*
[(should)-340.6(also)-339.6(be)-343.2(investigated.)-343(In)-336.2(a)-342.1(hypothyroid)-340.7(pregnant)-345.3(wo-)]TJ
0 -1.1174 TD
[(man,)-187.7(the)-183.1(preferred)-191.8(approach)-185.1(is)-186.4(to)-186.6(treat)-186.6(the)-188.9(woman)-187.3(with)-184.1(\(rather)]TJ
0 -1.1116 TD
[(than)-454.9(the)-459.6(fetus\))-456.9(with)-460.5(LT4.)-458.4(Finally,)-456(adequ)-7.8(ate)-455(iodine)-457.3(intake)]TJ
T*
[(should)-277.2(be)-285.6(ensured)-280.5(for)-279.7(all)-281.2(pregnant)-287.7(women)-279.5(\(250)]TJ
/F14 1 Tf
19.3238 0 TD
(l)Tj
/F3 1 Tf
.5529 0 TD
(g/day\).)Tj
/F6 1 Tf
8.9663 0 0 8.9663 310.8472 418.2235 Tm
(CONCLUSIONS)Tj
/F3 1 Tf
9.843 0 0 9.843 320.8251 401.7826 Tm
.0119 Tc
[(Thi)4.9(s)-363.4(up)5(date)-364.7(o)5(f)-363.5(th)5(e)-364.7(c)-1.9(o)5(n)-.7(sens)5.2(us)-363.4(g)5(u)-.7(id)5(el)4.9(in)5(es)-363.4(o)5(n)-363.6(CH)-364.5(r)5.1(e)-1.9(com-)]TJ
-1.0137 -1.1116 TD
.0117 Tc
[(men)4.8(d)-.9(s)-421.2(w)4(orl)4.7(dwid)4.8(e)-422.5(n)-.9(eonatal)-421.5(s)-.7(creeni)4.7(ng)-421.4(and)-421.4(a)3.7(pp)4.8(ro)4.8(pri)4.7(at)4.7(e)-422.5(d)-.9(i)4.7(-)]TJ
0 -1.1174 TD
.0119 Tc
[(agn)5(o)-.7(st)4.9(icsin)5(clu)5(d)-.7(i)4.9(n)-.7(g)-277.2(g)-.7(enet)4.9(icsto)-277.2(ass)5.2(e)-1.9(s)5.2(s)-282.7(th)5(e)-284.1(c)3.9(au)5(se)-284.1(o)5(f)-282.9(b)5(o)-.7(t)4.9(h)]TJ
0 -1.1116 TD
.0073 Tc
[(pr)-5.3(i)-5.4(m)-.8(ar)-5.3(y)-293.3(a)-.7(n)-5.3(d)-293.3(ce)-6.5(nt)-5.4(r)-5.3(a)-.7(l)-293.4(h)-5.3(yp)-5.3(ot)-5.4(hy)-5.3(r)-5.3(o).4(i)-5.4(d).4(i)-5.4(s).6(m)-6.5(.)-289.9(T)-6.5(h).4(e)-294.5(e)-6.5(xp)-5.3(er)-5.3(t)-293.4(p).4(a)-6.5(n).4(e)-6.5(l)-293.4(re)-6.5(c-)]TJ
T*
[(om)-6.4(me)-6.4(nd)-5.2(s)-615.6(t)-5.3(he)-616.9(i)-5.3(m)-.7(m)-6.4(e)-.6(d)-5.2(i).4(a)-6.4(t).4(e)-616.9(s)-5(t)-5.3(a)-.6(r)-5.2(t)-615.9(of)-621.5(co)-5.2(rr)-5.2(ec)-6.4(tl)-5.3(y)-615.7(d)-5.2(os)-5(ed)-621.5(LT4)]TJ
0 -1.1174 TD
.0116 Tc
[(t)4.6(r)-1(eatment,)-613.9(an)4.7(d)-623.1(f)4.8(requent)-617.4(f)4.8(o)-1(ll)]TJ
12.3488 0 TD
.012 Tc
[(ow-u)5.1(p)-622.7(i)5(nclu)5.1(din)5.1(g)-616.9(labor)5.2(at)5(or)5.2(y)]TJ
-12.3488 -1.1116 TD
[(t)4.9(e)-1.9(st)4.9(in)5(g)-455.7(a)-1.9(n)5(d)-455.7(do)5(se)-456.9(adj)4.9(u)-.7(s)5.2(t)-.8(men)5(t)]TJ
11.9744 0 TD
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[(s)-458.9(t)-4.2(o)-453.4(k)-4.1(ee)-5.3(p)-459.1(T).4(H)-460(l)-4.2(evels)-458.9(i)1.5(n)-459.1(t)-4.2(he)-5.3(ir)]TJ
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[(encing)-514.9(the)-510.3(incidence)-517.1(of)-508.8(congenital)-518.6(hypothyroidism)-513.7(de-)]TJ
0 -1.1284 TD
[(tected)-591.8(by)-585.8(neonatal)-592.1(screening.)-588.2(Horm)-589.6(Res)-588(Paediatr)]TJ
/F8 1 Tf
22.1402 0 TD
(83:)Tj
/F3 1 Tf
-22.1402 -1.1284 TD
(8693.)Tj
-1.7505 -1.1223 TD
[(10.)-500.5(Mitchell)-372.5(ML,)-373.6(Hsu)-373.2(HW,)-372.2(Sahai)-371.3(I;)-374.1(Massachusetts)-379.2(Pediatric)]TJ
1.7505 -1.1284 TD
[(Endocrine)-354.9(Work)-354.9(Group)-358.4(2011)-348.2(The)-360.3(increased)-354.4(incidence)-358.5(of)]TJ
0 -1.1223 TD
[(congenital)-244.1(hypothyroidism:)-244.9(fact)-242.5(or)-246.6(fancy?)-241.5(Clin)-248.2(Endocrinol)]TJ
0 -1.1284 TD
[(\(Oxf)-86.1(\))]TJ
/F8 1 Tf
2.6349 0 TD
(75:)Tj
/F3 1 Tf
1.3357 0 TD
(806810.)Tj
-5.7211 -1.1223 TD
[(11.)-500.5(Corbetta)-369.3(C,)-371(Weber)-369.6(G,)-367.7(Cortinovis)-371.9(F,)-369.1(Calebiro)-369.3(D,)-367.8(Passoni)]TJ
1.7505 -1.1284 TD
[(A,)-367.7(Vigone)-372(MC,)-370.4(Beck-Peccoz)-372.3(P,)-369.1(Chiumello)-368(G,)-367.7(Persani)-373(L)]TJ
0 -1.1223 TD
[(2009)-165.3(A)-550.6(7-year)-550.7(experience)-548.8(with)-549.9(low)-544.3(blood)-549.1(TSH)-549.6(cutoff)]TJ
0 -1.1284 TD
[(levels)-373.2(for)-364.9(neonatal)-372.5(screening)-374.6(reveals)-368.2(an)-370.4(unsuspected)-371.7(fre-)]TJ
27.0074 70.8853 TD
[(quency)-558.2(of)-557.6(congenital)-555.2(hypothyroidism.)-562.5(Clin)-553.1(Endocrinol)]TJ
0 -1.1223 TD
[(\(Oxf)-86.1(\))]TJ
/F8 1 Tf
2.6349 0 TD
(71:)Tj
/F3 1 Tf
1.3357 0 TD
(739745.)Tj
-5.7211 -1.1284 TD
[(12.)-500.5(Barry)-362(Y,)-361.6(Bonaldi)-356.5(C,)-358.8(Goulet)-359.3(V,)-361.7(Coutant)-356.5(R,)-358.8(Le)]TJ
20.4263 .0427 TD
()Tj
.3843 -.0427 TD
[(ger)-360.7(J,)-359.2(Paty)]TJ
-19.0601 -1.1223 TD
[(AC,)-415.4(Delmas)-423.7(D,)-410.4(Cheillan)-421.3(D,)-416.5(Roussey)-416.9(M)-414.1(2016)-415.3(Increased)]TJ
0 -1.1283 TD
[(incidence)-474.4(of)-466.1(congenital)-469.8(hypothyroidism)-464.9(in)-469.3(France)-470.1(from)]TJ
0 -1.1223 TD
[(1982)-537.3(to)-530.3(2012:)-530.8(a)-535(nationwide)-534.3(multicenter)-538.3(analysis.)-531.3(Ann)]TJ
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1.7505 -1.1284 TD
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0 -1.1223 TD
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0 -1.1284 TD
[(Zealand)-441.9(from)-443.9(19932010.)-434.4(J)-438.4(Clin)-443.4(Endocrinol)-435.7(Metab)]TJ
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1.7505 -1.1284 TD
[(Hindmarsh)-355.2(P,)-356.9(Cole)-350.6(TJ)-355(2016)-354.3(Dening)-350.7(the)-351.7(newborn)-356.8(blood)]TJ
0 -1.1223 TD
[(spot)-340.7(screening)-338.1(reference)-340.4(interval)-339.5(for)-334.4(TSH:)-335.7(impact)-337.1(of)-338.1(eth-)]TJ
0 -1.1284 TD
[(nicity.)-338.9(J)-334.7(Clin)-333.6(Endocrinol)-332(Metab)]TJ
/F8 1 Tf
13.3451 0 TD
(101:)Tj
/F3 1 Tf
1.8359 0 TD
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1.7505 -1.1284 TD
[(Fugazzola)-374.2(L)-368(2018)-372.6(Genetics)-367.1(and)-370.6(management)-376.7(of)-368.6(congen-)]TJ
0 -1.1223 TD
[(ital)-344.6(hypothyroidism.)-343(Best)-343.6(Pract)-343.1(Res)-344(Clin)-345.8(Endocrinol)-344.2(Me-)]TJ
0 -1.1284 TD
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/F8 1 Tf
1.5675 0 TD
(32:)Tj
/F3 1 Tf
1.3296 0 TD
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[(16.)-500.5(Peters)-671.7(C,)-669.8(Nicholas)-673.9(AK,)-668.3(Schoenmakers)-675.1(E,)-673(Lyons)-666.5(G,)]TJ
1.7505 -1.1284 TD
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0 -1.1223 TD
[(Schoenmakers)-357.9(N)-349.4(2019)-354.3(DUOX2/DUOXA2)-356.9(mutations)-356.2(fre-)]TJ
0 -1.1284 TD
[(quently)-510.3(cause)-506.5(congenital)-506.4(hypothyroidism)-507.6(which)-512.2(evades)]TJ
9.2951 0 0 9.2951 333.9779 474.1227 Tm
[(detection)-244(on)-244.3(UK)-241.3(newborn)-240.9(screening.)-246.6(Thyroid)]TJ
/F8 1 Tf
18.3953 0 TD
(29:)Tj
/F3 1 Tf
1.3296 0 TD
(790801.)Tj
-21.4754 -1.1284 TD
[(17.)-500.5(Knowles)-324.1(RL,)-318.1(Oerton)-319.5(J,)-322.6(Cheetham)-322.5(T,)-319.3(Butler)-316(G,)-325.1(Cavanagh)]TJ
1.7505 -1.1223 TD
[(C,)-462.4(Tetlow)-458.7(L,)-459.5(Dezateux)-458.1(C)-462.4(2018)-458(Newborn)-455.9(screening)-466.1(for)]TJ
0 -1.1284 TD
[(primary)-460.2(congenital)-463.7(hypothyroidism:)-458.3(estimating)-457.6(test)-460.2(per-)]TJ
0 -1.1223 TD
[(formance)-390(at)-382.1(different)-381.5(TSH)-384.9(thresholds.)-383.3(J)-383.5(Clin)-382.4(Endocrinol)]TJ
0 -1.1284 TD
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/F8 1 Tf
2.8971 0 TD
(103:)Tj
/F3 1 Tf
1.8359 0 TD
(37203728.)Tj
-6.4835 -1.1223 TD
[(18.)-500.5(Dufort)-482.3(G,)-483.6(Larrive)]TJ
8.9232 .0427 TD
()Tj
.3842 -.0427 TD
[(e-Vanier)-483(S,)-478.9(Euge)]TJ
6.947 .0427 TD
(`)Tj
.3843 -.0427 TD
[(ne)-480.2(D,)-483.6(De)-481.8(Deken)-480.4(X,)]TJ
-14.8882 -1.1284 TD
[(Seebauer)-291.6(B,)-279.5(Heinimann)-290.3(K,)-282.4(Le)]TJ
11.8325 .0427 TD
()Tj
.3843 -.0427 TD
[(vesque)-289(S,)-283.7(Gravel)-287.1(S,)-277.6(Szinnai)]TJ
-12.2168 -1.1223 TD
[(G,)-550.7(Van)-555.1(Vliet)-547.6(G,)-550.7(Deladoe)]TJ
10.7712 .0183 TD
()Tj
.3843 -.0183 TD
[(y)-549.1(J)-554.3(2019)-543.4(Wide)-551.4(spectrum)-552.8(of)]TJ
-11.1555 -1.1284 TD
[(DUOX2)-641.4(deciency:)-636.1(from)-633(life-threatening)-645.4(compressive)]TJ
0 -1.1223 TD
[(goiter)-482(in)-475.4(infancy)-474.7(to)-475.4(lifelong)-475.6(euthyroidism.)-481(Thyroid)]TJ
/F8 1 Tf
22.1402 0 TD
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/F3 1 Tf
-22.1402 -1.1284 TD
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-1.7505 -1.1223 TD
[(19.)-500.5(Lain)-274.5(S,)-277.6(Trumpff)-271.7(C,)-279.5(Grosse)-275.6(SD,)-273.2(Olivieri)-275.3(A,)-276.3(Guy)-270.4(Van)-274.6(Vliet)]TJ
1.7505 -1.1284 TD
[(G)-349.4(2017)-342.1(Are)-350.1(lower)-349.8(TSH)-342.2(cutoffs)-350(in)-347.4(neonatal)-348.1(screening)-350.2(for)]TJ
0 -1.1223 TD
[(congenital)-445.4(hypothyroidism)-440.5(warranted?)-444.8(Eur)-437.7(J)-438.4(Endocrinol)]TJ
/F8 1 Tf
0 -1.1284 TD
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/F3 1 Tf
1.8359 0 TD
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-3.5863 -1.1223 TD
[(20.)-500.5(Zwaveling-Soonawala)-477.6(N,)-471.4(van)-468.2(Trotsenburg)-468.3(AS,)-468.4(Verkerk)]TJ
1.7505 -1.1284 TD
[(PH)-468.3(2015)-470.2(The)-464(severity)-473.4(of)-466.1(congenital)-469.8(hypothyroidism)-464.9(of)]TJ
0 -1.1223 TD
[(central)-441.8(origin)-441.2(should)-432.5(not)-439(be)-437.5(underestimated.)-445.2(J)-432.3(Clin)-443.4(En-)]TJ
0 -1.1284 TD
[(docrinol)-335.9(Metab)]TJ
/F8 1 Tf
6.575 0 TD
(100:)Tj
/F3 1 Tf
1.8359 0 TD
(297300.)Tj
-10.1613 -1.1223 TD
[(21.)-500.5(Nebesio)-534.1(TD,)-534.5(McKenna)-532.9(MP,)-533.2(Nabhan)-529.3(ZM,)-532.2(Eugster)-532.5(EA)]TJ
1.7505 -1.1284 TD
[(2010)-390.9(Newborn)-388.8(screening)-386.8(results)-388.9(in)-384(children)-388.9(with)-391.4(central)]TJ
T*
[(hypothyroidism.)-336.9(J)-334.7(Pediatr)]TJ
/F8 1 Tf
10.8261 0 TD
(156:)Tj
/F3 1 Tf
1.8298 0 TD
(990993.)Tj
-14.4064 -1.1223 TD
[(22.)-500.5(Braslavsky)-417.2(D,)-410.4(Me)]TJ
8.9415 .0427 TD
()Tj
.3843 -.0427 TD
[(ndez)-411.5(MV,)-409.9(Prieto)-411.7(L,)-416.9(Keselman)-409.9(A,)-416.5(En-)]TJ
-7.5752 -1.1284 TD
[(acan)-470.6(R,)-468.5(Grun)]TJ
5.3307 .0122 TD
()Tj
.4147 -.0122 TD
[(eiro-Papendieck)-474.8(L,)-465.6(Jullien)-472.2(N,)-465.3(Savenau)-467.9(A,)]TJ
-5.7455 -1.1223 TD
[(Reynaud)-550.9(R,)-547.8(Brue)-548.6(T,)-544.9(Bergada)]TJ
12.4363 .0427 TD
()Tj
.9271 -.0427 TD
[(I,)-551.5(Chiesa)-543.2(A)-550.6(2017)-543.4(Pilot)]TJ
-13.3634 -1.1284 TD
[(neonatal)-403(screening)-405.1(program)-405.9(for)-401.5(central)-399.1(congenital)-402.7(hypo-)]TJ
0 -1.1223 TD
[(thyroidism:)-421.2(evidence)-420(of)-417.4(signicant)-418.8(detection.)-414.8(Horm)-418.8(Res)]TJ
0 -1.1284 TD
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/F8 1 Tf
3.629 0 TD
(88:)Tj
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1.3296 0 TD
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1.7505 -1.1284 TD
[(Y,)-581.2(Hirahara)-580.6(F)-576.4(2012)-573.9(Mass)-575.6(screening)-582(of)-575.9(newborns)-581.7(for)]TJ
0 -1.1223 TD
[(congenital)-402.7(hypothyroidism)-403.9(of)-399.1(central)-405.2(origin)-398.5(by)-402.8(free)-397.9(thy-)]TJ
0 -1.1284 TD
[(roxine)-299.6(measurement)-305.1(of)-301.5(blood)-299(samples)-299.4(on)-299.2(lter)-301.8(paper.)-304.3(Eur)]TJ
0 -1.1223 TD
[(J)-334.7(Endocrinol)]TJ
/F8 1 Tf
5.5137 0 TD
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1.8298 0 TD
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-9.094 -1.1284 TD
[(24.)-500.5(Kempers)-286.5(MJ,)-285.4(Lanting)-280.4(CI,)-288(van)-279.1(Heijst)-284.6(AF,)-285.4(van)-279.1(Trotsenburg)]TJ
1.7505 -1.1223 TD
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0 -1.1284 TD
[(screening)-514.9(for)-505.2(congenital)-506.4(hypothyroidism)-507.6(based)-508.4(on)-506.5(thy-)]TJ
0 -1.1223 TD
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0 -1.1284 TD
[(surement:)-290.1(potentials)-287.3(and)-285.2(pitfalls.)-285.1(J)-279.8(Clin)-284.8(Endocrinol)-289.3(Metab)]TJ
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40.9535 0 TD
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1.7505 -1.1223 TD
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[(22)18(5)24.1(23)18(7.)]TJ
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1.7505 -1.1284 TD
[(Vijlder)-458.7(JJ,)-456(Verkerk)-454.8(PH)-456.1(2005)-458(Clinical)-457.3(effectiveness)-457.7(and)]TJ
0 -1.1223 TD
[(cost-effectiveness)-433(of)-417.4(the)-424.9(use)-424.6(of)-417.4(the)-424.9(thyroxine/thyroxine-)]TJ
0 -1.1284 TD
[(binding)-256(globulin)-249.5(ratio)-250.1(to)-255.9(detect)-250.2(congenital)-256.3(hypothyroidism)]TJ
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1.8359 0 TD
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1.7505 -1.1284 TD
[(Tonduti)-355.5(D,)-355.6(Dica)-357.6(A,)-355.5(Paone)-359.7(L,)-355.9(Rozenkova)-354.2(K,)-355.5(Malikova)-361.4(J,)]TJ
T*
[(van)-456(der)-452.2(Walt)-453.2(A,)-453.1(de)-455.8(Coo)-456.6(IFM,)-450.2(McGowan)-457.1(A,)-453.1(Lyons)-453.1(G,)]TJ
0 -1.1223 TD
[(Aarsen)-457.5(FK,)-450.1(Barca)-453.5(D,)-447(van)-449.9(Beynum)-454.7(IM,)-447.2(van)-449.9(der)-452.2(Knoop)]TJ
0 -1.1284 TD
[(MM,)-297.7(Jansen)-306.4(J,)-298.2(Manshande)-299(M,)-298.3(Lunsing)-300.3(RJ,)-297(Nowak)-300.8(S,)-302(den)]TJ
0 -1.1223 TD
[(Uil)-427.8(CA,)-427.6(Zillikens)-425.1(MC,)-431.4(Visser)-427.5(FE,)-426(Vrijmoeth)-428.1(P,)-424(de)-425.3(Wit)]TJ
0 -1.1284 TD
[(MCY,)-250.1(Wolf)-244.5(NI,)-248.2(Zandstra)-250.2(A,)-245.8(Ambegaonkar)-249.5(G,)-245.8(Singh)-247(Y,)-245.8(de)]TJ
0 -1.1223 TD
[(Rijke)-459.9(YB,)-464.2(Medici)-458.7(M,)-463(Bertini)-461.9(ES,)-456.5(Depoorter)-460.6(S,)-460.5(Lebl)-463.5(J,)]TJ
0 -1.1284 TD
[(Cappa)-404.3(M,)-395.9(De)-396.4(Meirleir)-402.1(L,)-398.6(Krude)-399.2(H,)-398.2(Craiu)-401.8(D,)-398.2(Zibordi)-394.4(F,)]TJ
0 -1.1223 TD
[(Oliver)-404.3(Petit)-402.6(I,)-405.1(Polak)-397.6(M,)-402(Chatterjee)-407.9(K,)-404.3(Visser)-403.1(TJ,)-397.8(Visser)]TJ
0 -1.1284 TD
[(WE)-250.5(2019)-250.6(Effectiveness)-254.1(and)-254.7(safety)-248(of)-252.7(the)-248(tri-iodothyronine)]TJ
0 -1.1223 TD
[(analogue)-446.3(Triac)-445.8(in)-438.9(children)-443.8(and)-437.7(adults)-448.3(with)-440.1(MCT8)-439.6(de-)]TJ
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1.7505 -1.1223 TD
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0 -1.1284 TD
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1.7505 -1.1284 TD
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1.7505 -1.1223 TD
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T*
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22.9209 .0244 TD
()Tj
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T*
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0 -1.1284 TD
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15.3579 .0427 TD
()Tj
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1.7505 -1.1223 TD
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1.7505 -1.1223 TD
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(7:)Tj
/F3 1 Tf
.8356 0 TD
(90189032.)Tj
-19.4383 -1.1223 TD
[(53.)-500.5(Trumpff)-247.3(C,)-242.9(de)-242.4(Schepper)-244.7(J,)-243.3(Vanderfauillie)-248.5(J,)-243.3(Vercruysse)-250.3(N,)]TJ
1.7505 -1.1284 TD
[(Van)-262.4(Oyen)-256.4(H,)-258(Moreno-Reyes)-266.1(R,)-255.1(Tafforeau)-266.7(J,)-255.5(Vandevijvere)]TJ
0 -1.1223 TD
[(S)-350.7(2016)-348.2(Neonatal)-349.7(thyroid-stimulating)-353.9(hormone)-354.8(concentra-)]TJ
0 -1.1284 TD
[(tion)-255.6(and)-254.7(psychomotor)-256.3(development)-256.6(at)-254(preschool)-254.6(age.)-259(Arch)]TJ
0 -1.1223 TD
[(Dis)-336(Child)]TJ
/F8 1 Tf
4.2817 0 TD
(101:)Tj
/F3 1 Tf
2.1652 0 TD
(11001106.)Tj
-8.1974 -1.1284 TD
[(54.)-500.5(Cherella)-245.4(CE,)-244.9(Wasser)-246(AJ)-244.9(2017)-238.5(Congenital)-244.7(hypothyroidism:)]TJ
1.7505 -1.1223 TD
[(insights)-540.5(into)-542.3(pathogenesis)-542.1(and)-541.4(treatment.)-544.8(Int)-538.9(J)-536(Pediatr)]TJ
0 -1.1284 TD
(Endocrinol)Tj
/F8 1 Tf
4.794 0 TD
(2017:)Tj
/F3 1 Tf
2.3299 0 TD
(11.)Tj
-8.8744 -1.1284 TD
[(55.)-500.5(Leung)-378.9(AKC,)-374.4(Leung)-378.9(AAC)-380.4(2019)-372.6(Evaluation)-382.1(and)-376.7(manage-)]TJ
1.7505 -1.1223 TD
[(ment)-406.3(of)-399.1(the)-406.6(child)-406.3(with)-403.6(hypothyroidism.)-404(World)-403.3(J)-401.8(Pediatr)]TJ
/F8 1 Tf
0 -1.1284 TD
(15:)Tj
/F3 1 Tf
1.3357 0 TD
(124134.)Tj
-3.0862 -1.1223 TD
[(56.)-500.5(van)-541.4(Tijn)-538(D,)-538.5(de)-535.1(Vijder)-538.5(JJM,)-540.8(Verbeeten)-546(B,)-535.6(Verkerk)-540.2(P,)]TJ
1.7505 -1.1284 TD
[(Vulsma)-443.9(T)-441.2(2005)-439.7(Neonatal)-441.2(detection)-445.2(of)-435.6(congenital)-445.4(hypo-)]TJ
0 -1.1223 TD
[(thyroidism)-305.7(of)-307.6(central)-307.6(origin.)-307.1(J)-304.2(Clin)-309.2(Endocrinol)-307.6(Metab)]TJ
/F8 1 Tf
22.1402 0 TD
(90:)Tj
/F3 1 Tf
-22.1402 -1.1284 TD
(33503359.)Tj
-1.7505 -1.1223 TD
[(57.)-500.5(Salm)-519(N,)-520.2(Yetter)-524.4(E,)-520.5(Tluczek)-521.2(A)-520.1(2012)-519(Informing)-519.6(parents)]TJ
1.7505 -1.1284 TD
[(about)-504.5(positive)-509(newborn)-509.3(screen)-509(results:)-510.4(parents)-506.8(recom-)]TJ
0 -1.1223 TD
[(mendations.)-336.8(J)-334.7(Child)-333.7(Health)-333(Care)]TJ
/F8 1 Tf
13.7294 0 TD
(16:)Tj
/F3 1 Tf
1.3296 0 TD
(367381.)Tj
-16.8095 -1.1284 TD
[(58.)-500.5(Cassio)-251.5(A,)-251.9(Corbetta)-253.4(C,)-249(Antonozzi)-254.1(I,)-246.5(Calaciura)-255.9(F,)-247.1(Caruso)-255.3(U,)]TJ
1.7505 -1.1223 TD
[(Cesaretti)-366.1(G,)-361.6(Gastaldi)-362.3(R,)-364.9(Medda)-362.2(E,)-362(Mosca)-361.3(F,)-356.9(Pasquini)-366.1(E,)]TJ
0 -1.1284 TD
[(Salerno)-611.8(MC,)-614.3(Stoppioni)-612.4(V,)-611.7(Tonacchera)-612.2(M,)-615.5(Weber)-613.5(G,)]TJ
0 -1.1223 TD
[(Olivieri)-513.2(A;)-513.6(Italian)-516.3(Society)-511.3(for)-511.3(Pediatric)-517.6(Endocrinology)]TJ
0 -1.1284 TD
[(and)-407.2(Diabetology;)-405.9(Italian)-412.6(Society)-407.6(for)-407.6(the)-406.6(Study)-405.6(of)-405.2(Meta-)]TJ
0 -1.1223 TD
[(bolic)-430.7(Diseases)-433(and)-425.5(Neonatal)-435.1(Screening;)-432.9(Italian)-430.9(National)]TJ
0 -1.1284 TD
[(Institute)-419.4(of)-423.5(Health;)-424(Italian)-418.7(National)-424.2(Coordinating)-420(Group)]TJ
0 -1.1223 TD
[(for)-352.7(Congenital)-354.5(Hypothyroidism;)-350.1(Italian)-357.7(Thyroid)-352.3(Associa-)]TJ
0 -1.1284 TD
[(tion;)-651.6(Italian)-656.5(Society)-651.6(of)-649.1(Pediatrics;)-656.7(Italian)-656.5(Society)-651.6(of)]TJ
0 -1.1223 TD
[(Neonatology;)-546.8(Italian)-540.7(Society)-541.8(of)-539.3(Endrocrinology;)-547.9(Asso-)]TJ
0 -1.1284 TD
[(ciazione)-260.8(Medici)-263.6(Endocrinologi)-264.8(2013)-256.7(The)-262.7(Italian)-260.1(screening)]TJ
0 -1.1223 TD
[(program)-418.1(for)-413.7(primary)-417.5(congenital)-421(hypothyroidism:)-415.6(actions)]TJ
0 -1.1284 TD
[(to)-420.6(improve)-421.3(screening,)-423.5(diagnosis,)-417.4(follow-up,)-421.2(and)-425.5(surveil-)]TJ
0 -1.1223 TD
[(lance.)-336.1(J)-334.7(Endocrinol)-332(Invest)]TJ
/F8 1 Tf
10.9969 0 TD
(36:)Tj
/F3 1 Tf
1.3357 0 TD
(195203.)Tj
-14.0831 -1.1284 TD
[(59.)-500.5(Hettiarachchi)-439.3(M,)-426.4(Amarasena)-441.6(S)-430(2014)-427.5(Indicators)-433.3(of)-435.7(new-)]TJ
1.7505 -1.1223 TD
[(born)-692.1(screening)-697.9(for)-688.2(congenital)-695.5(hypothyroidism)-696.6(in)-688.9(Sri)]TJ
0 -1.1284 TD
[(Lanka:)-718.1(program)-716.9(challenges)-723.8(and)-718.3(way)-713.7(forward.)-721.3(BMC)]TJ
0 -1.1223 TD
[(Health)-339.1(Serv)-333.3(Res)]TJ
/F8 1 Tf
7.008 0 TD
(14:)Tj
/F3 1 Tf
1.3357 0 TD
(385.)Tj
-10.0942 -1.1284 TD
[(60.)-500.5(Supakul)-617.5(N,)-611.7(Delaney)-618.5(LR,)-617(Siddiqui)-612.3(AR,)-616.6(Jennings)-612.9(SG,)]TJ
1.7505 -1.1223 TD
[(Eugster)-459.3(EA,)-455.2(Karmazyn)-462.5(B)-456.3(2012)-458(Ultrasound)-458.9(for)-456.4(primary)]TJ
0 -1.1284 TD
[(imaging)-820.9(of)-819.9(congenital)-817.5(hypothyroidism.)-824.8(AJR)-817.1(Am)-818.7(J)]TJ
0 -1.1223 TD
(Roentgenol)Tj
/F8 1 Tf
4.9587 0 TD
(199:)Tj
/F3 1 Tf
1.8298 0 TD
(360366.)Tj
-8.5389 -1.1284 TD
[(61.)-500.5(Chanoine)-355.3(JP,)-350(Toppet)-354.1(V,)-355.5(Lagasse)-355.3(R,)-352.7(Spehl)-354.9(M,)-353.2(Delange)-356.2(F)]TJ
1.7505 -1.1284 TD
[(1991)-250.6(Determination)-253.6(of)-252.7(thyroid)-252.3(volume)-254.1(by)-250.4(ultrasound)-249.9(from)]TJ
0 -1.1223 TD
[(the)-272.4(neonatal)-268.8(period)-269.1(to)-274.2(late)-270.1(adolescence.)-275.5(Eur)-266.9(J)-273.7(Pediatr)]TJ
/F8 1 Tf
21.6401 0 TD
(150:)Tj
/F3 1 Tf
-21.6401 -1.1284 TD
(395399.)Tj
-1.7505 -1.1223 TD
[(62.)-500.5(Perry)-341.8(RJ,)-345.8(Hollman)-340.7(AS,)-346.4(Wood)-340.4(AM,)-342.8(Donaldson)-347.2(MD)-342.7(2002)]TJ
1.7505 -1.1284 TD
[(Ultrasound)-251.5(of)-246.6(the)-248(thyroid)-246.2(gland)-248.3(in)-243.7(the)-248(newborn:)-252.7(normative)]TJ
0 -1.1223 TD
[(data.)-337.8(Arch)-331.9(Dis)-336(Child)-333.7(Fetal)-334.1(Neonatal)-337.5(Ed)]TJ
/F8 1 Tf
16.6265 0 TD
(87:)Tj
/F3 1 Tf
1.3296 0 TD
(F209F211.)Tj
-19.7066 -1.1284 TD
[(63.)-500.5(Freire)-254.1(R,)-255.1(Monte)-259.8(O,)-251.9(Tomimori)-259.5(EK,)-253.9(Catarino)-259.5(RM,)-254.5(Sterza)-256(T,)]TJ
1.7505 -1.1223 TD
[(Rocha)-501.9(T,)-502.2(Pereira)-508.5(KCC,)-505.7(Mattos)-502.4(HS,)-505(Jr.,)-502(Fagundes)-505.6(LB,)]TJ
0 -1.1284 TD
[(Liberato)-518.9(MM,)-511.2(Dos)-513.5(Santos)-518.8(LWR,)-517.8(Pereira)-514.6(A,)-514.1(Cintra)-517.3(T,)]TJ
0 -1.1223 TD
[(Hegner)-379.1(C,)-377.1(Lube)-378.7(D,)-373.8(Murad)-378.6(M)-371.4(2015)-378.7(Sonographic)-380.6(evalua-)]TJ
0 -1.1284 TD
[(tion)-298.3(of)-295.4(the)-296.8(thyroid)-295(size)-294.2(in)-298.6(neonates.)-299.1(J)-292(Clin)-297(Ultrasound)]TJ
/F8 1 Tf
22.1402 0 TD
(43:)Tj
/F3 1 Tf
-22.1402 -1.1223 TD
(224229.)Tj
-1.7505 -1.1284 TD
[(64.)-500.5(Clerc)-369.4(J)-359.1(2014)-366.5(Imaging)-366.4(the)-363.9(thyroid)-368.1(in)-359.6(children.)-370.7(Best)-361.9(Pract)]TJ
1.7505 -1.1223 TD
[(Res)-337.9(Clin)-333.6(Endocrinol)-332(Metab)]TJ
/F8 1 Tf
11.5824 0 TD
(28:)Tj
/F3 1 Tf
1.3357 0 TD
(203220.)Tj
-14.6687 -1.1284 TD
[(65.)-500.5(Keller-Petrot)-377.4(I,)-374.6(Leger)-373.2(J,)-377.5(Sergent-Alaoui)-375.8(A,)-373.8(de)-370.4(Labriolle-)]TJ
1.7505 -1.1223 TD
[(Vaylet)-253.7(C)-248.9(2017)-250.6(Congenital)-250.8(hypothyroidism:)-251(role)-250.5(of)-252.7(nuclear)]TJ
0 -1.1284 TD
[(medicine.)-335.5(Semin)-336.2(Nucl)-335.1(Med)]TJ
/F8 1 Tf
11.6129 0 TD
(47:)Tj
/F3 1 Tf
1.3357 0 TD
(135142.)Tj
12.3083 69.7752 TD
[(66.)-500.5(Graber)-576.6(E,)-569.3(Regelmann)-578.8(MO,)-568.4(Annunziato)-571.4(R,)-572.2(Machac)-578.1(J,)]TJ
1.7505 -1.1223 TD
[(Rapaport)-455.2(R)-450.2(2015)-445.8(The)-451.8(role)-445.7(of)-453.9(\(1\)\(2\)\(3\)I)-450.7(imaging)-448.9(in)-445(the)]TJ
0 -1.1284 TD
[(evaluation)-451.5(of)-447.8(infants)-450.8(with)-446.2(mild)-450.3(congenital)-451.5(hypothyroid-)]TJ
0 -1.1223 TD
[(ism.)-334.1(Horm)-339.5(Res)-331.8(Paediatr)]TJ
/F8 1 Tf
10.1552 0 TD
(83:)Tj
/F3 1 Tf
1.3357 0 TD
(94101.)Tj
-13.2414 -1.1283 TD
[(67.)-500.5(Goldis)-518.8(M,)-517.9(Waldman)-525.1(L,)-514.4(Marginean)-521.2(O,)-520.2(Rosenberg)-516.1(HK,)]TJ
1.7505 -1.1223 TD
[(Rapaport)-345.5(R)-346.5(2016)-336(Thyroid)-346.2(imaging)-345.2(in)-341.3(infants.)-341(Endocrinol)]TJ
0 -1.1284 TD
[(Metab)-337.2(Clin)-333.6(North)-333.4(Am)]TJ
/F8 1 Tf
9.4599 0 TD
(45:)Tj
/F3 1 Tf
1.3357 0 TD
(255266.)Tj
-12.5461 -1.1223 TD
[(68.)-500.5(Fugazzola)-355.9(L,)-355.9(Persani)-354.7(L,)-349.8(Vannucchi)-356.5(G,)-355.5(Carletto)-356.5(M,)-353.2(Man-)]TJ
1.7505 -1.1284 TD
[(navola)-313.7(D,)-312.9(Vigone)-311(MC,)-315.5(Cortinovis)-310.9(F,)-308.1(Beccaria)-315.4(L,)-313.2(Longari)]TJ
0 -1.1223 TD
[(V,)-416.5(Weber)-412.3(G,)-410.4(Beck-Peccoz)-421.1(P)-411.7(2007)-409.2(Thyroid)-413.3(scintigraphy)]TJ
9.2951 0 0 9.2951 333.9779 620.5605 Tm
[(and)-285.2(perchlorate)-284.2(test)-277.2(after)-281.6(recombinant)-283.3(human)-285.1(TSH:)-280.8(a)-278.8(new)]TJ
T*
[(tool)-377.6(for)-377.1(the)-376.1(differential)-378.9(diagnosis)-380.7(of)-374.7(congenital)-378.3(hypothy-)]TJ
0 -1.1284 TD
[(roidism)-287.5(during)-289.3(infancy.)-291.8(Eur)-285.2(J)-285.9(Nucl)-286.4(Med)-290.6(Mol)-285.8(Imaging)]TJ
/F8 1 Tf
22.1402 0 TD
(34:)Tj
/F3 1 Tf
-22.1402 -1.1284 TD
(14981503.)Tj
-1.7505 -1.1223 TD
[(69.)-500.5(De)-451.3(Silva)-451.9(A,)-447(Jong)-451(I,)-447.8(McLean)-453.8(G,)-447(Bergman)-449.2(P,)-454.5(Rodda)-448.9(C,)]TJ
1.7505 -1.1284 TD
[(Brown)-308.3(J,)-310.4(Nandurkar)-308.7(D)-306.7(2014)-305.5(The)-305.4(role)-311.5(of)-307.6(scintigraphy)-308.7(and)]TJ
0 -1.1223 TD
[(ultrasound)-323.1(in)-323(the)-321.2(imaging)-320.8(of)-325.9(neonatal)-323.7(hypothyroidism:)-318.1(5-)]TJ
0 -1.1284 TD
[(year)-645.6(retrospective)-642.9(review)-646.9(of)-643(single-centre)-642.9(experience.)]TJ
0 -1.1223 TD
[(J)-334.7(Med)-333.3(Imaging)-335.9(Radiat)-336.2(Oncol)]TJ
/F8 1 Tf
12.3022 0 TD
(58:)Tj
/F3 1 Tf
1.3357 0 TD
(422430.)Tj
-15.3884 -1.1284 TD
[(70.)-500.5(Wasniewska)-249.4(M,)-243.4(De)-243.9(Luca)-242.6(F,)-247.1(Cassio)-245.4(A,)-239.7(Oggiaro)-246.4(N,)-245.8(Gianino)]TJ
1.7505 -1.1223 TD
[(P,)-448.4(Delvecchio)-451.8(M,)-450.8(Aiazzi)-447(R,)-450.2(Stoppioni)-447.7(V,)-447(Lombardo)-448.3(F,)]TJ
0 -1.1284 TD
[(Messina)-390.6(MF,)-380.7(Valenzise)-383.6(M,)-383.7(Arrigo)-384.7(T)-386.3(2003)-378.7(In)-380.8(congenital)]TJ
0 -1.1223 TD
[(hypothyroidism)-434.4(bone)-437.8(maturation)-437(at)-430.9(birth)-434.9(may)-431.2(be)-437.5(a)-431.3(pre-)]TJ
0 -1.1284 TD
[(dictive)-251.7(factor)-257.3(of)-246.6(psychomotor)-250.2(development)-256.6(during)-246.6(the)-254.1(rst)]TJ
0 -1.1223 TD
[(Year)-580.1(of)-582(life)-579.3(irrespective)-581.7(of)-575.9(other)-580(variables)-581.4(related)-582(to)]TJ
0 -1.1284 TD
[(treatment.)-337.4(Eur)-334(J)-334.7(Endocrinol)]TJ
/F8 1 Tf
11.68 0 TD
(149:)Tj
/F3 1 Tf
1.8298 0 TD
(16.)Tj
-15.2603 -1.1223 TD
[(71.)-500.5(Le)]TJ
2.4214 .0427 TD
()Tj
.3721 -.0427 TD
[(ge)19.9(r)-258.6(J)0(,)-249.4(E)0(c)18(o)0(s)18.9(s)12.9(e)-260.5(E)0(,)-246.1(R)13.4(ou)18(ss)19.8(ey)-248.5(M)12.8(,)-256.2(La)18(no)18(e)]TJ
13.5464 .0183 TD
()Tj
.6465 -.0183 TD
-.0185 Tc
[(J)-5.6(L)-18.5(,)-264.6(L)-18.5(ar)-18.5(ro)-18.5(qu)-18.5(e)-267(B)-273.5(2)-18.5(0)-.5(1)-18.5(1)]TJ
-15.2359 -1.1284 TD
0 Tc
[(Su)15.1(bt)24.7(le)-357.7(he)19.9(al)20.5(th)-353.5(im)19(pa)13.8(i)12.6(r)0(m)22.2(e)0(n)13.8(t)-359.4(an)13.8(d)-360(s)0(o)18.9(c)0(i)20.5(o)0(e)19.9(d)0(u)18(c)0(a)15.7(t)12.6(io)18.6(na)19.9(l)-365.5(a)0(t)20.5(t)0(a)20.5(i)0(n)18.6(m)0(e)14.2(n)0(t)]TJ
0 -1.1223 TD
[(in)-518.1(yo)18(un)24.1(g)-530.8(a)14(du)18(l)12.6(t)-530.2(pa)19.9(t)12.6(i)0(e)14.4(n)0(t)24.7(s)-529.9(wi)17(t)12.6(h)-524.7(co)19.9(ng)18(en)19.9(it)19.2(al)-516.3(hy)18(po)18(t)12.6(h)0(y)18(r)0(o)21.8(i)0(d)18.6(i)12.6(sm)]TJ
0 -1.1284 TD
[(di)18.6(ag)19.9(no)18(se)20.8(d)-238(b)0(y)-226(n)0(e)19.9(o)0(n)18(a)14(ta)14.4(l)-231.3(s)0(c)14.7(r)0(e)17.6(e)14(ni)18.6(ng)18(:)-237.4(a)-236.1(l)12.6(o)0(n)18(g)0(i)18.6(t)12.6(ud)18(i)12.6(n)0(a)19.9(l)-237.4(po)18(pu)24.1(la)14.4(t)12.6(i)0(o)18.6(n)0(-)]TJ
0 -1.1223 TD
[(based)-471.8(cohort)-464.3(study.)-462.9(J)-468.9(Clin)-467.8(Endocrinol)-460.1(Metab)]TJ
/F8 1 Tf
19.6517 0 TD
(96:)Tj
/F3 1 Tf
1.3296 0 TD
(1771)Tj
-20.9814 -1.1284 TD
(1782.)Tj
-1.7505 -1.1223 TD
[(72.)-500.5(Lichtenberger-Geslin)-299.6(L,)-294.9(Dos)-287.8(Santos)-293.2(S,)-295.9(Hassani)-289.2(Y,)-294.6(Ecosse)]TJ
1.7505 -1.1284 TD
[(E,)-368.1(Van)-360(Den)-366.1(Abbeele)-368.4(T,)-362(Le)]TJ
10.8993 .0427 TD
()Tj
.3843 -.0427 TD
[(ger)-366.8(J)-359.1(2013)-366.5(Factors)-366.9(associated)]TJ
-11.2836 -1.1223 TD
[(with)-409.7(hearing)-407.6(impairment)-406.1(in)-408.4(patients)-409.5(with)-403.5(congenital)-408.8(hy-)]TJ
0 -1.1284 TD
[(pothyroidism)-312.1(treated)-313.7(since)-312.6(the)-309(neonatal)-311.5(period:)-311.4(a)-309.3(national)]TJ
0 -1.1223 TD
[(population-based)-618.5(study.)-615.4(J)-615.3(Clin)-614.1(Endocrinol)-618.7(Metab)]TJ
/F8 1 Tf
22.1402 0 TD
(98:)Tj
/F3 1 Tf
-22.1402 -1.1284 TD
(36443652.)Tj
-1.7505 -1.1223 TD
[(73.)-500.5(Salerno)-300.7(M,)-292.2(Militerni)-297(R,)-297.8(Bravaccio)-299.1(C,)-297.8(Micillo)-294.9(M,)-298.3(Capalbo)]TJ
1.7505 -1.1284 TD
[(D,)-501.9(Di)-501.4(MS,)-496.6(Tenore)-507.5(A)-495.7(2002)-500.7(Effect)-503.2(of)-502.7(different)-497.4(starting)]TJ
0 -1.1223 TD
[(doses)-503.3(of)-496.6(levothyroxine)-498.8(on)-494.3(growth)-498.2(and)-498.7(intellectual)-497(out-)]TJ
0 -1.1284 TD
[(come)-380.6(at)-376(four)-371.2(years)-376.5(of)-374.7(age)-380.9(in)-371.8(congenital)-378.3(hypothyroidism.)]TJ
0 -1.1223 TD
(Thyroid)Tj
/F8 1 Tf
3.562 0 TD
(12:)Tj
/F3 1 Tf
1.3357 0 TD
(4552.)Tj
-6.6482 -1.1284 TD
[(74.)-500.5(Bamforth)-355.3(JS,)-350(Hughes)-353.4(IA,)-345.8(Lazarus)-358.5(JH,)-348.7(Weaver)-355.6(CM,)-346(Har-)]TJ
1.7505 -1.1223 TD
[(per)-385.1(PS)-378.1(1989)-378.7(Congenital)-385(hypothyroidism,)-385.7(spiky)-377.4(hair,)-384.8(and)]TJ
0 -1.1284 TD
[(cleft)-339.7(palate.)-335.7(J)-334.7(Med)-333.3(Genet)]TJ
/F8 1 Tf
10.7285 0 TD
(26:)Tj
/F3 1 Tf
1.3357 0 TD
(4951.)Tj
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2.2506 -1.1223 TD
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0 -1.1223 TD
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0 -1.1284 TD
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[(135.)-500.6(Korzeniewski)-505.7(SJ,)-496.4(Grigorescu)-496.5(V,)-495.8(Kleyn)-500(M,)-499.6(Young)-496.3(WI,)]TJ
2.2506 -1.1223 TD
[(Birbeck)-241.6(G,)-239.7(Todem)-238.2(D,)-233.6(Romero)-243.5(R,)-236.8(Paneth)-237.3(N)-239.6(2013)-232.4(Transient)]TJ
0 -1.1284 TD
[(hypothyroidism)-349(at)-351.6(3-year)-349.4(follow-up)-347.9(among)-352.2(cases)-347(of)-350.3(con-)]TJ
0 -1.1223 TD
[(genital)-495.6(hypothyroidism)-489.3(detected)-492.6(by)-488.2(newborn)-491(screening.)]TJ
0 -1.1284 TD
[(J)-334.7(Pediatr)]TJ
/F8 1 Tf
3.8974 0 TD
(162:)Tj
/F3 1 Tf
1.8359 0 TD
(177182.)Tj
-7.9839 -1.1223 TD
[(136.)-500.6(Ford)-365.6(GA,)-369.5(Denniston)-364.9(S,)-369.1(Sesser)-366.5(D,)-367.7(Skeels)-364.5(MR,)-370.4(LaFranchi)]TJ
2.2506 -1.1284 TD
[(SH)-517.1(2016)-519(Transient)-518.1(versus)-518(permanent)-521.5(congenital)-518.6(hypo-)]TJ
0 -1.1223 TD
[(thyroidism)-336.2(after)-342.6(the)-333.4(age)-338.2(of)-332(3)-335.6(years)-339.9(in)-335.2(infants)-334.9(detected)-340.1(on)]TJ
0 -1.1284 TD
[(the)-327.3(rst)-321.5(versus)-328.9(second)-325.6(newborn)-326.3(screening)-325.8(test)-326(in)-323(Oregon,)]TJ
0 -1.1223 TD
[(USA.)-335.9(Horm)-333.4(Res)-337.9(Paediatr)]TJ
/F8 1 Tf
10.6981 0 TD
(86:)Tj
/F3 1 Tf
1.3357 0 TD
(169177.)Tj
-14.2844 -1.1284 TD
[(137.)-500.6(Kang)-347.9(MJ,)-340.3(Chung)-341(HR,)-348.3(Oh)-343.4(YJ,)-342.6(Shim)-337.9(YS,)-346.4(Yang)-341.8(S,)-344.7(Hwang)]TJ
2.2506 -1.1223 TD
[(IT)-358.2(2017)-348.2(Three-year)-362.6(follow-up)-354(of)-356.4(children)-352.3(with)-354.8(abnormal)]TJ
0 -1.1284 TD
[(newborn)-320.2(screening)-313.6(results)-315.7(for)-316.1(congenital)-317.3(hypothyroidism.)]TJ
0 -1.1223 TD
[(Pediatr)-336.8(Neonatol)]TJ
/F8 1 Tf
7.191 0 TD
(58:)Tj
/F3 1 Tf
1.3296 0 TD
(442448.)Tj
-10.7712 -1.1284 TD
[(138.)-500.6(Park)-357.7(IS,)-353.2(Yoon)-355.9(JS,)-350(So)-356.9(CH,)-354.4(Lee)-358.4(HS,)-352.5(Hwang)-355.7(JS)-356(2017)-354.3(Pre-)]TJ
2.2506 -1.1223 TD
[(dictors)-310.5(of)-307.6(transient)-314.4(congenital)-311.2(hypothyroidism)-312.4(in)-304.7(children)]TJ
0 -1.1284 TD
[(with)-257.2(eutopic)-258.3(thyroid)-252.3(gland.)-254.5(Ann)-252.1(Pediatr)-257.5(Endocrinol)-258.8(Metab)]TJ
/F8 1 Tf
0 -1.1223 TD
(22:)Tj
/F3 1 Tf
1.3357 0 TD
(115118.)Tj
-3.5863 -1.1284 TD
[(139.)-500.6(Zdraveska)-1102.9(N,)-1099.7(Zdravkovska)-1105.1(M,)-1097.3(Anastasovska)-1104.5(V,)]TJ
2.2506 -1.1223 TD
[(Sukarova-Angelovska)-381(E,)-380.3(Kocova)-376.8(M)-377.5(2018)-372.6(Diagnostic)-380.9(re-)]TJ
0 -1.1284 TD
[(evaluation)-488.1(of)-478.3(congenital)-482(hypothyroidism)-483.2(in)-481.5(Macedonia:)]TJ
0 -1.1223 TD
[(predictors)-640.7(for)-633.3(transient)-637.7(or)-636.9(permanent)-637.4(hypothyroidism.)]TJ
0 -1.1284 TD
[(Endocr)-338.6(Connect)]TJ
/F8 1 Tf
6.9104 0 TD
(7:)Tj
/F3 1 Tf
.8295 0 TD
(278285.)Tj
-9.9905 -1.1223 TD
[(140.)-500.6(Fu)-295.9(C,)-291.7(Luo)-295.1(S,)-295.9(Li)-294.4(Y,)-294.6(Li)-294.4(Q,)-294.6(Hu)-294.6(X,)-294.6(Li)-294.4(M,)-298.3(Zhang)-293.5(Y,)-294.6(Su)-295.9(J,)-292.1(Hu)]TJ
2.2506 -1.1284 TD
[(X,)-264.1(Chen)-265.7(Y,)-264.1(Wang)-259.2(J,)-267.7(Xie)-261.8(B,)-261.2(Luo)-264.6(J,)-261.6(Fan)-263.7(X,)-264.1(Chen)-265.7(S,)-259.3(Shen)-263.8(Y)]TJ
0 -1.1223 TD
[(2017)-268.9(The)-262.7(incidence)-273.2(of)-264.9(congenital)-268.5(hypothyroidism)-269.7(\(CH\))-267.7(in)]TJ
0 -1.1284 TD
[(Guangxi,)-597.9(China)-600.8(and)-596.3(the)-595.7(predictors)-598(of)-600.3(permanent)-594.7(and)]TJ
0 -1.1223 TD
[(transient)-338.8(CH.)-336.1(Endocr)-332.5(Connect)]TJ
/F8 1 Tf
12.6681 0 TD
(6:)Tj
/F3 1 Tf
.8356 0 TD
(926934.)Tj
-15.7543 -1.1284 TD
[(141.)-500.6(Razavi)-414.2(Z,)-416.9(Mohammadi)-410.1(L)-416.8(2017)-409.2(Permanent)-414.6(and)-413.3(transient)]TJ
2.2506 -1.1223 TD
[(congenital)-317.3(hypothyroidism)-312.4(in)-304.7(Hamadan)-313.7(West)-312.6(Province)-313.1(of)]TJ
0 -1.1284 TD
[(Iran.)-338.9(Int)-331.5(J)-334.7(Endocrinol)-332(Metab)]TJ
/F8 1 Tf
12.0521 0 TD
(14:)Tj
/F3 1 Tf
1.3357 0 TD
(e38256.)Tj
-15.6384 -1.1223 TD
[(142.)-500.6(Rabbiosi)-429(S,)-424(Vigone)-426.9(MC,)-425.3(Cortinovis)-432.9(F,)-424(Zamproni)-423.3(I,)-429.5(Fu-)]TJ
2.2506 -1.1284 TD
[(gazzola)-310(L,)-307.1(Persani)-306(L,)-307.1(Corbetta)-308.3(C,)-303.9(Chiumello)-307(G,)-306.8(Weber)-308.6(G)]TJ
T*
[(2013)-616.6(Congenital)-622.9(hypothyroidism)-617.3(with)-623.1(eutopic)-618.2(thyroid)]TJ
0 -1.1223 TD
[(gland:)-528.5(analysis)-525.1(of)-521(clinical)-529.9(and)-523.1(biochemical)-528.6(features)-523.2(at)]TJ
0 -1.1284 TD
[(diagnosis)-246.6(and)-248.6(after)-245(re-evaluation.)-253.5(J)-243.2(Clin)-248.2(Endocrinol)-246.6(Metab)]TJ
/F8 1 Tf
0 -1.1223 TD
(98:)Tj
/F3 1 Tf
1.3357 0 TD
(13951402.)Tj
-3.5863 -1.1284 TD
[(143.)-500.6(O)16.6(l)18.7(i)18.7(v)18.2(i)12.6(e)20.1(r)15.8(i)-566.8(A)16.6(,)-567.3(F)15.3(a)20.1(z)14(z)20.1(i)12.6(n)18.2(i)-566.8(C)19.5(,)-573.4(M)18.9(e)20.1(d)18.2(d)18.2(a)-571.6(E)]TJ
16.6875 0 TD
-.018 Tc
[(2015)-591.5(Multiple)-589.6(factors)]TJ
-14.4369 -1.1223 TD
-.0182 Tc
[(inuencing)-359.9(the)-358(i).5(ncidence)-358(of)-356.1(congeni)-5.6(tal)-359.3(hypothyroidism)-359.5(de-)]TJ
0 -1.1284 TD
-.0178 Tc
[(tect)-5.2(ed)-280.2(by)-280.2(neonatal)-279.6(s)1.2(creening.)-280.1(Horm)-279.8(Res)-279.3(P)-2.5(aediatr)]TJ
/F8 1 Tf
19.2553 0 TD
-.0182 Tc
(83:)Tj
/F3 1 Tf
1.5614 0 TD
(8693.)Tj
-23.0673 -1.1223 TD
0 Tc
[(144.)-500.6(Zung)-264.7(A,)-264.1(Tenenbaum-Rakover)-266.2(Y,)-264.1(Barkan)-266.5(S,)-265.4(Hanukoglu)-262.7(A,)]TJ
2.2506 -1.1284 TD
[(Hershkovitz)-463.2(E,)-465.6(Pinhas-Hamiel)-463.5(O,)-459.2(Bistritzer)-467.4(T,)-459.5(Zadik)-463.7(Z)]TJ
0 -1.1223 TD
[(2010)-390.9(Neonatal)-398.5(hyperthyrotropinemia:)-397.5(population)-394.3(charac-)]TJ
0 -1.1284 TD
[(teristics,)-435(diagnosis,)-429.6(management)-431.6(and)-431.6(outcome)-429.3(after)-427.9(ces-)]TJ
0 -1.1223 TD
[(sation)-338.5(of)-332(therapy.)-334.5(Clin)-333.6(Endocrinol)-338.1(\(Oxf)-86.1(\))]TJ
/F8 1 Tf
16.9803 0 TD
(72:)Tj
/F3 1 Tf
1.3357 0 TD
(264271.)Tj
-20.5666 -1.1284 TD
[(145.)-500.6(Unuvar)-429.8(T,)-429.1(Demir)-428.7(K,)-428.7(Abaci)-424.9(A,)-428.7(Buyukgebiz)-428.8(A,)-428.7(Bober)-426.8(E)]TJ
2.2506 -1.1223 TD
[(2013)-293.3(The)-293.2(role)-293.2(of)-289.3(initial)-295.1(clinical)-292(and)-291.3(laboratory)-293.9(ndings)-295.2(in)]TJ
0 -1.1284 TD
[(infants)-395.9(with)-391.4(hyperthyrotropinemia)-397.9(to)-390.1(predict)-394.9(transient)-393.7(or)]TJ
0 -1.1223 TD
[(permanent)-289.7(hypothyroidism.)-294.2(J)-285.9(Clin)-290.9(Res)-289.1(Pediatr)-288(Endocrinol)]TJ
/F8 1 Tf
0 -1.1284 TD
(5:)Tj
/F3 1 Tf
.8356 0 TD
(170173.)Tj
23.9273 69.7752 TD
[(146.)-500.6(Messina)-250.3(MF,)-252.6(Aversa)-250.2(T,)-252.2(Salzano)-253.8(G,)-245.8(Zirilli)-252.4(G,)-251.9(Sferlazzas)-254.2(C,)]TJ
2.2506 -1.1223 TD
[(De)-439.1(Luca)-437.8(F,)-442.3(Lombardo)-436.1(F)-442.2(2015)-433.6(Early)-441.6(discrimination)-441.6(be-)]TJ
0 -1.1284 TD
[(tween)-278.5(transient)-283.9(and)-285.2(permanent)-283.6(congenital)-280.7(hypothyroidism)]TJ
0 -1.1223 TD
[(in)-463.2(children)-468.2(with)-464.5(eutopic)-471.8(gland.)-468(Horm)-461.5(Res)-472.1(Paediatr)]TJ
/F8 1 Tf
22.1402 0 TD
(84:)Tj
/F3 1 Tf
-22.1402 -1.1283 TD
(159164.)Tj
-2.2506 -1.1223 TD
[(147.)-500.6(Eugster)-495.9(EA,)-504(LeMay)-498.2(D,)-501.9(Zerin)-496.5(JM,)-498.9(Pescovitz)-502.7(OH)-497.5(2004)]TJ
2.2506 -1.1284 TD
[(Denitive)-341.8(diagnosis)-338.1(in)-335.2(children)-340.1(with)-342.6(congenital)-341.7(hypothy-)]TJ
0 -1.1223 TD
[(roidism.)-330.3(J)-334.7(Pediatr)]TJ
/F8 1 Tf
7.5387 0 TD
(144:)Tj
/F3 1 Tf
1.8359 0 TD
(643647.)Tj
-11.6251 -1.1284 TD
[(148.)-500.6(Saba)-615.7(C,)-621(Guilmin-Crepon)-618.9(S,)-619.1(Zenaty)-614.4(D,)-617.8(Martinerie)-626.2(L,)]TJ
2.2506 -1.1223 TD
[(Paulsen)-291.4(A,)-288.5(Simon)-289.3(D,)-288.5(Storey)-290.3(C,)-291.7(Dos)-287.8(Santos)-293.2(S,)-289.8(Haignere)-291.6(J,)]TJ
9.2951 0 0 9.2951 331.7668 620.5605 Tm
[(Mohamed)-362(D,)-355.6(Carel)-363.3(JC,)-358(Le)]TJ
10.6188 .0427 TD
()Tj
.3843 -.0427 TD
[(ger)-360.7(J)-359.1(2018)-360.4(Early)-362.3(determinants)]TJ
-11.003 -1.1223 TD
[(of)-356.4(thyroid)-362(function)-360.3(outcomes)-361.4(in)-359.6(children)-364.5(with)-360.9(congenital)]TJ
0 -1.1284 TD
[(hypothyroidism)-403.9(and)-413.3(a)-406.9(normally)-408.7(located)-408.9(thyroid)-410.8(gland:)-406.5(a)]TJ
T*
[(regional)-334(cohort)-336.2(study.)-334.8(Thyroid)]TJ
/F8 1 Tf
12.8328 0 TD
(28:)Tj
/F3 1 Tf
1.3296 0 TD
(959967.)Tj
-16.413 -1.1223 TD
[(149.)-500.6(Oron)-901.1(T,)-904.8(Lazar)-908(L,)-904.8(Ben-Yishai)-907(S,)-905.8(Tenenbaum)-905.9(A,)]TJ
2.2506 -1.1284 TD
[(Yackobovitch-Gavan)-473.2(M,)-463(Meyerovitch)-472.1(J,)-469(Phillip)-465.1(M,)-463(Le-)]TJ
0 -1.1223 TD
[(benthal)-380.3(Y)-373.8(2018)-378.7(Permanent)-378(vs)-377.6(transient)-381.5(congenital)-384.4(hypo-)]TJ
0 -1.1284 TD
[(thyroidism:)-591.9(assessment)-601.2(of)-588.1(predictive)-600.2(variables.)-593.7(J)-597(Clin)]TJ
0 -1.1223 TD
[(Endocrinol)-332(Metab)]TJ
/F8 1 Tf
7.685 0 TD
(103:)Tj
/F3 1 Tf
1.8359 0 TD
(44284436.)Tj
-11.7715 -1.1284 TD
[(150.)-500.6(Valizadeh)-500.4(M,)-499.6(Moezzi)-506.2(F,)-497.1(Khavassi)-502.9(Z,)-502.2(Movahedinia)-500.3(M,)]TJ
2.2506 -1.1223 TD
[(Mazloomzadeh)-496.8(S,)-491.1(Mehran)-498.8(L)-496.1(2017)-488.5(Inuence)-500.8(of)-490.5(topical)]TJ
0 -1.1284 TD
[(iodine-containing)-386.6(antiseptics)-388.3(used)-382(during)-380.8(delivery)-388.9(on)-384.5(re-)]TJ
0 -1.1223 TD
[(call)-276.2(rate)-279.1(of)-271(congenital)-280.7(hypothyroidism)-275.8(screening)-283.1(program.)]TJ
0 -1.1284 TD
[(J)-328.6(Pediatr)-336.8(Endocrinol)-338.1(Metab)]TJ
/F8 1 Tf
11.5824 0 TD
(30:)Tj
/F3 1 Tf
1.3296 0 TD
(973978.)Tj
-15.1627 -1.1223 TD
[(151.)-500.6(Chanoine)-422.4(JP,)-417.1(Boulvain)-423.8(M,)-420.3(Bourdoux)-423(P,)-417.9(Pardou)-418.9(A,)-422.6(Van)]TJ
2.2506 -1.1284 TD
[(Thi)-434.8(HV,)-436.6(Ermans)-441(AM,)-440.3(Delange)-441.6(F)-436.1(1988)-433.6(Increased)-442.7(recall)]TJ
0 -1.1223 TD
[(rate)-358.4(at)-363.8(screening)-362.4(for)-358.8(congenital)-360(hypothyroidism)-361.2(in)-359.6(breast)]TJ
0 -1.1284 TD
[(fed)-379(infants)-377.6(born)-375(to)-377.9(iodine)-376(overloaded)-381.8(mothers.)-377.8(Arch)-380.7(Dis)]TJ
0 -1.1223 TD
(Child)Tj
/F8 1 Tf
2.5617 0 TD
(63:)Tj
/F3 1 Tf
1.3296 0 TD
(12071210.)Tj
-6.1419 -1.1284 TD
[(152.)-500.6(T)-14.2(h)-18.4(a)-22.6(k)-18.4(e)-16.5(r)-368.4(V)-20(V)-20(,)-366(G)-20(a)-22.6(l)-17.9(l)-17.9(e)-16.5(r)-368.4(M)-23.8(F)-15.2(,)-372.1(M)-17.7(a)-16.5(r)-20.8(s)-17.6(h)-18.4(a)-16.5(l)-17.9(l)-371.6(A)-20(C)-17.1(,)-372.1(A)-13.9(l)-24(m)-18(o)]TJ
21.1582 0 TD
.0187 Tc
[(dovar)-349.7(M)1(C,)]TJ
-18.9076 -1.1223 TD
.0177 Tc
[(Hs)-6(u)-238.6(H)-2.3(W,)-244.6(Addis)-243.8(C).6(J,)-244.6(Feldman)-238.6(HA,)-238.5(Brown)-238.6(R)-5.5(S,)-244.6(Levine)-242.8(BS)]TJ
0 -1.1284 TD
.0182 Tc
[(201)5.9(7)-439.4(H)-1.8(y)5.9(pothyroidism)-432.8(in)-439.4(infants)-432.4(w)-1.8(ith)-433.3(congenital)-438.8(h)-.2(eart)]TJ
0 -1.1223 TD
[(disease)-278.8(e)1.8(xposed)-280.7(to)-274.6(excess)-279.8(iodine.)-274.5(J)-279.8(Endo)6(cr)-276.9(Soc)]TJ
/F8 1 Tf
20.0299 0 TD
.0184 Tc
(1:)Tj
/F3 1 Tf
.8722 0 TD
[(10)6.1(67)]TJ
-20.9021 -1.1284 TD
[(107)6.1(8.)]TJ
-2.2506 -1.1223 TD
0 Tc
[(153.)-500.6(Connelly)-265.2(KJ,)-269.4(Boston)-266.5(BA,)-262.9(Pearce)-273(EN,)-266.1(Sesser)-268.9(D,)-264.1(Snyder)-266.5(D,)]TJ
2.2506 -1.1284 TD
[(Braverman)-443.8(LE,)-443.3(Pino)-442(S,)-448.4(LaFranchi)-441.3(SH)-443.9(2012)-445.8(Congenital)]TJ
0 -1.1223 TD
[(hypothyroidism)-251.4(caused)-256.6(by)-250.4(excess)-255.7(prenatal)-258.9(maternal)-258.5(iodine)]TJ
0 -1.1284 TD
[(ingestion.)-332.3(J)-334.7(Pediatr)]TJ
/F8 1 Tf
8.1547 0 TD
(161:)Tj
/F3 1 Tf
1.8298 0 TD
(760762.)Tj
-12.2351 -1.1223 TD
[(154.)-500.6(Le)]TJ
2.9276 .0366 TD
()Tj
.3842 -.0366 TD
[(ger)-348.5(J,)-347(dos)-353.3(Santos)-348.1(S,)-350.8(Larroque)-351.6(B,)-346.6(Ecosse)-351(E)-349.7(2015)-348.2(Preg-)]TJ
-1.0613 -1.1284 TD
[(nancy)-271.4(outcomes)-270(and)-273(relationship)-271.6(to)-274.2(treatment)-270.3(adequacy)-274.2(in)]TJ
0 -1.1223 TD
[(women)-555(treated)-563.7(early)-559.8(for)-560.1(congenital)-561.3(hypothyroidism:)-562(a)]TJ
0 -1.1284 TD
[(longitudinal)-545.9(population-based)-545.3(study.)-548.3(J)-548.2(Clin)-540.9(Endocrinol)]TJ
0 -1.1223 TD
(Metab)Tj
/F8 1 Tf
2.891 0 TD
(100:)Tj
/F3 1 Tf
1.8359 0 TD
(860869.)Tj
-6.9775 -1.1284 TD
[(155.)-500.6(Alexander)-255.1(EK,)-253.9(Pearce)-254.7(EN,)-253.9(Brent)-249.3(GA,)-253.6(Brown)-253.4(RS,)-258.1(Chen)-247.4(H,)]TJ
2.2506 -1.1223 TD
[(Dosiou)-238.9(C,)-236.8(Grobman)-240.5(WA,)-238.1(Laurberg)-241.8(P,)-234.9(Lazarus)-242.6(JH,)-238.9(Mandel)]TJ
0 -1.1284 TD
[(SJ,)-398.8(Peeters)-407.7(RP,)-404.5(Sullivan)-403(S)-399.5(2017)-403.1(2017)-403.1(Guidelines)-405.3(of)-405.2(the)]TJ
T*
[(American)-657.1(Thyroid)-657.3(Association)-660.7(for)-657.7(the)-656.7(diagnosis)-655.2(and)]TJ
0 -1.1223 TD
[(management)-321.8(of)-319.8(thyroid)-325.4(disease)-322.3(during)-319.8(pregnancy)-327.3(and)-321.8(the)]TJ
0 -1.1284 TD
[(postpartum.)-335(Thyroid)]TJ
/F8 1 Tf
8.6548 0 TD
(27:)Tj
/F3 1 Tf
1.3296 0 TD
(315389.)Tj
-12.2351 -1.1223 TD
[(156.)-500.6(Le)]TJ
2.9276 .0427 TD
()Tj
.3842 -.0427 TD
[(ger)-336.3(J,)-340.9(Forhan)-339.7(A,)-337.2(Dos)-342.7(Santos)-335.9(S,)-338.6(Larroque)-339.4(B,)-340.5(Ecosse)-344.9(E,)]TJ
-1.0613 -1.1284 TD
[(Charles)-301.7(MA,)-306.2(Heude)-303.5(B)-303.8(2018)-305.5(Developmental)-304.8(milestones)-310.9(at)]TJ
0 -1.1223 TD
[(one)-523.1(year)-529.7(for)-523.5(the)-528.6(offspring)-525.2(of)-527.1(mothers)-530.2(with)-525.5(congenital)]TJ
0 -1.1284 TD
[(hypothyroidism:)-635.2(a)-632.6(population-based)-636.8(study.)-633.7(Eur)-632.9(J)-633.6(En-)]TJ
0 -1.1223 TD
(docrinol)Tj
/F8 1 Tf
3.6778 0 TD
(178:)Tj
/F3 1 Tf
1.8298 0 TD
(471480.)Tj
-7.7582 -1.1284 TD
[(157.)-500.6(Korevaar)-367.7(TIM,)-369.9(Muetzel)-371.6(R,)-364.9(Medici)-367.3(M,)-371.5(Chaker)-364(L,)-368.1(Jaddoe)]TJ
2.2506 -1.1223 TD
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6.7458 .0366 TD
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2.2506 -1.1284 TD
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9.2951 0 0 9.2951 333.9779 170.759 Tm
[(docrinol)-335.9(Metab)]TJ
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40.9535 0 TD
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2.2506 -1.1284 TD
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2.2506 -1.1223 TD
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10.082 .2318 TD
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14.8882 0 TD
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15.8031 .0427 TD
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[(Schmitt)-475.6(A,)-471.4(Bole-Feysot)-475.4(C,)-474.6(Nitschke)-472.7(P,)-472.8(Leger)-476.9(J,)-469(Jabot-)]TJ
0 -1.1223 TD
[(Hanin)-451.2(F,)-448.4(Tores)-453.5(F,)-448.4(Michel)-452.6(A,)-453.1(Munnich)-449.2(A,)-453.1(Besmond)-447.8(C,)]TJ
0 -1.1284 TD
[(Scharfmann)-240.8(R,)-242.9(Lanza)-240.9(F,)-241(Borgel)-237.3(D,)-239.7(Polak)-245.1(M,)-237.3(Carre)]TJ
19.8896 .0427 TD
()Tj
.6282 -.0427 TD
[(A)-239.6(2018)]TJ
-20.5178 -1.1284 TD
[(TUBB1)-556.6(mutations)-557.5(cause)-555.3(thyroid)-551.1(dysgenesis)-555.6(associated)]TJ
0 -1.1223 TD
[(with)-360.9(abnormal)-364.7(platelet)-359.1(physiology.)-359.4(EMBO)-361.8(Mol)-359(Med)]TJ
/F8 1 Tf
22.1402 0 TD
(10:)Tj
/F3 1 Tf
-22.1402 -1.1284 TD
(e9569.)Tj
-2.2506 -1.1223 TD
[(219.)-500.6(Thorwarth)-250.9(A,)-245.8(Schnittert-Hubener)-254.3(S,)-247.1(Schrumpf)-244.2(P,)-247.1(Muller)-249.5(I,)]TJ
2.2506 -1.1284 TD
[(Jyrch)-244.2(S,)-247.1(Dame)-241.9(C,)-249(Biebermann)-245.8(H,)-245.8(Kleinau)-247.7(G,)-239.7(Katchanov)-246.7(J,)]TJ
0 -1.1223 TD
[(Schuelke)-668.7(M,)-664.3(Ebert)-667.3(G,)-672.7(Steininger)-666(A,)-666.6(Bonnemann)-666.7(C,)]TJ
0 -1.1284 TD
[(Brockmann)-327.5(K,)-331.2(Christen)-327.6(HJ,)-330.4(Crock)-329.2(P,)-326.4(deZegher)-335.2(F,)-326.4(Griese)]TJ
0 -1.1223 TD
[(M,)-280(Hewitt)-281(J,)-279.9(Ivarsson)-282.7(S,)-283.7(Hubner)-277.3(C,)-285.6(Kapelari)-278.8(K,)-282.4(Plecko)-280(B,)]TJ
0 -1.1284 TD
[(Rating)-399.1(D,)-404.3(Stoeva)-402(I,)-399(Ropers)-401.6(HH,)-400(Gruters)-406.4(A,)-398.2(Ullmann)-401.7(R,)]TJ
0 -1.1223 TD
[(Krude)-509(H)-507.9(2014)-506.8(Comprehensive)-507.7(genotyping)-510.8(and)-504.8(clinical)]TJ
0 -1.1284 TD
[(characterisation)-425.5(reveal)-430(27)-421.1(novel)-419.1(NKX2-1)-422.7(mutations)-423.3(and)]TJ
0 -1.1223 TD
[(expand)-430.1(the)-437.1(phenotypic)-429.6(spectrum.)-437(J)-426.2(Med)-436.9(Genet)]TJ
/F8 1 Tf
20.1397 0 TD
(51:)Tj
/F3 1 Tf
1.3357 0 TD
(375)Tj
-21.4754 -1.1284 TD
(387.)Tj
-2.2506 -1.1223 TD
[(220.)-500.6(Zou)-404.9(M,)-402(Alzahrani)-413.1(AS,)-401.3(Al-Odaib)-412.2(A,)-404.3(Alqahtani)-406(MA,)-403.8(Ba-)]TJ
2.2506 -1.1284 TD
[(biker)-268.9(O,)-270.2(Al-Rijjal)-273.6(RA,)-269(BinEssa)-271.8(HA,)-271.9(Kattan)-272(WE,)-268.9(Al-Enezi)]TJ
0 -1.1223 TD
[(AF,)-267.1(Al)-263.6(Qarni)-264.4(A,)-270.2(Al-Faham)-265.4(MSA,)-266.5(Baitei)-268.5(EY,)-266.1(Alsagheir)-267.8(A,)]TJ
0 -1.1284 TD
[(Meyer)-370.6(BF,)-374(Shi)-368.7(Y)-373.8(2018)-372.6(Molecular)-374.2(analysis)-372.6(of)-368.6(congenital)]TJ
0 -1.1223 TD
[(hypothyroidism)-330.7(in)-335.2(Saudi)-330.5(Arabia:)-335.4(SLC26A7)-335.4(mutation)-332.6(is)-328.2(a)]TJ
0 -1.1284 TD
[(novel)-480.1(defect)-478.8(in)-481.5(thyroid)-477.9(dyshormonogenesis.)-485.4(J)-475(Clin)-479.9(En-)]TJ
0 -1.1223 TD
[(docrinol)-335.9(Metab)]TJ
/F8 1 Tf
6.575 0 TD
(103:)Tj
/F3 1 Tf
1.8298 0 TD
(18891898.)Tj
-10.6554 -1.1284 TD
[(221.)-500.6(Cangul)-338.6(H,)-337.3(Liao)-341.6(XH,)-339(Schoenmakers)-339.6(E,)-337.6(Kero)-344.1(J,)-334.8(Barone)-339.6(S,)]TJ
2.2506 -1.1223 TD
[(Srichomkwun)-359.3(P,)-350.8(Iwayama)-358.7(H,)-355.5(Serra)-358.2(EG,)-357.6(Saglam)-358.8(H,)-355.5(Eren)]TJ
0 -1.1284 TD
[(E,)-502.2(Tarim)-508.3(O,)-508(Nicholas)-509.3(AK,)-503.7(Zvetkova)-504.9(I,)-508.8(Anderson)-502.4(CA,)]TJ
0 -1.1223 TD
[(Frankl)-540.4(FEK,)-537.5(Boelaert)-544.3(K,)-538.5(Ojaniemi)-539.6(M,)-542.3(Ja)]TJ
17.6756 .0183 TD
()Tj
.3843 -.0183 TD
(a)Tj
.061 .0183 TD
()Tj
.3904 -.0183 TD
(skela)Tj
1.6773 .0183 TD
()Tj
.3843 -.0183 TD
[(inen)-534.8(J,)]TJ
-20.5727 -1.1284 TD
[(Patyra)-349.4(K,)-343.3(Lo)]TJ
4.916 .0244 TD
()Tj
.4208 -.0244 TD
[(f)-344(C)0(,)-340.5(Williams)-353.8(ED;)-344.9(UK10K)-347(Consortium,)-341.6(So-)]TJ
-5.3368 -1.1223 TD
[(leimani)-293.9(M,)-298.3(Barrett)-298.3(T,)-288.8(Maher)-297.4(ER,)-293.7(Chatterjee)-304.2(VK,)-290.2(Refetoff)]TJ
0 -1.1284 TD
[(S,)-478.9(Schoenmakers)-479.9(N)-477.4(2018)-476.3(Homozygous)-475.6(loss-of-function)]TJ
0 -1.1223 TD
[(muttaions)-441.6(in)-445(SLC26A7)-445.2(cause)-445.5(goitrous)-440.6(congenital)-445.4(hypo-)]TJ
0 -1.1284 TD
[(thyroidism.)-336.3(JCI)-336(Insight)]TJ
/F8 1 Tf
9.7588 0 TD
(3:)Tj
/F3 1 Tf
.8356 0 TD
(e99631.)Tj
-12.845 -1.1223 TD
[(222.)-500.6(Kuhnen)-445.8(P,)-442.3(Turan)-442.2(S,)-448.4(Frohler)-445.2(S,)-442.3(Guran)-441.9(T,)-447.3(Abali)-444.5(S,)-442.3(Bie-)]TJ
2.2506 -1.1284 TD
[(bermann)-243.1(H,)-239.7(Bereket)-245.8(A,)-239.7(Gruters)-241.7(A,)-239.7(Chen)-241.3(W,)-242.4(Krude)-240.6(H)-245.7(2014)]TJ
0 -1.1223 TD
[(Identication)-377.3(of)-368.6(PENDRIN)-371.4(\(SLC26A4\))-377(mutations)-374.5(in)-371.8(pa-)]TJ
0 -1.1284 TD
[(tients)-569.7(with)-574.3(congenital)-573.5(hypothyroidism)-574.6(and)-571.9()58.5(apparent)46.6()]TJ
T*
[(thyroid)-484(dysgenesis.)-488.6(J)-487.2(Clin)-486(Endocrinol)-490.6(Metab)]TJ
/F8 1 Tf
19.5236 0 TD
(99:)Tj
/F3 1 Tf
1.3357 0 TD
(E169)Tj
-20.8594 -1.1223 TD
(E176.)Tj
-2.7874 -1.1284 TD
[(222a.)-505(S)-15.2(t)-11.8(o)-18.4(u)-12.3(p)-12.3(a)-339.8(A)-13.9(,)-335.5(C)-11(h)-18.4(a)-16.5(a)-16.5(b)-12.3(a)-16.5(n)-12.3(e)-339.8(R)-11(,)-335.5(G)-20(u)-12.3(e)]TJ
14.1807 .0427 TD
()Tj
.4026 -.0427 TD
.0135 Tc
[(ri)-4.4(ouz)-326.3(M,)-322(Rayn)-4.9(au)-4.9(d-Rav)-4.9(n)1.2(i)-321.5(C)-3.6(,)]TJ
-11.8813 -1.1223 TD
.0155 Tc
[(Nitsc)5.1(h)-2.9(ke)-354.8(P,)-350.5(Bole-Feysot)-356.1(C)-1.6(,)-350.5(M)-2.2(nif)-352.9(M)3.9(,)-356.6(A)1.6(mmar)-352.9(Keskes)-349.7(L,)]TJ
0 -1.1284 TD
.0163 Tc
[(Hach)4(ich)4(a)-665.1(M)4.7(,)-660.8(Belg)4(u)4(ith)-660.9(N,)-660.8(Po)4(lak)-660.9(M)-1.4(,)-660.8(C)-.8(a)5.9(r)-4.5(re)]TJ
19.054 .0427 TD
0 Tc
()Tj
1.0613 -.0427 TD
.6787 Tc
[(A2)660.3(0)666.4(1)660.3(8)]TJ
-20.1153 -1.1223 TD
.0133 Tc
[(Thy)-5.1(r)-1.4(oi)-4.6(d)-383.3(h)-5.1(ypo)-5.1(pl)-4.6(asi)-4.6(a)-387.5(in)-389.4(con)-5.1(g)1(eni)-4.6(t)1.5(al)-388.8(hy)-5.1(po)-5.1(th)-5.1(yro)-5.1(i)1.5(d)-5.1(i)1.5(s)-4.3(m)-382.9(as)-4.2(s)-4.2(o)1(-)]TJ
0 -1.1284 TD
.0151 Tc
[(c)4.7(i)-2.8(ated)-448.6(with)-448.6(thyroid)-448.6(p)2.8(erox)]TJ
11.0274 0 TD
.0135 Tc
[(i)-4.4(d)1.2(as)-4(e)-448.3(m)1.6(u)-4.9(t)1.7(at)-4.4(io)-4.9(ns)-4(.)-444(T)-6.8(hyr)-7.3(oi)-4.4(d)]TJ
/F8 1 Tf
11.1677 0 TD
.0184 Tc
[(28)6.1(:)]TJ
/F3 1 Tf
-22.1951 -1.1223 TD
.0123 Tc
[(941)-6.1(9)-6.1(44)-6.1(.)]TJ
-2.1652 -1.1284 TD
0 Tc
[(223.)-500.6(Srichomkwun)-414.2(P,)-417.9(Takamatsu)-416.5(J,)-414.1(Nickerson)-420.8(DA,)-412.2(Bamshad)]TJ
2.2506 -1.1223 TD
[(MJ,)-370.8(Chong)-371.5(JX,)-373.1(Refetoff)-380.6(S)-369(2017)-372.6(DUOX2)-373(Gene)-376.5(mutation)]TJ
0 -1.1284 TD
[(manifesting)-381.3(as)-381.8(resistance)-383.6(to)-384(thyrotropin)-376.6(phenotype.)-381.3(Thy-)]TJ
0 -1.1223 TD
(roid)Tj
/F8 1 Tf
1.9457 0 TD
(27:)Tj
/F3 1 Tf
1.3357 0 TD
(129131.)Tj
-5.532 -1.1284 TD
[(224.)-500.6(Kizys)-371(MML,)-373(Louzada)-375.4(RA,)-372.7(Mitne-Neto)-371.2(M,)-371.5(Jara)-376.4(JR,)-370.2(Fur-)]TJ
2.2506 -1.1223 TD
[(uzawa)-515.1(GK,)-515.9(de)-516.8(Carvalho)-516.2(DP,)-517.2(Dias-da-Silva)-521.1(MR,)-510.6(Nesi-)]TJ
0 -1.1284 TD
[(Franca)-250.5(S,)-241(Dupuy)-246.3(C,)-249(Maciel)-249.5(RMB)-247.1(2017)-244.5(DUOX2)-251(mutations)]TJ
0 -1.1223 TD
[(are)-468.6(associated)-472.8(with)-464.5(congenital)-469.8(hypothyroidism)-471(with)-464.5(ec-)]TJ
0 -1.1284 TD
[(topic)-375.8(thyroid)-374.2(gland.)-376.5(J)-371.3(Clin)-376.3(Endocrinol)-380.8(Metab)]TJ
/F8 1 Tf
19.1394 0 TD
(102:)Tj
/F3 1 Tf
1.8359 0 TD
(4060)Tj
-20.9753 -1.1223 TD
(4071.)Tj
24.7568 70.8975 TD
[(225.)-500.7(Aycan)-462.1(Z,)-453.4(Cangul)-454.5(H,)-453.1(Muzza)-457.8(M,)-456.9(Bas)-453.8(VN,)-454.9(Fugazzola)-459.6(L,)]TJ
2.2506 -1.1223 TD
[(Chatterjee)-310.3(VK,)-296.3(Persani)-305.9(L,)-301(Schoenmakers)-303(N)-300.6(2017)-299.4(Digenic)]TJ
0 -1.1284 TD
[(DUOX1)-354.7(and)-352.3(DUOX2)-354.7(mutations)-350.1(in)-353.5(cases)-353.1(with)-348.7(congenital)]TJ
0 -1.1223 TD
[(hypothyroidism.)-684.5(J)-682.4(Clin)-687.3(Endocrinol)-685.7(Metab)]TJ
/F8 1 Tf
19.1455 0 TD
(102:)Tj
/F3 1 Tf
9.2951 0 0 9.2951 528.9447 693.8077 Tm
(3085)Tj
-20.9753 -1.1283 TD
(3090.)Tj
-2.2506 -1.1223 TD
[(226.)-500.7(P)-21.3(a)-22.6(r)-20.8(l)-17.9(a)-22.6(t)-17.9(o)-317.3(M)-23.8(,)-317.2(C)-17.1(h)-24.5(a)-16.5(r)-20.8(b)-18.4(i)-24(t)-17.9(-)-20.8(H)-20(e)-22.6(n)-18.4(r)-20.8(i)-17.9(o)-24.5(n)-317.3(F)-15.2(,)-317.2(H)-26.1(a)-16.5(y)-24.5(e)-16.5(s)-316.4(P)-21.3(,)-317.2(T)-20.3(i)-24(b)-18.4(e)-22.6(r)-20.8(t)-17.9(i)-316.7(A)-20(,)-317.2(A)-20(l)-24(o)-18.4(i)]TJ
2.2506 -1.1284 TD
.0212 Tc
[(M,)-277.7(Cucc)4.7(hiara)-275.9(S)-.1(,)-277.7(B)-2(e)4.7(g)-3.3(ue)-282(B)4.1(,)-277.7(Bras)-276.9(M,)-283.8(P)6(o)-3.3(ulie)4.7(t)-283.3(A)1.2(,)-277.7(R)4.1(akotobe)]TJ
0 -1.1223 TD
.0202 Tc
[(S,)-498.3(Ruemmele)-496.5(F,)-492.2(Knaus)-497.5(UG,)-498.3(Cerf-Bensussan)-492.3(N)-493.8(2)-4.3(017)]TJ
0 -1.1284 TD
.0203 Tc
[(Fir)5.6(s)-3.4(t)-546.5(i)-3.7(dentication)-547.1(o)1.9(f)-549.4(b)-4.2(iallelic)-551.3(i)2.4(nherited)-547.1(DUOX2)-553.2(in-)]TJ
0 -1.1223 TD
.0212 Tc
[(activating)-552.3(m)-2.9(utations)-557.5(as)-551.4(a)-562.6(c)4.7(ause)-556.5(of)-554.6(ve)4.7(ry)-558.4(ea)4.7(rly)-552.3(o)2.8(nset)]TJ
0 -1.1284 TD
.021 Tc
[(ina)4.5(mmator)6.3(y)-704.9(b)-3.5(owel)-704.4(dise)]TJ
11.2836 0 TD
.0212 Tc
[(a)4.7(s)-2.4(e.)-704.7(Ga)4.7(stroenter)6.5(o)-3.3(logy)]TJ
/F8 1 Tf
10.3016 0 TD
.0184 Tc
(153:)Tj
/F3 1 Tf
-21.5852 -1.1223 TD
[(6)-6.1(09.e3)-6.1(611.)-6.1(e3)-6.1(.)]TJ
-2.2506 -1.1284 TD
0 Tc
[(227.)-500.7(Muzza)-250.5(M,)-243.4(Rabbiosi)-246(S,)-241(Vigone)-250(MC,)-242.3(Zamproni)-246.5(I,)-246.5(Cirello)-242.4(V,)]TJ
2.2506 -1.1284 TD
[(Mafni)-490.8(MA,)-483(Maruca)-490.8(K,)-483.6(Schoenmakers)-486(N,)-489.7(Beccaria)-486.2(L,)]TJ
0 -1.1223 TD
[(Gallo)-383.5(F,)-381.3(Park)-382(SM,)-380.7(Beck-Peccoz)-384.5(P,)-381.3(Persani)-385.2(L,)-380.3(Weber)-381.8(G,)]TJ
0 -1.1284 TD
[(Fugazzola)-392.5(L)-392.4(2014)-384.8(The)-390.8(clinical)-389.6(and)-388.9(molecular)-392.8(character-)]TJ
0 -1.1223 TD
[(ization)-385.9(of)-386.9(patients)-385.1(with)-385.3(dyshormonogenic)-383.1(congenital)-384.4(hy-)]TJ
0 -1.1284 TD
[(pothyroidism)-251.1(reveals)-252.4(specic)-252.9(diagnostic)-257.3(clues)-251.7(for)-249(DUOX2)]TJ
0 -1.1223 TD
[(defects.)-337.8(J)-334.7(Clin)-333.6(Endocrinol)-338.1(Metab)]TJ
/F8 1 Tf
13.9002 0 TD
(99:)Tj
/F3 1 Tf
1.3296 0 TD
(544553.)Tj
-17.4804 -1.1284 TD
[(228.)-500.7(Lof)-260.8(C,)-255.1(Patyra)-264(K,)-258(Kuulasmaa)-257.6(T,)-258.3(Vangipurapu)-263.4(J,)-255.5(Undeutsch)]TJ
2.2506 -1.1223 TD
[(H,)-282.4(Jaeschke)-290.7(H,)-282.4(Pajunen)-280.1(T,)-282.7(Kero)-283.1(A,)-288.5(Krude)-283.3(H,)-282.4(Biebermann)]TJ
0 -1.1284 TD
[(H,)-349.4(Kleinau)-357.5(G,)-349.4(Kuhnen)-348.2(P,)-350.8(Rantakari)-349.2(K,)-349.5(Miettinen)-354.3(P,)-350.8(Kir-)]TJ
0 -1.1223 TD
[(javainen)-549.4(T,)-544.9(Pursiheimo)-551.2(JP,)-545.2(Mustila)-550.8(T,)-544.9(Jaaskelainen)-550.5(J,)]TJ
0 -1.1284 TD
[(Ojaniemi)-259.1(M,)-249.5(Toppari)-252.8(J,)-249.4(Ignatius)-255.7(J,)-249.4(Laakso)-254.3(M,)-249.5(Kero)-252.7(J)-249.3(2016)]TJ
0 -1.1223 TD
[(Detection)-544.4(of)-533.2(novel)-535(gene)-539.6(variants)-534.4(associated)-539.9(with)-537.7(con-)]TJ
0 -1.1284 TD
[(genital)-239.5(hypothyroidism)-239.2(in)-237.6(a)-242.2(nnish)-234.1(patient)-245.6(cohort.)-238.7(Thyroid)]TJ
/F8 1 Tf
0 -1.1223 TD
(26:)Tj
/F3 1 Tf
1.3357 0 TD
(12151224.)Tj
-3.5863 -1.1284 TD
[(229.)-500.7(Nicholas)-344.6(AK,)-339(Serra)-339.9(EG,)-339.3(Cangul)-338.6(H,)-337.3(Alyaarubi)-341.8(S,)-338.6(Ullah)-334.7(I,)]TJ
2.2506 -1.1223 TD
[(Schoenmakers)-431.1(E,)-423(Deeb)-419.2(A,)-422.6(Habeb)-425.5(AM,)-422(Almaghamsi)-429.4(M,)]TJ
0 -1.1284 TD
[(Peters)-501(C,)-499(Nathwani)-499.5(N,)-501.9(Aycan)-498.6(Z,)-496.1(Saglam)-499.1(H,)-495.8(Bober)-500(E,)]TJ
0 -1.1223 TD
[(Dattani)-326.4(M,)-316.6(Shenoy)-325.1(S,)-320.3(Murray)-320(PG,)-322(Babiker)-320.9(A,)-319(Willemsen)]TJ
0 -1.1284 TD
[(R,)-255.1(Thankamony)-249.2(A,)-251.9(Lyons)-251.8(G,)-245.8(Irwin)-250.3(R,)-255.1(Padidela)-247.3(R,)-255.1(Tharian)]TJ
0 -1.1223 TD
[(K,)-367.7(Davies)-375.4(JH,)-367(Puthi)-368.4(V,)-367.8(Park)-369.8(SM,)-368.5(Massoud)-368.7(AF,)-364.7(Gregory)]TJ
0 -1.1284 TD
[(JW,)-369.8(Albanese)-373.8(A,)-361.6(Pease-Gevers)-377.8(E,)-368.1(Martin)-365.4(H,)-367.7(Brugger)-368.4(K,)]TJ
0 -1.1223 TD
[(Maher)-364.5(ER,)-354.7(Chatterjee)-365.2(VK,)-357.3(Anderson)-356(CA,)-360.5(Schoenmakers)]TJ
0 -1.1284 TD
[(N)-361.6(2016)-354.3(Comprehensive)-361.3(screening)-362.4(of)-356.4(eight)-357.5(known)-356.1(causa-)]TJ
0 -1.1223 TD
[(tive)-491.6(genes)-484(in)-487.6(congenital)-488.1(hypothyroidism)-489.3(with)-482.9(gland-in-)]TJ
0 -1.1284 TD
[(situ.)-334.1(J)-334.7(Clin)-333.6(Endocrinol)-338.1(Metab)]TJ
/F8 1 Tf
12.5034 0 TD
(101:)Tj
/F3 1 Tf
1.8298 0 TD
(45214531.)Tj
-16.5838 -1.1223 TD
[(230.)-500.7(Miyai)-344.6(K,)-337.2(Azukizawa)-344(M,)-341(Kumahara)-346.6(Y)-337.2(1971)-342.1(Familial)-339.1(iso-)]TJ
2.2506 -1.1284 TD
[(lated)-288.6(thyrotropin)-285.1(deciency)-288.8(with)-287.7(cretinism.)-289.6(N)-282.3(Engl)-288.6(J)-279.8(Med)]TJ
/F8 1 Tf
0 -1.1223 TD
(285:)Tj
/F3 1 Tf
1.8359 0 TD
(10431048.)Tj
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