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Journal of Thyroid ResearchVolume 201! "rticle #$ %&%'(&! ( pages
http)**d+,doi,org*10,11--*201*%&%'(&
Review Article
Management of Hyperthyroidism in Pregnancy:
Comparison of Recommendations of American ThyroidAssociation and Endocrine Society
Shahram Alamdari, Fereidoun Aii, Hossein !elshad, FaranehSar"ghadi, Atieh Amouegar, and #adan Mehran
Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of
Medical Sciences, Tehran 199!"#$%, Iran
Correspondence should be addressed to .hahram "lamdari/ alamdariendocrine,ac,ir
Receied % $ecember 2012/ "ccepted 1 arch 201
"cademic 3ditor) John H, 4a5arus
Copyright 6 201 .hahram "lamdari et al, This is an open access article distributed under the Creatie Commons
"ttribution 4icense! which permits unrestricted use! distribution! and reproduction in any medium! proided the
original wor7 is properly cited,
"ppropriate diagnosis and treatment of hyperthyroidism during pregnancy are of outmost importance! because hyperthyroidism
has ma8or aderse impact on both mother and fetus, .ince data on the management of thyroid dysfunction during pregnancy is
rapidly eoling! two guidelines hae been deeloped by the "merican Thyroid "ssociation and the 3ndocrine society in the last 2
years, 9e compare here the recommendations of these two guidelines regarding management of hyperthyroidism during
pregnancy, The comparison reeals no disagreement or controersy on the arious aspects of diagnosis and treatment of
hyperthyroidism during pregnancy between the two guidelines, Propylthiouracil has been considered as the first:line drug for
treatment of hyperthyroidism in the first trimester of pregnancy, #n the second trimester! consideration should be gien to switching
to methima5ole for the rest of pregnancy, ethima5ole is also the drug of choice in lactating hyperthyroid women,
$% &ntroduction
$iagnosis of hyperthyroidism which occurs in 0,0- to ,0;
of pregnancies may be difficult in these women! as the
symptoms and signs of nerousness! sweating! dys:pnea!
tachycardia! and cardiac systolic murmur are seen in most
normal pregnancies as well raes? hyperthyroidism
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Therefore estimation of DT'inde+ may be employed! but
international reference ranges hae not been aailableuntil recently and only one manuscript is underpublication
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2 Journal of Thyroid Research
Tabel 1) Perbandingan rekomendasi dari Asosiasi Thyroid Amerika dan Perhimpunan Endokrin pada
tatalaksana hipertiroidisme sebelum kehamilan dan pada diagnosis hipertiroidisme dan kehamilan.
Topik
Re7omendasi
"merican Thyroid "ssociation @2011A 3ndocrine .ociety @2012A
Dor oert hyperthyroidism due to >raes?disease
or thyroid nodules! antithyroid drug @"T$A
therapy should be either initiated @beforepregnancy if possible! and for those withnew
Tatala7sanasebelum 7ehamilan
.ama @R and TA
diagnosesA or ad8usted @for those with aprior
historyA to maintain the maternal thyroid
hormone leels for free T' at or 8ust aboethe
upper limit of the nonpregnant reference range!orto maintain total T' at 1,- times the upper limitofthe normal reference range or the free T' inde+in
,
#n the presence of a suppressed serum T.H inthe
Thyroid function
first trimester @T.H G0,1 m#*4A! a historyand
physical e+amination are indicated, DT'
.ame @RA
testsmeasurements should be obtained in allpatients,
easurement of TT and TR"b may be helpfulin
establishing a diagnosis of hyperthyroidism,
There is not enough eidence to recommendfor
ltrasonography
or against the use of thyroid ultrasound in
Ionedifferentiating the cause of hyperthyroidismin
pregnancy,
.canning and
Radioactie iodine @R"#A scanning orradioiodine
upta7e determination should not be performedin Ione
upta7epregnancy,
$ifferentiation of
$ifferentiation of >raes? from gestational
thyroto+icosis is supported by the presenceof
>raes disease
.ame @TAclinical eidence of autoimmunity! typicalgoiter!and gestationaland presence of T.H receptor antibodies @TR"bA,
thyroto+icosis
TPB:"b may be present in either case,
by "merican Thyroid "ssociation and 3ndocrine .ociety!
respectiely, #t is the aim of this paper to compare the
recom:mendations of these two guidelines regarding
management of hyperthyroidism during pregnancy,
'% Methods
The section of thyroto+icosis in pregnancy! pages 10EF10E( of
the >uidelines of the "merican Thyroid "ssociation
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fetus aspects! pages 2--0F2-- of the 3ndocrine .ociety
Clinical Practice guidelines uidelines posed 1' uestions and responses were
gathered to 1' recommendations uidelines! a total of 1 recommen:
dations were gien for the management of hyperthyroidism in
pregnancy! including - recommendations for management of
maternal aspects of hyperthyroidism! - for management of fetal
aspects! and for gestational hyperemesis and hyper:
thyroidism raes? disease
and gestational thyroto+icosis! T.H receptor antibod:ies @TR"bA
determination had been recommended,
Table 2 compares recommendations of "T" and 3ndo:
crine .ociety on the management of hyperthyroidism during
pregnancy, The use of propylthiouracil @PTA has been rec:
ommended by both organi5ations during the first trimester
of pregnancy! followed by methima5ole @#A after the first
trimester, 3ndocrine society guideline states that # may
be prescribed if PT is not aailable or if a patient cannot
tolerate or has an aderse response to PT and it alsorecommends that practitioners should use their clinical
8udgment in switching patients from one drug to another,
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Journal of Thyroid Research
Table 2) Comparison of recommendations of "merican Thyroid "ssociation and 3ndocrine .ociety on the treatment of
hyperthyroidism in pregnancy,
Topic
Recommendations
"merican Thyroid "ssociation @2011A 3ndocrine .ociety @2012A
PT is preferred for the treatment of
"ntithyroid @"T$A
hyperthyroidism in the first trimester! andpatients on # should be switched toPT if
treatmentpregnancy is confirmed in the firsttrimester,Dollowing the first trimester! considerationshould
be gien to switching to #,
Propylthiouracil @PTA! if aailable! is
recommended as the first:line drug for treatment ofhyperthyroidism during the first trimester of
pregnancy because of the possible association of
methima5ole @#A with specific congenital
abnormalities that occur during first trimester
organogenesis! and # may also be prescribed if
PT is not aailable or if a patient cannot tolerate
or has an aderse response to PT, Practitioners
should use their clinical 8udgment in choosing the
"T$ therapy! including the potential difficulties
inoled in switching patients from one drug to
another, #f switching from PT to #! thyroid
function should be assessed after 2 wee7s and
then at 2: to ':wee7 interals,
Combination of 4T'and
" combination regimen of T' and an "T$should
not be used in pregnancy! e+cept in the rare Ione
"T$
situation of fetal hyperthyroidism,
onitoring lierfunction
"lthough lier to+icity may appear abruptly! itis
Ione
reasonable to monitor lier function inpregnant
in women on PTwomen on PT eery :' wee7s and toencouragepatients to promptly report any new
symptoms,#n women being treated with "T$s inpregnancy!
onitoring of thyroid
DT' and T.H should be monitoredappro+imately
eery 2F( wee7s, The primary goal is a serumDT' .ame @TA
function
at or moderately aboe the normal reference
range,
.ubtotal thyroidectomy may be indicatedduringpregnancy as therapy for maternal >raes?disease
if @1A a patient has a seere aderse reactionto
.urgery .ame @R and TA
"T$ therapy @2A persistently high doses of"T$are reuired @oer 0 mg*d of # or '-0 mg*dofPTA or @A a patient is nonadherent to
"T$therapy and has uncontrolledhyperthyroidism,The optimal timing of surgery is in thesecond
trimester,
Combinations of regiment of T' with antithyroid drugs
hae not been recommended and an indication of
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surgery has been described by both guidelines, Bnly
3ndocrine .ociety guide:line recommends lier function
tests in pregnant women on PT eery :' wee7s,
Comparison of two recommendations on fetalaspects of hyperthyroidism in pregnancy is almostsimilar @Table A! stressing the importance ofmeasurement of TR"b at 20F2' wee7s of gestation!consulation with and e+pert obstetrician! and followingup of fetal thyroid dysfunction,
Table ' compares the recommendations of bothorgani:5ations on the management of gestationalhyperthyroidism, They recommend supportie therapyand aoidance of antithyroid therapy, Loth guidelinesstate that subclinical hyperthyroidism duringpregnancy does not reuire any treatment,
)% !iscussion
>raes? disease is the most common cause of autoimmune
hyperthyroidism in pregnancy, #t has been reported in about
0,-; of pregnancies, #t may be the first manifestation of the
disease or may present as a recurrent episode in a woman
with past history of hyperthyroidism! or a pregnancy in a
women on antithyroid drugs ! to+ic adenoma! and facti:
tious hyperthyroidism, ore freuent than >raes? disease
as the cause of hyperthyroidism is the syndrome of
gestational hyperthyroidism or gestational transient
thyroto+icosis! diag:nosed in about F-; of pregnancies
and includes women with hyperemesis graidarum! multiple
pregnancies! and hydatidiform mole raes?
disease is e+acerbated during the f irst trimester of gestation
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' Journal of Thyroid Research
Table ) Comparison of recommendations of "merican Thyroid "ssociation and 3ndocrine .ociety on the fetal aspects of
hyperthyroidism in pregnancy,
Topic
Recommendations
"merican Thyroid "ssociation @2011A 3ndocrine .ociety @2012A
#f the patient has a past or present history of
TR"b should be measured by 22:wee7gestational
Thyroid receptorantibodies
age in mothers with @1A current >raes? disease/or
>raes? disease! a maternal serumdetermination
@2A a history of >raes? disease and treatmentwith
@TR"bAof TR"b should be obtained at 20F2'wee7s
11# or thyroidectomy before pregnancy/@A a
gestation,preious neonate with >raes? disease/ or@'A
preiously eleated TR"b
#n women with TR"b or thyroid:stimulating#geleated at least 2: to :fold the normal leel
and
Detal sureillance with serial ultrasoundsshould
in women treated with "T$! maternal freeT'!
and fetal thyroid dysfunction should bescreenedbe performed in women who hae
uncontrolled for during the fetal anatomy ultrasound doneinhyperthyroidism and*or women with high
TR"b the 1%thF22nd wee7 and repeated eery 'F(wee7sleels @greater than three times the upper limit
of
Detal .ureillance
or as clinically indicated, 3idence of fetalthyroid
normalA, " consultation with an e+perienced dysfunction could include thyroidenlargement!obstetrician or maternal:fetal medicine
specialist growth restriction! hydrops! presence ofgoiter!
is optimal, .uch monitoring may include adanced bone age! tachycardia! or cardiacfailure!ultrasound for heart rate! growth! amniotic
fluid if fetal hyperthyroidism is diagnosed andthought
olume! and fetal goiter, to endanger the pregnancy! treatment using#or PT should be gien with freuentclinical!
laboratory! and ultrasound monitoring,
Cordocentesis should be used in e+tremelyrare
circumstances and performed in anappropriate
mbilical bloodsampling
setting, #t may occasionally be of use whenfetal
.ame @RAgoiter is detected in women ta7ing "T$s tohelpdetermine whether the fetus is hyperthyroidor
hypothyroid,
"ll newborns of mothers wi th >raes?disease
3aluation of newborn .ame @TA @e+cept those with negatie TR"b and notreuiring "T$A should be ealuated by a
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medicalcare proider for thyroid dysfunction andtreated
if necessary,
Table ') Comparison of recommendations of "merican Thyroid "ssociation and 3ndocrine .ociety on other aspects of
hyperthyroidism in pregnancy,
Topic
Recommendations
"merican Thyroid "ssociation @2011A 3ndocrine .ociety @2012A
ost women with hyperemesis graidarum!clinicalhyperthyroidism! suppressed T.H! and eleatedfree
The appropriate management of womenwith
T' do not reuire "T$ treatment, Clinical8udgment
should be followed in women who appeargestational hyperthyroidism andhyperemesis
significantly thyroto+ic or who hae inaddition
anagement of
graidarum includes supportie therapy!serum total T alues aboe the reference rangefor
management of dehydration! andhospitali5ation pregnancy, Leta bloc7ers such as metoprolol maybe
gestational
if needed,helpful and may be used with obstetricalagreement,
hyperthyroidism "T$s are not recommended for themanagement 9omen with hyperemesis graidarum and
of gestational hyperthyroidism,diagnosed to hae >raes? hyperthyroidism @freeT'
.ame @TAaboe the reference range or total T' M1-0; oftopnormal pregnancy alue! T.H G0,01 m#*liter!andpresence of TR"bA will reuire "T$ treatment!as
clinically necessary,There is no eidence that treatment ofsubclinical
.ubclinical hypothyroidism .ame @TA
hyperthyroidism improes pregnancy outcome!and
treatment could potentially adersely affectfetal
outcome,
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Journal of Thyroid Research
and decreased during the latter half of pregnancy! to
be e+ac:erbated again shortly after deliery or late in
the postpartum period concentration! and hC> thyroid stimulation withsuppression of serum T.H! may pause difficulties inthe diagnosis of maternal hyperthy:roidism raes? disease
reen! , "baloich! 3, "le+ander et al,!>uide:lines of the "merican Thyroid "ssociation for the
diagnosis and management of thyroid disease during
pregnancy and postpartum!K Thyroid! ol, 21! no, 10! pp,
10%1F112-! 2011,
[11] 4, $e >root! , "baloich! 3, O, "le+ander et al,!anagement of thyroid dysfunction during pregnancy and
postpartum) an endocrine society clinical practice guideline!K
ournal of ClinicalEndocrinolo(y ' Meta)olis*! ol, E&! no, %! pp,
2-'F2-(-! 2012,
[12] O, Patil:.isodia and J, H, estman! >raeshyperthyroidism and pregnancy) a clinical update!K
Endocrine &ractice! ol, 1(! no, 1! pp, 11%F12E! 2010,
[13] J, N, 4, Tan! O, C, 4oh! >, ., H, Neo! and N, C,Chee! Transient hyperthyroidism of hyperemesis
graidarum!KAn Internationalournal of -)stetrics and
.ynaecolo(y! ol, 10E! no, (! pp, (%F(%%! 2002,
[14] I, "mino! B, Tani5awa! H, ori et al,! "ggraation
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of thy:roto+icosis in early pregnancy and after deliery
in >raes? disease!K ournal of Clinical Endocrinolo(y
' Meta)olis*! ol, --! pp, 10%F112! 1E%2,
[15] J, H, 4a5arus! Thyroid disorders associated withpregnancy) etiology! diagnosis! and management!K
Treat*ents in Endo"crinolo(y! ol, '! no, 1! pp, 1F'1! 200-,
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(
[16] $, >linoer! Thyroid hyperfunction duringpregnancy!K Thyroid! ol, %! no, E! pp, %-EF%('! 1EE%,
[17] 4, O, illar! $, ", 9ing! ", ., 4eung! P, P, Ooonings! , I,ontoro! and J, H, estman! 4ow birth weight and preeclamp:
sia in pregnancies complicated by hyperthyroidism!K -)stetrics
and .ynecolo(y! ol, %'! no, (! pp, E'(FE'E! 1EE',
[18] P, Papendiec7! ", Chiesa! 4, Prieto! and 4, >runeiro:Papendiec7! Thyroid disorders of neonates born to mothers
with >raes? disease!K ournal of &ediatric Endocrinolo(y and
Meta)olis*! ol, 22! no, (! pp, -'&F--! 200E,
[19] , Phoo8aroenchanachai! ., .riussadaporn! T,Peerapatdit et al,! 3ffect of maternal hyperthyroidism
during late pregnancy on the ris7 of neonatal low birth
weight!K Clinical Endocrinolo(y! ol, -'! no, ! pp, (-F&0!
2001,
[20] $, 4uton! #, 4e >ac! 3, Vuillard et al,! anagement of>raes? disease during pregnancy) the 7ey role of fetal
thyroid gland monitoring!K ournal of Clinical Endocrinolo(y
and Meta)olis*! ol, E0! no, 11! pp, (0EF(0E%! 200-,[21] I, omotani! J, Ioh! and H, Byanagi! "ntithyroid
drug therapy for >raes? disease during pregnancy)
optimal regimen for fetal thyroid status!K /ew En(land
ournal of Medicine! ol, 1-! no, 1! pp, 2'F2%! 1E%(,
[22] $, Peleg! ., Cada! ", Peleg! and , Len:"mi! Therelationship between maternal serum thyroid:stimulating
immunoglobulin and fetal and neonatal thyroto+icosis!K -)stetrics
and .ynecol"o(y! ol, EE! no, (! pp, 10'0F10'! 2002,
[23] I, Qwaeling:.oonawala! P, an Trotsenburg! andT, Vulsma! Central hypothyroidism in an infant born to
an adeuately treated mother with >raes? disease) an
effect of maternally deried thyrotrophin receptor
antibodiesK Thyroid! ol, 1E! no, (! pp, ((1F((2! 200E,[24] D, "5i5i! Treatment of post:partum thyroto+icosis!K ournal of
Endocrinolo(ical Investi(ation! ol, 2E! no, ! pp, 2''F2'&! 200(,
[25] D, "5i5i and , Hedayati! T hyroid function in breast:fed infants whose mothers ta7e high doses of
methima5ole!K ournalof Endocrinolo(ical Investi(ation!
ol, 2-! no, (! pp, 'EF'E(!2002,
[26] D, "5i5i! , Lahrainian! , 3, Ohamseh! and , Ohoshniat!#ntellectual deelopment and thyroid function in children who
were breast:fed by thyroto+ic mothers ta7ing methima5ole!K
ournal of &ediatric Endocrinolo(y and Meta)olis*! ol,1(! no,E! pp, 12EF12'! 200,
[27] D, "5i5i! Thyroid function in breast:fed infants is notaffected by methima5ole:induced maternal hypothyroidism)results of a retrospectie study!K ournal of Endocrinolo(ical
Investi(ation! ol, 2(! no, '! pp, 01F0'! 200,
[28] D, "5i5i and , Hedayati! T hyroid function in breast:fed infants whose mothers ta7e high doses of
methima5ole!K ournalof Endocrinolo(ical Investi(ation!
ol, 2-! no, (! pp, 'EF'E(!2002,
Journal of Thyroid Research
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