boala graves si sarcina

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Therapy Insight: management of Graves diseaseduring pregnancyGrace W Chan and Susan J Mandel*

Continuing Medical Education online

Medscape, LLC is pleased to provide online continuing

medical education (CME) for this journal article,

allowing clinicians the opportunity to earn CME credit.

Medscape, LLC is accredited by the Accreditation

Council for Continuing Medical Education (ACCME) to

provide CME for physicians. Medscape, LLC designates

this educational activity for a maximum of 1.0 AMA PRA

Category 1 CreditsTM. Physicians should only claim credit

commensurate with the extent of their participation in the

activity. All other clinicians completing this activity will

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please go to http://www.medscape.com/cme/ncpand complete the post-test.

Learning objectives

Upon completion of this activity, participants should be

able to:

1 Describe thyroid physiology and hormone levels

during pregnancy.

2 Identify clinical features of Graves disease during

pregnancy.

3 List differential diagnoses for Graves disease during

pregnancy.

4 Describe markers of thyroid status that are most

predictive of thyroid function in fetuses of women

with Graves disease during pregnancy.

5 List signs of fetal hyperthyroidism.

INTRODUCTION

Hyperthyroidism complicates approximately0.10.4% of pregnancies, with 85% of cases dueto Graves disease.1,2 Graves disease, which hasa peak incidence in the child-bearing third tofourth decades, is caused by thyroid-stimulatingantibodies and can be accompanied by auto-immune ophthalmopathy or dermopathy.Treating Graves disease during gestation can becomplex because of the impact of pregnancy both

on the autoimmune course of the disease and onnormal thyroid hormone metabolism. Althoughsubclinical hyperthyroidism has not been impli-cated in adverse pregnancy outcomes, overthyperthyroidism during pregnancy has been asso-ciated with stillbirth, prematurity, pre-eclampsia,and maternal congestive heart failure.35 Somedata have linked significantly elevated maternalserum T4 levels with miscarriage as well.

6Uncontrolled hyperthyroidism during gestationhas been associated with low birth weight and

The diagnosis of Graves disease in pregnancy can be complex becauseof normal gravid physiologic changes in thyroid hormone metabolism.Mothers with active Graves disease should be treated with antithyroiddrugs, which impact both maternal and fetal thyroid function. Optimally,the lowest possible dose should be used to maintain maternal freethyroxine levels at or just above the upper limit of the normal nonpregnantreference range. Fetal thyroid function depends on the balance betweenthe transplacental passage of thyroid-stimulating maternal antibodies and

thyroid-inhibiting antithyroid drugs. Elevated levels of serum maternalanti-TSH-receptor antibodies early in the third trimester are a risk factorfor fetal hyperthyroidism and should prompt evaluation of the fetalthyroid by ultrasound, even in women with previously ablated Gravesdisease. Maternal antithyroid medication can be modulated to treat fetalhyperthyroidism. Serum TSH and either total or free thyroxine levelsshould be measured in fetal cord blood at delivery in women with activeGraves disease, and those with a history of131I-mediated thyroid ablationor thyroidectomy who have anti-TSH-receptor antibodies. Neonatalthyrotoxicosis can occur in the first few days of life after clearance ofmaternal antithyroid drug, and can last for several months, until maternalantibodies are also cleared.

KEYWORDS antithyroid drugs, fetal thyroid dysfunction, Graves disease,neonatal thyroid dysfunction, pregnancy

GW Chan is a Fellow, and SJ Mandel is Associate Professor of Medicine andRadiology, in the Division of Endocrinology, Diabetes, and Metabolism,Department of Medicine, University of Pennsylvania School of Medicine,Philadelphia, PA, USA.

Correspondence*611 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA

[email protected]

Received 27 September 2006 Accepted 24 January 2007

www.nature.com/clinicalpractice

doi:10.1038/ncpendmet0508

REVIEW CRITERIAWe searched PubMed for articles and abstracts between 1965 and 2006 aboutGraves disease and pregnancy. The search terms we used were Graves disease,hyperthyroidism, pregnancy, pregnancy complications, antithyroid drug,fetal thyroid dysfunction and neonatal thyroid dysfunction. All paperswere English-language full text papers. We also searched the reference lists ofidentified articles for further papers.

SUMMARY

CME

470 NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM JUNE 2007 VOL 3 NO 6


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congenital malformations unrelated to antithyroiddrug (ATD) ingestion.5,79

Clearly, proper management is essential for thehealth of both the mother and the fetus. First, wewill discuss maternal thyroid physiology duringpregnancy, the diagnosis and consequences

of maternal Graves disease, and therapeuticoptions for Graves disease. Then we will detailthe ontogeny of the fetal thyroid and discussthe impact of maternal Graves disease and itstherapy on fetal and neonatal thyroid function.

THYROID FUNCTION IN THE MOTHER

Maternal thyroid function tests

During pregnancy, estrogen-induced sialylationof T4-binding globulin (TBG) causes an increasein TBG levels, resulting in an increase in serumtotal T4 concentrations and a decrease in T3 resin

uptake, an indirect measure of TBG capacitythat is inversely proportional to available TBGbinding sites. If a woman is not TBG deficient,then a T3 resin uptake during pregnancy in thenormal nonpregnant reference range is suggestiveof hyperthyroidism.10 As a result of these TBGchanges, normal serum total T4 and T3 levelsthroughout pregnancy are predictably about 1.5times the normal nonpregnant reference range(Figure 1).11

No trimester-specific normal ranges for serumfree T4 (FT4) concentrations exist for commonlyavailable commercial assays. This difficulty iscompounded by the fact that estimates of FT4are method-dependent, and that nonpregnantserum FT4 ranges vary widely. All FT4 assays,even equilibrium dialysis, show a decreasein serum FT4 levels as pregnancy progressescompared with their own nonpregnant referencerange. By the third trimester, serum FT4 levelsare often lower than the normal nonpregnantreference range (Figure 1).12,13

Serum TSH levels also fluctuate duringpregnancy. The increase in thyroid hormonesynthesis mediated by human chorionic gonado-

tropin (hCG) and coinciding with the first-trimester peak in hCG is reflected by a reciprocalfall in serum TSH levels. A 2001 study of Chinesewomen without pre-existing thyroid disease orhyperemesis gravidarum showed that in the firsttrimester, the 95% CI for serum TSH levels was0.032.30 mIU/l.14 Subsequent studies have alsoconfirmed the lower limit of the first-trimesterserum TSH 95% CI to be 0.020.03 mIU/l inhealthy pregnant women.15,16 It is critical forclinicians to recognize this appropriate decrease

in the TSH range during normal pregnancy, asup to 18% of women in the first trimester willhave serum TSH levels below the nonpregnantreference range.17 Median serum TSH levelsthen rise during the second and third trimesters(95% CI 0.033.10 mIU/l and 0.133.40 mIU/l,respectively; Figure 2).14

Diagnosis of Graves disease in pregnancy

Maternal hyperthyroidismThe clinical diagnosis of mild to moderate hyper-thyroidism in pregnancy can be difficult becausepregnant women often exhibit hyperdynamicsigns similar to hyperthyroidism, such as tachy-

cardia, warm, moist skin, heat intolerance, andwide pulse pressure.2 Almost all patients withGraves disease will, however, have a goiter,although ophthalmopathy and dermopathy areonly rarely present.10

In symptomatic patients, serum TSH levelsthat are suppressed below the lower limits of thetrimester-specific ranges, with either elevatedserum FT4 levels or total T4 levels higher than thepregnant reference range, confirm the diagnosisof hyperthyroidism. Differentiation of Graves

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)

Figure 1 Serum total T4 and free T4 levels by trimester. The shaded boxes showinterquartile ranges, with the median value also indicated. Serum total T4 levels

rise to approximately 1.5-times the normal NP reference range. Although

serum free T4 ranges were method-dependent, as shown by the differences

in measurement by the Elecsys (Boehringer Mannheim GmbH, Mannheim,

Germany) and Tosoh (Tosoh Corporation, Yamaguchi, Japan) methods, both

methods show a consistent decrease in free T4 levels as pregnancy progresses.

Figure courtesy of Carole Spencer.13 Abbreviations: 1st, first trimester (n= 105);

2nd, second trimester (n= 39); 3rd, third trimester (n= 64); NP, nonpregnant (n= 62).


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disease from gestational thyrotoxicosis maybe the most common challenge confrontingthe clinician. The absence of a goiter and anti-TSH-receptor antibodies (TRAbs) as well as anormal serum T3 level are, however, suggestiveof gestational thyrotoxicosis, whereas the pres-

ence of a goiter, TRAbs, and thyroid hormonelevels higher than the pregnant reference rangeare consistent with Graves disease.18

Differential diagnosisPatients with Graves disease during pregnancycan present de novo, with recurrence after anATD-induced remission, with exacerbationwhile taking an ATD, or with signs of fetal thyroiddysfunction despite maternal euthyroidism orhypothyroidism after 131I-mediated thyroid

ablation or surgery. Relapse of Graves diseaseduring pregnancy has been associated with shortduration of euthyroidism before pregnancy.19 Inaddition, the course of maternal Graves disease isvariable, with remission in up to 30% of womenby the middle of the third trimester.1,19 The

differential diagnosis also includes toxic adenoma,subacute thyroiditis, excessive thyroid hormoneintake (either factitious or therapeutic), gesta-tional thyrotoxicosis, hyperemesis gravidarum,hydatidiform mole, and choriocarcinoma.1,2

Autoimmune thyroiditis, including postpartumthyroiditis (PPT), can start with a hyperthyroidphase. As PPT may occur up to 1 year afterdelivery or miscarriage, if a woman conceivesagain during that time, hyperthyroidism duringthe first trimester might be due to the hyper-thyroid phase of PPT.20 A hypothyroid phase

can then ensue, so women need to be monitoredclosely for hypothyroidism and initiation oflevothyroxine therapy.

Gestational thyrotoxicosis refers to the hCG-mediated increased production of thyroidhormone that occurs in the late first and earlysecond trimesters at the time of peak hCG secre-tion. Through its subunit, which it shares withTSH, hCG has weak thyrotropic activity. In mostcases, gestational thyrotoxicosis manifests as aserum TSH level below the nonpregnant refer-ence range; however, in hyperemesis gravidarum,up to 60% of women can have suppressed serumTSH and elevated serum FT4 levels, but thesenormalize with resolution of the hyperemesis.21For these conditions, ATDs are generally notrequired, as they have not been shown to improveclinical outcome.

Measurement of antibodiesDifferent assays for maternal TRAbs exist. Themost commonly used radioreceptor assay isthe TSH-binding inhibitory immunoglobulin(TBII) assay. This method detects maternal anti-bodies that displace radiolabeled TSH from the

TSH receptor. In patients with Graves disease,the assumption is that these antibodies stimu-late thyroid hormone production. Such detectedantibodies could, however, potentially block endo-genous TSH stimulation; this effect occurs (rarely)in women with Hashimotos hypothyroidism.The currently available bioassay is the thyroid-stimulating immunoglobulin (TSI) assay, whichmeasures the generation of cyclic adenosine mono-phosphate when the patients serum is incubatedwith cells that express the TSH receptor.

TSH

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TSH

Figure 2 Serum TSH concentrations by trimester.

The 95% CIs are shown by the shaded boxes, with

the median value also indicated. Adapted fromPanesar et al.14 Abbreviations: 1st, first trimester

(n= 55); 2nd, second trimester (n= 62); 3rd, third

trimester (n= 25); NP, nonpregnant (n= 63).


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Antibody patterns generally fluctuate withpregnancy, reflecting the clinical course of thedisease, but can remain stable in patients withlow antibody titers.22 TRAbs can be detectedin the first trimester, but values often decreaseover the second and third trimesters and might

become undetectable before increasing againpostpartum.23,24 Clinically, patients can expe-rience relapse or exacerbation of Graves diseaseby 1015 weeks of gestation. Graves disease can,however, remit late in the second and thirdtrimesters.19 This disease pattern is thoughtto be caused by decreases in stimulating TRAblevels, as described above, rather than increasesin inhibitory TRAb levels.23

THERAPEUTIC OPTIONS

In managing hyperthyroidism during preg-

nancy, it should be remembered that twopatients are being treated: the mother and thefetus. A balance must be made in optimizingtreatment for one without impinging onthe other.

Antithyroid drugs

Methimazole versus propylthiouracilThionamide drugs are considered first-linetherapy. Propylthiouracil and methimazoleare equally effective, and the mean time tonormalization of thyroid function is similar(78 weeks).25 Historically, propylthiouracilwas preferred over methimazole, partly becauseof early experimental data suggesting thatpropylthiouracil, which is more highly protein-bound than methimazole, had more limitedtransplacental passage than methimazole.26Since then, however, other studies have foundthat both drugs readily cross the placenta.27,28In the United States, propylthiouracil isprescribed more frequently than methimazolebecause of possible teratogenic effects linkedto methimazole (see below), but methimazoleand its precursor carbimazole are widely used

throughout the world. There have been no long-term, prospective trials addressing the efficacyof combination levothyroxine and ATD therapyduring pregnancy, and it is currently the standardof care to treat with an ATD alone.

Therapeutic goalsSeveral studies have shown no significantcorrelation between daily maternal ATD doseand fetal thyroid status.2831 Elevation inserum TSH concentration can still be found

in newborns of 23% of mothers taking low-dosepropylthiouracil (100 mg daily or less) and 15%of those taking low-dose methimazole (10 mgdaily or less).29 Studies show instead a strongcorrelation between maternal and neonatallevels of FT4, indicating that maternal thyroid

status is the most clinically practical index offetal thyroid status.30,32 Doses of ATD thatmaintain maternal serum FT4 levels in thenormal nonpregnant reference range mightnot preclude fetal hypothyroidism; appropriateATD doses for the mother might be excessive forthe fetus.22,24,32

Until recently, it was recommended that ATDdoses be individualized such that maternalserum FT4 levels were in the upper third ofor just above the normal nonpregnant refer-ence range.30 An abstract published in 2006

analyzed fetal cord FT4 and TSH levels at birthin relation to maternal serum FT4 levels in 249women with Graves disease who continuedATD therapy through delivery. The authorsreported that low fetal cord blood FT4 levelswere avoided only when the maternal serumFT4 concentration was >1.9 ng/dl (24.5 pmol/l),although one infant whose mothers serumFT4 level was 2.1 ng/dl (27.0 pmol/l) devel-oped central congenital hypothyroidism.32 Thenormal nonpregnant reference range for FT4 inthis study was 0.81.9 ng/dl (10.324.5 pmol/l).ATD doses should therefore be adjusted to main-tain maternal FT4 at or slightly higher (


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Despite this lack of definitive evidence,propylthiouracil, if available, should be usedfor initial therapy, given that there are no casereports of aplasia cutis and only rare anec-dotal reports of embryopathies associatedwith propylthiouracil ingestion.31,37 Since

the introduction of propylthiouracil in the1940s, there has only been one case reported ofneonatal hepatitis and lymphocyte sensitizationattributed to transplacental passage of propyl-thiouracil.38 Long-term follow-up of childrenexposed in utero to ATDs has shown no differ-ence in physical or intellectual developmentcompared to controls.39,40

Propranolol

A useful treatment for hyperthyroid symptomsand preparation for thyroidectomy is -adrenergic

blockade, specifically with propranolol; however,continued propranolol use in pregnancy has beenassociated with fetal growth retardation.41

Iodide

Iodide has not been recommended in the treat-ment of hyperthyroidism during pregnancybecause of its association with neonatal goiterand hypothyroidism when given in conjunctionwith thionamides. One study in which gravidaswith mild Graves disease were treated withlow-dose iodine alone (640 mg daily) showedthat 6% of neonates had elevated serum TSHlevels, but none had a goiter.42 With such littleevidence, iodide should not be considered asprimary therapy, but can be used short-term forthe control of thyrotoxicosis before thyroidec-tomy, or in the management of thyroid storm(see below).

Radioactive iodine

Administration of radioactive iodine for diag-nostic or therapeutic purposes is contraindicatedin pregnancy and lactation. After 1012 weeks ofgestation, once the fetal thyroid has the ability to

concentrate iodine, congenital hypothyroidismcan occur. In one study in which 182 fetuseswere exposed inadvertently to 131I therapyduring the first trimester, pregnancy resultedin 2 (1.1%) spontaneous abortions, 2 (1.1%)intrauterine deaths, 6 (3.3%) hypothyroid chil-dren, and 4 (2.2%) mentally retarded children.43Although the study did not include a controlgroup, the number of children found to behypothyroid was substantially higher than theusual incidence of congenital hypothyroidism,

approximately 1 in 3,000 (0.033%).44,45 It hasbeen suggested that propylthiouracil be admin-istered for 710 days after exposure to decreaseiodide recycling.1

Surgery

Owing to obstetric and fetal risks, surgery isnot regarded as first-line therapy, but might beconsidered if necessary for the mothers health.Indications for surgery include the require-ment for continued large doses of ATDs (propyl-thiouracil >450 mg, methimazole >30 mg),goiters causing symptoms of dysphagia or airwayobstruction, and noncompliance with or severereaction to medical therapy. Surgery duringthe first trimester has been associated with anincreased rate of spontaneous abortions.46 Ifpossible, therefore, surgery should be post-

poned until the second trimester. Preoperativepreparation includes ATD therapy (if notcontraindicated), short-term use of iodides, and-adrenergic blockade. Thyrotoxicosis should becontrolled as best as possible to lower the risk ofthyroid storm.

Thyroid storm

With a reported incidence of 12% of all thyro-toxicosis cases, thyroid storm during pregnancycan be triggered by pre-eclampsia, placentaprevia, labor, Cesarean section, or infection.1,10This is a life-threatening condition character-ized by severe symptoms of hyperthyroidism,fever (as high as 41C), and alteration in mentalstatus. Early treatment is essential and includesATDs, iodide, corticosteroids, -adrenergicblockade, cooling measures, and treatment ofthe precipitating cause.1 As propylthiouracilblocks the peripheral conversion of T4 to T3,it is usually preferred over methimazole. Dosesmight need to be given through a nasogastrictube, or by rectal suppository, if the patient isunable to take medications by mouth.1 Iodideshould be given at least 1 h after the ATD so that

it is not used for continued hormone synthesis.Dexamethasone can also be used to block theperipheral conversion of T4 to T3.

1,10 Fetalmonitoring should be performed continuouslyif the fetus is viable.

THYROID FUNCTION IN THE OFFSPRING

Fetal thyroid function

By 1012 weeks gestation, with the increasedexpression of the sodium iodide symporter gene,the fetal thyroid is capable of concentrating


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iodide, accumulating colloid, and producingthyroglobulin.47,48 At around 20 weeks of gesta-tion, the TSH receptor is capable of respondingto TSH (as well as thyroid-stimulating anti-bodies).47,49 The placenta is not permeable toTSH but is so to iodide.47 Active iodide trans-

port across the placenta can occur as well, assuggested by the expression of the sodium iodidesymporter gene in trophoblasts, although themechanism has not been fully elucidated.5052Particularly in the second half of pregnancywhen the fetal thyroid produces T4, adequatematernal intake of iodine is crucial as asubstrate for fetal thyroid hormone synthesis.The placenta also contains the Type 3 deio-dinase, which inactivates much of the T4 andT3 from the maternal circulation and providesa secondary source of iodine for the fetus.47

Maternal T4 crosses the placenta throughoutgestation. This amount is biologically signifi-cant, particularly in the first trimester beforefetal thyroid hormone production.2,53,54

Fetal thyroid dysfunction

Diagnosis of fetal thyroid dysfunction is chal-lenging. Although transplacental passage ofmaternal antibodies (IgG class) to the fetusdoes occur early in gestation, the fetal concen-tration is quite low until the end of the secondtrimester. Placental permeability to theseimmunoglobulins then increases such thatin the last trimester, fetal levels are equivalentto maternal.55 This change in permeability,coupled with the ability of the fetal thyroid torespond to TSH and TRAbs, explains why fetalhyperthyroidism occurs in the second half ofpregnancy. In women with Graves diseasereceiving ATD therapy, fetal thyroid hormonesynthesis therefore represents the balancebetween the transplacental passage of theinhibitory maternal ATD and concentrationsof maternal thyroid-stimulating TRAbs.

Fetal thyroid ultrasound at 32 weeks to screen

for clinically relevant fetal thyroid dysfunc-tion has a reported sensitivity of 92% and aspecificity of 100%;22 however, if a fetal goiteris detected, fetal hyperthyroidism and hypo-thyroidism must be differentiated (Figure 3).Signs suggestive of fetal hyperthyroidism includeintrauterine growth retardation, arrhythmias,congestive heart failure, advanced bone age, cranio-synostosis, and hydrops.49,56 Another suspiciousfeature is a diffuse Doppler ultrasound signalthroughout the thyroid gland.57 Tachycardia

(>160 beats per minute) can indicate, but is notalways present in, fetal thyrotoxicosis.22,58,59Fetal hypothyroidism can be difficult to diag-nose. Studies have suggested criteria includinga Doppler ultrasound signal in the peripheryof the fetal thyroid gland and retarded bonematuration.22,57,59

As the maternal thyroid is influenced by thesame factors (the inhibitory ATD and stimu-lating TRAbs) as the fetal thyroid, maternalthyroid hormone levels might be indicativeof fetal thyroid function.30,32 Extremely highTRAb concentrations associated with poorcontrol of maternal hyperthyroidism usually,therefore, indicate fetal hyperthyroidism, buthigh maternal ATD doses coupled with lowTRAb levels have been associated with fetalhypothyroidism.22 If a fetal goiter indicatinghypothyroidism is caused by maternal ATDingestion, a dosage reduction or discontinua-tion leads to improvement in, and sometimes

resolution of, the goiter that can be documentedby serial ultrasounds.57,6062 There have alsobeen case reports of weekly intra-amnioticlevothyroxine therapy resulting in improvedthyroid function on cordocentesis and preven-tion of goiter at delivery, but this treatment hasbeen accompanied by simultaneous reductionin maternal ATD therapy.61

In addition, fetuses of levothyroxine-replacedwomen with a history of131I-mediated thyroidablation or surgery for Graves disease are also at

Fetal goiter

1 ATD-treated maternalGraves disease with maternalserum free T4 in normal

laboratory reference range

2 Normal or low TRAb

3 Delayed fetal bone age

1 Poorly controlled maternalhyperthyroidism

2 Levothyroxine-replacedmaternal hypothyroidism after131I-mediated ablation orthyroidectomy, with elevatedTRAb

3 Fetal tachycardia

4 Advanced fetal bone age

Fetal hypothyroidism:risk factors

Fetal hyperthyroidism:risk factors

Figure 3 Differentiation between fetal hypothyroidism and hyperthyroidism

in the presence of a fetal goiter. Abbreviations: ATD, antithyroid drug;

TRAb, maternal anti-TSH-receptor antibody.


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risk for hyperthyroidism. Unknown to clinicianand patient, the continued maternal productionof high levels of TRAbs could stimulate the fetalthyroid without the presence of the temperingeffect of ATDs. These women should thereforehave TRAb levels measured at 2628 weeks

gestation and, if levels are elevated, a fetalthyroid ultrasound should be performed.63There have been multiple reports of pregnan-cies in which fetal hyperthyroidism was treatedwith ATDs.6466 Maternal daily ATD doseshave ranged between 50 and 300 mg for propyl-thiouracil, and 15 and 40 mg for methimazole orcarbimazole. For levothyroxine-replaced hypo-thyroid women, the maternal levothyroxine dosemight need to be increased as well. Althoughthe optimal timing for ATD administration isuncertain, the cases reported initiation of ATDs

between 20 and 34 weeks. Doses can be modu-lated clinically and decreased when the fetalheart rate normalizes.65,66

Umbilical cord blood sampling, also calledcordocentesis or funipuncture, can be reservedfor cases in which definitive diagnosis of fetalthyroid dysfunction is still in doubt afterultrasound. The procedure should, however,only be performed in centers with experi-ence. It has been associated with a 0.52.0%risk of fetal bleeding, bradycardia, infection,and death.67,68

Neonatal thyroid dysfunction

Neonatal thyrotoxicosis due to persistenceof maternal TRAbs occurs in about 1% ofbabies born to mothers with either active orpreviously treated Graves disease and lastsfor up to 3 months.69 Multiple studies haveattempted to predict neonatal thyroid statususing maternal antibody levels. Strong corre-lation has been found between maternal andfetal TSI and TBII levels.24,70 Maternal TSIs>350500% (normal 4070% (normal


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KEY POINTS

First-line therapy for Graves disease during

pregnancy includes antithyroid drugs

(preferably propylthiouracil)

Prescribed doses should be as low as possible

to maintain maternal serum free T4 levels at

or just above the upper limit of the normalnonpregnant range, or total T4 levels at 1.5-

times the normal nonpregnant reference range

If continued administration of antithyroid

medication is not possible, second-trimester

thyroidectomy can be considered; patients

should receive -adrenergic blockade and

iodide therapy preoperatively

All women with active Graves disease, and

levothyroxine-replaced patients with a history

of 131I-mediated ablation or thyroidectomy,

should have their anti-TSH-receptor antibody

(TRAb) levels measured at 2628 weeks

gestation to evaluate the risk for fetal

hyperthyroidism

To assess fetal thyroid function, fetal

ultrasound at 2832 weeks should be

performed if there is evidence of active

maternal Graves disease (elevated maternal

TRAb levels, or maternal requirement for

antithyroid medication)

Serum TSH and total T4 or free T4

concentrations should be measured in fetal

cord blood at delivery in women with active

Graves disease or positive TRAb screen after

131I-mediated ablation or thyroidectomy


9/9

REVIEW



Acknowledgments

GW Chan is supported

by NIH grant 2-T32-

DK007314-26. We thank

C Spencer for supplying

the data used for Figure 1.

Dsire Lie, University

of California, CA, is the

author of and is solely

responsible for thecontent of the learning

objectives, questions and

answers of the Medscape-

accredited continuing

medical education activity

associated with this article.

Competing interestsThe authors declared

they have no competing

interests.

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