Defnisi

Hypothyroidisme suatu keadaan dimana kelanjar thyroid tidak memproduksi

hormone thyroxin triiodotyronin(T3) dan tetraiodotyronin (T4) dalam jumlah yang
cukup.
Hypothyroidisme terutama disebabkan oleh defsiemsi yodium,namun dapat juga
disebabkan oleh actor lainnya. !ni juga dapat disebabkan oleh berkurangnya
jumlah kelenjar thyroid setelah pembedahan dan juga oleh pengobatan radiasi
!odin "3" pada penderita hyperthyroid. Hypothyroidisme berat pada bayi dapat
menyebabkan kretinisme.
Tanda dan gejala
#eja la hypothyroid dini biasanya asymptomatic atau ringan saja . gejala
hypothyroidTerdiri dari gejala$gejala hyphothyroid dini,gejala hypothyroid
lanjut,gejala hypothyroid yang tidak biasa.
Gejala hypothyroid dini
%enampilan$ kurus, kuku rapuh dan mudah patah& kulit kering dan gatal& berat
badan meningkat, retensi air pada anak,myxedema, kebotakan pada rambut
dikulit kepala dan kulit daerah lain.
#ejala neurologi$ depresi
#ejala neuromuscular$ re'ex menurun, hypotonia, kramp otot, nyeri sendi,
mood tidak stabil, irritability, konstipasi.
#ejala (onstitutional$ lemah,mengantuk,tidak toleransi terhadap
dingin,penurunan jumlah keringat(anhidrosis)
(ardio)ascular$ bradycardia, peningkatan kadar kolesterol darah.
*ndocrine$inertilitas pada +anita, menstruasi tidak teratur,
hyperprolactinemia, and galactorrhea.
Gejala hypothyroid lanjut
Appearance:alis mata 1/3 lateral menipis,wajah bengkak
Neurological: bicara pelan dan suara parau.
Neuromuscular: carpal tunnel syndrome dan paresthesia
Constitutional:temperatur basal rendah
Cardiovascular: hypotension
Endocrine: goiter(gondok),atau gangguan libido pada laki-laki karena gangguan
synthesis testoteron.
Gejal hypothyroid yang tidak biasa
Appearance: kulit kuning,karena gannguan synthesis it ! sehingga terjadi
penumpukan beta carotene,lidah besar
Neurological: gangguan memori,penurunan indera pengecap dan penciuman,tuli.
Neuromuscular: susah menelan,na"as pendek dan dangkal
Cardiovascular:anemia karena terjadi gangguan synthesis hormone erythropoietin,dan
gangguan absorpsi besi,asam "olat,dan itamin #1$
Endocrine:hypoglikemia,gangguan "ungsi ginjal terutama terjadi penurunan
%&'(glomerular "iltration rate)
Penyebab
,ekurangan yodium adalah penyebab hypothyroid yang paling utama.pada area
yang tidak kekurangan yodium penyakit hashimoto merupakan penyebab
utamam,penurunan sekresi T-H oleh hipofsis juga bias menyebabkan
hypothyroid.hypothyroid congenital sangat jarang terutama disebabkan oleh
agenesis kelenjar thyroid
Hypothyroid juga bias disebabkan oleh pengobatan misalnya lithium.obat lainnya
misalnya amiodarone, intereron alpha, interleukin./, riampicin, sunitinib, and
thalidomide.
%aparan terhadap 0at radioakti seperti radioacti)e iodine."3" juga bias
menyebabkan hypothyroid
%ostpartum thyroiditis juga bias menyebabkan hypothyroid
-tress juga bias menyebabkan hypothyroid misaknya karena kadar glukosa yang
tidak stabil atau penurunan ungsi system imun.1. -tress mengganggu H%2 3
thyroid axis,menurunkan perubahan T3 menjadi T4 ,penurunan unsi imun
merangsang terjadinya proses autoimun. %eningkatan kadar kortisol menurunkan
sekresi (T3) .stress juga menurunkan kadar hormone thyroid melalui system
syara symphatis
2drenal insu4ciency juga menyebabkan hypothyroid
Patofsiologi
-ynthesis hormone thyroid memerlukan kadar iodine dan T-H dalam sirkulasi
dalam jumlah yang cukup. !odine kemudian masuk kedalam kelenjar thyroid dan
ikatannya dengan thyroglobulin dilepas.
2xis hypothalamus.hypofsis.thyroid memainkan peran yang penting. T-H
dilepaskan dari hypothalamus, yang kemudian merangsang produksi T-H oleh
kelenjar hypofsis. T-H kemudian merangsang akti)itas kelenjar thyroid. 5ika
hypothalamus atau hypofsis rusak, akan mengganggu akti)itas kelenjar thyroid.
%ada penyakit hashimoto terjadi proses autoimmune terhadap kelenjar thyroid.
Hypothyroid dan kehamilan
Selama kehamulan kebutuhan akan hormone thyroid meningkat,hal ini
menyebabkan terjadinya hypothyroid subklinik pada +anita hamil,dan dapat
berkembang menjadi hypothyroid.
Hypothyroid pada a+al kehamilan meningkatkan terjadinya resiko
preeklampsia,sehingga perlu diberikan suplemen le)othyroxin pada +anita hamil
+alaupun hubungannya lemah namun hypothyroid sangat berhubungan dengan
ertilitas
DIAGNOSIS
6engan cara mengukut kadar T-H,(T3),dan (T4) dalam darah.
%eninggian kadar T-H menandakan kelenjar thyroid tidak memproduksi hormone
thyroxin dalam jumlah yang cukup.. namun pengukuran kadar T-H saja tidak
cukup harus diikuti dengan pengukuran kadar T3 dan T4 darah.tdd$
7ree triiodothyronine (T3)
7ree thyroxine (T4)
Total T3
Total T4
-ebagai tambahan pemeriksaan diba+ah ini juga penting dilakukan$
,adar T3 bebas dalam urin /4 jam.
2ntithyroid antibodies 3 untuk membuktikan apakah ada proses autoimmun
-erum cholesterol 3 meningkat pada kasus hypothyroid
%rolactin .
Test untuk anemia,termasuk pemeriksaan kadar erritin
Temperature basal
,lasifkasi
Type asal
primer #ld.thyroid 8ang paling sering adalah
penyakit hashimoto (penyakit
autoimun)dan pengobatan radiasi
!odin pada kasus hyperthiroid
-ekunder #ld.hypofsis ,arena kelenjar hypofsis tidak
memproduksi cukup T-H untuk
merangsang kelanjar thyroid
dalam memproduksi hormom
thyroxin biasanya disebabkan
oleh kerusakan kelenjar hypofsis
karena tumor,radiasi,atau
pembedahan.
tersier #ld.hypothalamus ,arena hypothalamus tidak
memproduksi T-H dalam jumlah
yang cukup
Penatalaksanaan
Hypothyroidisme diobati dengan preparat le)othorary tdd$thyroxine
(le)othyroxine) (9.T4) and triiodothyronine (liothyronine) (9.T3),T4 saja.

H8%:TH8;:!6!-< != %262 2=2,
,*9*=52; TH8;:!6 terletak dileher setinggi tulang cricoid. Thyroxiine$adalah
hormone yang disekresikan oleh kelenjar thyroid yang berungsi sebagai
pengatur ungsi berbagai organ tubuh.
%ada anak.anak hypothyroid dapat bersiat congenital(telah ada sejak lahir) atau
didapat (terjadi nanti). :leh karena gejalanya tidak langsung tampak dan
onsetnya berlangsung gradual maka hypothyroid sering sekali tidak terdeteksi
2nka kejadian congenital hypothyroidisme adalah sekitar "$3>??.
*tiologi
%ada anak didunia penyebab hypothyroid terutama disebabkan oleh penyakit
autoimmune.sedangkan diindonesia penyebab utamanya adalah defsiensi
yodium
-ymptoms
%ada anak.anak hormone thyroxin sangat berperan dalam mengatur
pertumbuhan sehingga tanda yang paling tampak pada anak.anak yang
kekurangan hormone thyroid berat adalah$menurunnya kecepatan
pertumbuhan.pertumbuhan yang abnormal cenderung menjadi masalah ketika
kelenjar menjadi rusak.
penatalaksanaan
@ /?"" Aritish -ociety or %aediatric *ndocrinology and 6iabetes
Thyroxine tersedia dalam bentuk pil dengan kandungan 0at akti masing.masing
/>, >? or "?? microgrammes .
Thyroxine dalam sediaan ampul juga tersedia dengan dosis />./??ug perhari.
H8%:TH8;:!6!-<* ,:=#*=!T29
%*=62HB9B2=
H8%:TH8;:!6 %262 =*:=2TB-
6efnisi
*pidemiologi
%atogenesis dan patofsiologi
Tanda dan gejala
Test laboratorium
%enatalaksanaan
%rognosis
6*7!-!*=-! T#A
H8%:TH8;:!6!-<* 6!62%2T %262 2=2,
6:!$ "?.">4/Cpir.3?.D./>"
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%ediatrics in ;e)ie+
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Hypothyroidism in (hildren
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Hypothyroidism
in (hildren
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J
2uthor 6isclosure
6rs (ounts and
Farma ha)e disclosed
no fnancial
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o an unappro)edC
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:bjecti)es
2ter completing this article, readers should be able to$
". 6escribe the causes o hypothyroidism in inants and children.
/. 6iscuss the clinical presentation o and diagnostic approach to
hypothyroidism.
3. 6iKerentiate nonthyroidal illness lo+ triiodothyronine (T3) syndrome rom
hypothyroidism.
4. !dentiy thyroid.binding globulin defciency as a euthyroid state.
>. ;ecogni0e the importance o treatment and implications o inadeLuate
treatment o
hypothyroidism in the neonate and young child.
!ntroduction
Thyroid hormone is essential to gro+th and neurologic de)elopment in childhood.
The
thyroid begins to take shape at D +eeksM gestation, and thyroid hormone (T4,
thyroxine)
is produced starting at "/ +eeksM gestation. Thyroid dysunction in the neonate,
inant, or
child has a signifcant impact on de)elopment. The goal o treatment is to assure
normal
gro+th and a)oid de)elopmental delay.
Hypothyroidism in the =eonate
6efnition
=eonatal hypothyroidism results rom decreased T4 production in a ne+born. !t is
the
most pre)entable cause o potential intellectual disability. T4 is critical to the
myelini0ation
o the central ner)ous system ((=-) during the frst 3 years ater birth. !n the
healthy term
baby, serum thyroid.stimulating hormone (T-H) concentrations normally rise
abruptly to
H? to N? mBC9 +ithin 3? to H? minutes ater deli)ery. The serum T-H
concentration
then decreases rapidly to about /? mBC9 by " day o age and subseLuently more
slo+ly to
H to "? mBC9 by " +eek o age. This surge in T-H stimulates T4 secretion, +ith
serum
T4 concentrations peaking at /4 to 3H hours o age at "? to // mcgCd9 ("/N.D to
/N3./ nmolC9). -erum T3 concentrations also rise simultaneously to about />?
ngCd9
(3.E nmolC9), due to increased con)ersion o T4 to T3 in peripheral tissues and
thyroidal
secretion. T4, ree T4, and T3 concentrations gradually all in the frst 4 +eeks
ater birth
to total T4 concentrations o D to "H mcgCd9 (E?." to /?>.E nmolC9), ree T4
concentrations o ?.N to /.? ngCd9 ("?.3 to />.D pmolC9),
and T-H concentrations o ?.E to D.D mBC9, +hich are
higher than adult )alues.
%reterm inants (especially those born at /4 to /D +eeksM
gestation) ha)e smaller increases in serum T-H and ree T4
than do term inants, due to immaturity o the hypothalamic.
pituitary.thyroid axis. %reterm inants ha)e lo+er cord T4
concentrations at birth, and due to their immaturity and
concurrent nonthyroidal illness, the normal postnatal rise o
T4 is delayed. Thereore, the number o abnormal ne+born
thyroid screening test results is disproportionately high in
preterm inants, especially +hen measuring T4 in heel stick
blood specimens.
I
2ssociate %roessor o %ediatrics& (hie, 6i)ision o %ediatric *ndocrinology,
6epartment o %ediatrics, Bni)ersity o <aryland
-chool o <edicine, Aaltimore, <d.
J
*ditorial Aoard.
2bbre)iations
22%$
2merican 2cademy o %ediatrics
(=-$
central ner)ous system
!O$
intellectual Luotient
T3$
triiodothyronine
T4$
thyroxine
TA#$
thyroid.binding globulin
T;H$
thyrotropin.releasing hormone
T-H$
thyroid.stimulating hormone
2rticle
endocrinology
%ediatrics in ;e)ie+
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*pidemiology
-poradic cases o congenital hypothyroidism account or
approximately N>P o cases& ">P are hereditary (autoso.
mal recessi)e). <ore than 4 million inants are screened
yearly in the Bnited -tates, and ",??? inants recei)e the
diagnosis o congenital hypothyroidism each year, an
incidence o approximately " in 4,??? ne+borns. !n one
study, the incidence +as " in 4,??? in +hite inants, " in
/,??? in Hispanic inants, and " in 3/,??? in 2rican
2merican inants. The incidence is t+ice as high in e.
males, and congenital hypothyroidism is more common
in t+ins. The longer the diagnosis and treatment o
congenital hypothyroidism are delayed, the lo+er the
intelligence Luotient (!O) )ersus the expected !O.
%athogenesis and %athophysiology
Thyroid dysgenesis, a group o disorders occurring dur.
ing thyroid de)elopment that includes ectopic thyroid,
thyroid aplasia, and thyroid hypoplasia, occurs in " in
4,>?? babies. Thyroid dysgenesis occasionally is associ.
ated (
>P o cases) +ith other congenital anomalies.
!nborn errors o thyroxine synthesis (dyshormonogen.
esis) are the most common genetic causes o congenital
hypothyroidism, seen in " in 3?,??? babies or "?P o
diagnosed cases. These deects include a deect in thyroid
peroxidase acti)ity (impaired iodide oxidation and or.
ganifcation), abnormalities in iodide transport, produc.
tion o abnormal thyroglobulin molecules, and iodo.
tyrosine deiodinase defciency.
9ess reLuent causes o congenital hypothyroidism
include maternal antibody.mediated hypothyroidism
(" in />,??? to " in "??,???), central hypothyroidism
("in />,??? to " in "??,???), transient hypothyroidism,
iodine defciency (seen in parts o *urope, " in "??),
autoimmune thyroiditis (" in >?,???), and iodide excess
(" in >?,???). !n all these orms o congenital hypothy.
roidism except central hypothyroidism, serum T4 is lo+
and serum T-H is ele)ated. !n central hypothyroidism,
both T4 and T-H are lo+.
(entral hypothyroidism may be associated +ith other
pituitary defciencies, other congenital syndromes (espe.
cially midline deects such as septo.optic dysplasia or
midline clet lip and palate), birth trauma or asphyxia,
and undertreatment o maternal hyperthyroidism (Qges.
tational hyperthyroidismR). =eonatal screening programs
that are based on T-H screening only do not identiy
babies +ho ha)e these orms o congenital hypothyroidism.
(entral hypothyroidism should not be conused +ith
thyroxine.binding globulin (TA#) defciency (" in 4,3??),
+hich causes lo+ serum T4 concentrations +ithout T-H
ele)ation but does not cause hypothyroidism.
!nants +ho are critically ill may ha)e abnormal results
on thyroid unction studies due to nonthyroidal illness
(pre)iously called euthyroid.sick syndrome). !n these
babies, serum T3 is lo+ due to poor peripheral con)er.
sion o T4 to T3, +hich is due to inhibition o >
.
monodeiodination by medications (glucocorticoids, amio.
darone, propranolol, dopamine, dobutamine, urosemide),
cytokines, and other circulating actors induced by the
illness. -erum total T4 is lo+ due to decreased binding to
thyroid.binding proteins, but ree T4 is normal (or e)en
slightly ele)ated) and is measured best by assaying ree T4
by eLuilibrium dialysis. T-H is lo+ during the illness and
typically rises during reco)ery. To distinguish bet+een non.
thyroidal illness and other causes o hypothyroidism, partic.
ularly central hypothyroidism, measurement o T3, ree T4
by eLuilibrium dialysis, and T-H is needed. !n nonthyroidal
illness, the normal ree T4 concentration, as measured by
eLuilibrium dialysis, helps clariy the diagnosis. Thyroid
replacement therapy is not indicated or treatment o non.
thyroidal illness.
%reterm inants +ho ha)e respiratory distress syn.
drome, intrauterine gro+th restriction, and other medi.
cal problems tend not to ha)e the expected postnatal rise
in serum T4, T3, and T-H. T4 and T3 concentrations in
these babies may all ater birth and remain lo+ until they
rise slo+ly as the inant impro)es and gains +eight. -ome
o the all in serum total T4 is due to decreased serum
protein binding (Qhormonal reser)oirR), but serum ree
T4 concentrations are more normal in preterm inants.
-erum T3 concentrations are lo+ because peripheral
con)ersion o T4 to T3 is decreased. T-H concentrations
also are suppressed in sick inants and inants treated +ith
glucocorticoids or dopamine, +hich adds to the decline
in serum T4 and T3 concentrations.
-ymptoms and -igns
<ore than E>P o ne+borns +ho ha)e congenital hypo.
thyroidism ha)e little in the +ay o clinical maniestations
at birth. -ome maternal T4 crosses the placenta, so
inants +ho cannot make any thyroid hormone still ha)e
serum T4 concentrations that are />P to >?P o normal.
Airth length and +eight are +ithin the normal range, but
head circumerence may be increased. 2n open posterior
ontanelle in a term baby may signal congenital hypothy.
roidism. -ymptoms and signs that may be present include
lethargy, hypotonia, hoarse cry, eeding problems, con.
stipation, macroglossia, umbilical hernia, dry skin, hypo.
thermia, and prolonged jaundice. #oiter is uncommon.
=e+borns +ho ha)e congenital thyroid dyshormono.
genesis may ha)e a palpable goiter, but the goiter typi.
cally de)elops later in untreated patients.
endocrinology
hypothyroidism
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9aboratory Tests
7or ne+born screening, most states in the Bnited -tates
use initial T4 testing +ith ollo+.up T-H testing, al.
though some are s+itching to T-H testing. Aet+een
" and 4 days o age, the normal range or serum total
T4 concentrations is "? to // mcgCd9 ("/N.D to
/N3./ nmolC9). Aet+een " and 4 +eeks o age, the
normal range or serum total T4 concentrations is D to
"H mcgCd9 (E?." to /?>.E nmolC9).
-ubclinical hypothyroidism is defned as a normal
serum total or ree T4 concentration and a high serum
T-H concentration. 2lthough agreement is not clear
about +hether to treat subclinical hypothyroidism, +e
recommend that inants +ho ha)e subclinical hypothy.
roidism be treated during the frst 3 years ater birth due
to the critical dependence o the myelini0ing (=- on
thyroid hormone.
;adioiodine scans o the thyroid are recommended by
some experts as part o the initial e)aluation, but these
studies are considered optional in 2merican 2cademy o
%ediatrics (22%) guidelines.
<anagement
The o)erall goals o treatment are normal gro+th and
good cogniti)e outcome. -erum T4 concentrations
should be restored rapidly to the
normal range, ollo+ed by contin.
ued maintenance o euthyroidism.
The aim o treatment is to keep the
serum T4 or ree T4 concentration
in the upper hal o the normal
range adjusted or age. : note,
many commercial laboratories do
not pro)ide age.adjusted normal
ranges in their reports. !n the frst
postnatal year, serum T4 should be
"? to "H mcgCd9 ("/N.D to /?>.E nmolC9) and serum
ree T4 should be ".4 to /.3 ngCd9 ("N.? to /E.H pmolC
9). The serum T-H concentration should be less than
> mBC9.
:ral T4 (le)othyroxine) is the treatment o choice.
The 22% recommends an initial dose o "? to
"> mcgCkg per day, usually 3D.> or >? mcgCday. Ae.
cause term babies +ho +ere started on >? mcgCday
)ersus 3D.> mcgCday had !O scores that +ere "" points
higher, >? mcgCday is recommended or all term and
ull.si0e inants. !n preterm and other lo+.birth+eight
inants, the thyroid replacement dose should be calcu.
lated by using "? to "> mcgCkg per day, +ith the higher
end administered to babies +ho ha)e lo+ T4 concentra.
tions. :nly T4 tablets should be used because thyroid
suspensions prepared by indi)idual pharmacists may re.
sult in unreliable dosing. %arents should be instructed to
crush the T4 tablet and mix it +ith a small )olume o human
milk, ormula, or +ater. -oy ormulas or any preparation
containing concentrated iron or calcium should not be used
because they reduce the absorption o T4.
The more rapidly T4 concentrations are corrected,
the better the neurologic outcome. !n one study, pa.
tients +ho normali0ed their T4 concentrations in e+er
than / +eeks had better cogniti)e, attention, and
achie)ement scores than those +ho took longer to nor.
mali0e thyroid unction. !t also is clear that or more
se)erely aKected babies, a higher initial dose o thyroid
replacement and normali0ation o thyroid unction are
associated +ith better neurologic outcomes. (")
The 22% recommends measurement o serum T4 or
ree T4 and T-H concentrations as ollo+s$

2t / and 4 +eeks ater the initiation o T4 treatment

*)ery " to / months during the frst H postnatal months

*)ery 3 to 4 months bet+een H months and 3 years o age

*)ery H to "/ months thereater until gro+th is complete

/ +eeks ater any change in dose

2t more reLuent inter)als +hen compliance is Lues.

tioned or abnormal results are obtained
2bout "?P to /?P o babies diagnosed as ha)ing
congenital hypothyroidism ha)e transient hypothyroid.
ism. ! the diagnosis o permanent hypothyroidism is not
clear, T4 therapy can be stopped or " month +hen the
child reaches 3 years o age and thyroid unction retested
oK therapy. %ermanent hypothyroidism is confrmed i
the serum T4 )alue is lo+ and the T-H )alue is ele)ated,
and thyroid replacement should be restarted. ! the
T4 and T-H )alues remain normal, hypothyroidism has
been present and no+ is resol)ed.
%rognosis
Aabies born +ith congenital hypothyroidism +ho are
treated adeLuately and promptly (in the frst / to H postna.
tal +eeks) gro+ and de)elop normally. Ghen these children
Aabies
born +ith congenital
hypothyroidism +ho are treated adeLuately
and promptly (in the frst / to H postnatal
+eeks) gro+ and de)elop normally.
endocrinology
hypothyroidism
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are compared +ith children born beore ne+born screening
+as instituted, the psychometric outcome is impro)ed sig.
nifcantly. Ho+e)er, children +ho are treated inadeLuately
in the frst / to 3 years ater birth ha)e !Os belo+ those o
unaKected children. 2 literature re)ie+ o "? studies com.
paring children aSicted +ith more se)ere )ersus moderate
or mild congenital hypothyroidism sho+ed six studies that
reported no diKerence in !O and our studies that reported
a H. to ">.point lo+er !O in the more se)erely aKected
children. (/) 2 group o "N inants +ho +ere inadeLuately
treated in the frst 3 years ater birth (T4 dose
> mcgCkg
per day) due to poor compliance had mean serum T4
concentrations o N.H mcgCd9 (""?.D nmolC9) and a
mean !O score o ND compared +ith a +ell.treated group
+ho had mean serum T4 concentrations o ""./ mcgCd9
(""4./ nmolC9) and a mean !O score o "?>. (3)
:ther studies ha)e ound that e)en +hen there are no
diKerences in global !O scores, subtest components re.
lated to hypothyroidism may ha)e some defciencies.
-ome inants +ho ha)e congenital hypothyroidism, in.
cluding those +hose !O scores are normal, can ha)e
other neurologic problems, including di4culties +ith
gross and fne motor coordination, ataxia, altered muscle
tone, strabismus, decreased attention span, and speech.
2 Toronto screening program ound language defcits at
age 3 years, +hich diminished +ith age, and poor )isual.
spatial and )erbal skills at age > years. (4)
Thyroid.binding #lobulin 6efciency
TA# defciency maniests as the combination o a lo+
serum total T4, lo+ or normal serum ree T4, and normal
T-H concentrations. This entity should be distinguished
rom secondary or tertiary hypothyroidism (lo+ T4 and
QnormalR T-H due to pituitary or hypothalamic hypo.
unction) by assessing ree T4 by eLuilibrium dialysis.
This assay corrects or inaccurate measurement o T4 and
ree T4 in a standard radioimmunoassay due to lo+
concentrations o binding protein. 7ree T4 by dialysis is
a)ailable in the Bnited -tates through t+o commercial
laboratories$ *soterix (9abcorpMs reerence laboratory)
or =ichols (OuestMs reerence laboratory). TA# also can
be measured in serum and is lo+ in most cases. TA#
defciency is an T.linked recessi)e disorder that occurs
in approximately " in 4,3?? ne+borns, predominantly
males. !nants born +ith TA# defciency are euthyroid
and do not reLuire treatment.
(hildhood (2cLuired) Hypothyroidism
6efnition
(hildhood hypothyroidism also is kno+n as acLuired
hypothyroidism. The onset usually is ater H months o
age. The hypothyroidism is caused by ailure o the
hypothalamic.pituitary.thyroid axis, +hich results in de.
creased production o thyroid hormones. The hypothy.
roidism may be primary (at the le)el o thyroid gland),
secondary (at the le)el o pituitary gland), or tertiary (at
the le)el o hypothalamus).
*pidemiology
<ost acLuired childhood hypothyroidism is sporadic.
:nly "?P to ">P o cases are caused by inherited deects
in thyroid gland synthesis or inborn errors o thyroid
metabolism. Hashimoto thyroiditis (autoimmune), the
most common cause o acLuired childhood hypothyroid.
ism, is more common in emales and usually occurs in
early to mid.puberty. The emale.to.male ratio is /$".
The incidence o Hashimoto thyroiditis during adoles.
cence is approximately "P to /P. Hashimoto thyroiditis
may occur by itsel or in association +ith other autoim.
mune diseases such as type " diabetes mellitus, 2ddison
disease, ju)enile idiopathic arthritis, and systemic lupus
erythematosus. Hashimoto thyroiditis occurs commonly
in indi)iduals +ho ha)e 6o+n syndrome or Turner
syndrome.
Aoth genetic and en)ironmental actors contribute to
the pathogenesis o Hashimoto thyroiditis. The autoim.
mune process is belie)ed to start +ith acti)ation o (64
(helper) T lymphocytes specifc or thyroid antigens. The
other causes o acLuired childhood hypothyroidism are
listed in Table ".
(linical 2spects
(linical maniestations include a decline in linear gro+th,
atigue, constipation, cold intolerance, poor school per.
ormance, +eight gain, irregular menstrual periods, and
somnolence (Table /). (hildren aSicted +ith Hashi.
moto thyroiditis also may ha)e other autoimmune disor.
ders and a amily history o thyroid and other autoim.
mune disorders to support the diagnosis.
:ther clinical eatures o acLuired hypothyroidism
include bradycardia, short stature, increased +eight or
height, dry skin, increased body hair, pallor, myxedema
o the ace, an enlarged thyroid gland, proximal muscle
+eakness, delayed relaxation phase o the ankle re'ex,
and delayed puberty. :ccasionally, acLuired childhood
hypothyroidism presents +ith precocious puberty. The
enlarged thyroid gland usually is diKuse and nontender&
sometimes the gland may be frm.
The onset o acLuired childhood hypothyroidism o.
ten is )ery subtle& in retrospect, it may be e)ident that
signs and symptoms +ere present or a longer time,
sometimes or / to 3 or more years. ! pre)ious height
endocrinology
hypothyroidism
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measurements are a)ailable, a decline in linear gro+th
rom the onset o hypothyroidism +ill be e)ident.
%ostablati)e Hypothyroidism
%ostablati)e hypothyroidism may result rom surgery,
therapy +ith radioacti)e iodine, or irradiation. 2ter a
subtotal or total thyroidectomy, hypothyroidism e)entu.
ally maniests. -uch surgery may be indicated or remo)al
o a thyroid neoplasm or or the treatment o #ra)es
disease. <ost children +ho ha)e hyperthyroidism and are
treated +ith radioacti)e iodine de)elop hypothyroidism,
including "?P to /?P in the frst year ater treatment.
2ny irradiation to the neck increases the risk o de)elop.
ing hypothyroidism dose.dependently.
Hypothyroidism 6ue to <edications
2ntithyroid medications such as thionamides, +hich in.
clude propylthiouracil, methima0ole, and carbima0ole,
suppress thyroid unction and lead to hypothyroidism i a
high dose is used or the medication is continued +hen the
childMs hyperthyroidism is in remission. 9ithium, used to
treat bipolar disorder, intereres +ith thyroid hormone syn.
thesis and secretion, leading to hypothyroidism. 2bout one
o three patients taking lithium de)elops subclinical hypo.
thyroidism and one o six de)elops o)ert hypothyroidism.
<ost anticon)ulsant drugs enhance hepatic metabolism
and excretion o thyroxine, +hich could result in hypothy.
roidism, although patients recei)ing such drugs should not
be treated unless the T-H concentration increases.
(hromosomal 6isorders
(hildren +ho ha)e 6o+n syndrome or Turner syn.
drome ha)e a higher incidence o hypothyroidism due to
Hashimoto thyroiditis. -uch patients should recei)e on.
going monitoring or e)idence o hypothyroidism.
!odine 6efciency
!odine defciency is uncommon in =orth 2merica. Ho+.
e)er, iodine defciency associated +ith goiter is the most
common cause o hypothyroidism globally.
9ate :nset o (ongenital Hypothyroidism
9ate onset o mild orms o congenital hypothyroidism
appear ater H months o age. The most common causes
are ectopic gland or one o the inborn errors o thyroid
hormone syntheses.
-econdaryCTertiary Hypothyroidism
(entral hypothyroidism due to hypopituitarism or hy.
pothalamic lesion leads to hypothyroidism that has
subtle clinical eatures. Hypothyroidism can result rom
craniopharyngioma or other tumors pressing on the
hypothalamic.pituitary axis. Hypothyroidism also can
result rom the surgery needed to remo)e the tumor or it
can be caused by cranial irradiation.
Table /.
-ymptoms and -igns o
2cLuired Hypothyroidism

7atigue

(old intolerance

-omnolence

%roximal muscle +eakness

6elayed relaxation phase o ankle re'ex

(onstipation

6elayed gro+th

:)er+eight or height

%allor

(oarse and thick skin

!ncreased body hair

*nlargement o thyroid gland

Aradycardia

!rregular menstrual cycles

6elayed puberty (occasionally precocious puberty)

Table ".
2cLuired Hypothyroidism
%rimary (Thyroid #land)

Hashimoto (autoimmune) thyroiditis

3 !ncreased in some chromosome disorders
3 6o+n syndrome
3 Turner syndrome

%ostablation
3 -urgical
3 ;adioiodine therapy

!rradiation to neck

<edication eKects
3 Thionamides (propylthiouracil, methima0ole,
carbima0ole)
3 9ithium
3 2nticon)ulsants
3 2miodarone

!odine defciency

9ate.onset congenital hypothyroidism

3 Thyroid dysgenesis
3 !nborn errors o thyroid metabolism
-econdary (%ituitary) and Tertiary (Hypothalamus)

(entral hypothyroidism caused by$

3 (raniopharyngioma and other tumors pressing
on hypothalamusCpituitary
3 =eurosurgery
3 (ranial irradiation
3 Head trauma
<iscellaneous

Thyroid hormone resistance

endocrinology
hypothyroidism
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Thyroid Hormone ;esistance
Thyroid hormone resistance is an autosomal dominant
deect due to a mutation in the thyroid hormone recep.
tor beta gene. (linical eatures o hypothyroidism are
present but are due to the ailure o thyroid hormone
concentrations to o)ercome the receptor binding deect.
9aboratory Tests
The common thyroid unction test results diagnostic o
primary hypothyroidism are lo+ serum T4 or lo+ serum
ree T4 concentrations and ele)ated serum T-H concentra.
tions. ! the serum T4 or ree T4 )alue is lo+ and the serum
T-H )alue is normal or lo+, secondary or tertiary hypothy.
roidism may be present but must be distinguished rom
TA# defciency. !n these cases, the diKerence bet+een
secondary and tertiary hypothyroidism can be made on the
basis o a thyrotropin.releasing hormone (T;H) stimula.
tion test. !n the case o secondary hypothyroidism, no
signifcant change in T-H )alues occurs ater administra.
tion o T;H& in hypothalamic (tertiary) hypothyroidism,
T-H )alues increase. !t is important to interpret results
based on the normal range or age. !n
cases o Hashimoto thyroiditis, thy.
roid antibody (thyroid peroxidase
antibody, antimicrosomal antibod.
ies, thyroglobulin antibody) titers are
increased and are diagnostic o
Hashimoto thyroiditis. The use o
ultrasonography and thyroid scan in
the diagnosis o hypothyroidism usu.
ally is not +arranted, but i a nodule is
present, ultrasonography and thyroid
scan may be indicated. 6etermina.
tion o bone age to e)aluate or short
stature may add confrmatory inor.
mation. The 7igure presents a diag.
nostic scheme or e)aluating the
child suspected o ha)ing acLuired
hypothyroidism.
<anagement
(hildhood hypothyroidism is treated
+ith le)othyroxine. The doses or
those ages H to "/ months, " to 3
years, 3 to "? years, and "? to "N
years are > to N, 4 to H, 3 to >, and /
to 4 mcgCkg o body +eight, respec.
ti)ely. Treatment should be indi)id.
uali0ed because the absorption o
T4 and metabolism )ary among indi.
)iduals. -erum ree T4 and T-H con.
centrations should be monitored pe.
riodically, preerably at 3. to H.month inter)als. The goal is
to keep the serum ree T4 concentration at the mid.normal
range and the T-H concentration in the normal range.
:nce the patient is euthyroid, many o the symptoms
disappear.
%rognosis
The prognosis or reco)ering lost linear gro+th depends on
the duration o the hypothyroidism as +ell as the age at
+hich treatment is started. ! the diagnosis is made around
puberty, gro+th may not reco)er ully. -imilarly, i hypo.
thyroidism is longstanding, thyroid replacement +ill not
reco)er all lost stature. ! the onset o childhood hypothy.
roidism occurs ater age / to 3 years, no permanent intel.
lectual damage or neurologic defcit is likely. (hildren +ho
ha)e type " diabetes also should undergo annual thyroid
unction tests to ensure that hypothyroidism has not be.
come part o the autoimmune glandular process. :)erall,
the prognosis o acLuired childhood hypothyroidism is
good i diagnosed in time and hypothyroidism is not o
longstanding duration