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Hyperthyroidism and pregnancy

Hyperthyroidism and pregnancy



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Hyperthyroidism and pregnancy
Hyperthyroidism and pregnancy

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Published by: Prof Dr Dr Ernst Hanisch on Mar 30, 2008
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Helen Marx, Pina Amin and John H Lazarus
Hyperthyroidism and pregnancy
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on 30 March 2008bmj.comDownloaded from 
Hyperthyroidism and pregnancy
Helen Marx,
Pina Amin,
 John H Lazarus
Pregnant women with hyperthyroidismneed careful management as some may beatincreasedriskoffetalloss,pre-eclampsia,heartfailure,prematurelabour,andhavingalow birthweight baby
Various problems may arise in the management of a pregnant patient with hyperthyroidism (see scenariobox p 666).
This article will explore the problems inrelation to the prevalence of hyperthyroidism inpregnancy, therapeutic issues, pregnancy planning,and clinical management. No controlled trials of management have been conducted, but consensusguidelines have recently been published.
How common is hyperthyroidism in pregnancy?
Hyperthyroidism occurs in 2/1000 pregnancies in theUnited Kingdom.
hyperthyroidism (definedas hyperthyroidism that is the result of stimulation of the thyroid by thyrotrophin receptor stimulating anti-bodies (TRAb)) is the commonest cause of hyper-thyroidisminyoungwomen(about85%ofcases)intheUnited Kingdom.
The prevalence of undiagnosedhyperthyroidism in women is about 4.7/1000,
and0.2% of UK women have been previously diagnosedand treated. In areas of mild iodine deficiency theprevalence is higher.
Box 1 outlines the causes of hyperthyroidism in pregnancy.In addition to true hyperthyroidism, the morecommon clinical entity of transient gestationalhyperthyroidism may be seen particularly in the first trimester,withaprevalenceinEuropeansof2-3%buta much higher prevalence in South Asian populations.Hyperthyroidism does not often arise for the first timeinearlypregnancy,butcliniciansneedtobeawareof the symptoms and signs (box 2).
How does hyperthyroidism affect pregnancy?
Pregnancy outcome
Pre-eclampsia, heart failure, fetal loss, prematurelabour, and having a low birthweight baby are morelikely to occur in untreated or poorly controlledthyrotoxic women than in those receiving adequatetreatment.
A retrospective review of 11 reportsdocumenteda5.6%incidenceoffetaldeathorstillbirthin 249 pregnancies and a further 5% incidence of fetaland neonatal abnormalities.
A study of 60 cases of hyperthyroidism in pregnancy over a 12 year periodfound that metabolic status at delivery correlated withpregnancy outcome.
Preterm delivery, perinatalmortality, and maternal heart failure were morecommon in women who remained thyrotoxic despitetreatment or whose hyperthyroidism was first diag-nosed during pregnancy.Women with thyroid hormone resistance (wherethyroid hormone andthyrotrophinconcentrations areinappropriately high
that is, not due to autoimmu-nity) also have a high miscarriage rate, indicating a direct toxic effect of thyroid hormones on the fetus.
Fetal and neonatal thyroid dysfunction
Improvement of Graves
hyperthyroidismduring woman
s pregnancy is often associated with a reduc-tion in the titre of maternal serum TRAb concentra-tions and a change from stimulatory to blocking antibodies. If antibodies do not decline they will crossthe placenta and stimulate the fetal thyroid, evidencedby signs of fetal hyperthyroidism such as tachycardia,intrauterinegrowthretardation,cardiacfailure,andthedevelopment of fetal goitre.One to five per cent of neonates of mothers withGraves
disease have hyperthyroidism as a result of the transplacental passage of maternal TRAbconcentrations.
Presentation of neonatal hyper-thyroidism may be delayed as antithyroid drugsadministered to the mother are cleared more rapidly
Thisisoneofaseriesofoccasionalarticles about how to manage apre-existing medical conditionduring pregnancy.
diseaseTransient gestational hyperthyroidismToxic multinodular goitreSingle toxic adenomaSubacute thyroiditisTrophoblastic tumour Iodide induced hyperthyroidismStruma ovariiThyrotrophin receptor activation
Department of Obstetrics,University Hospital of Wales,Cardiff CF14 4XN
Centre for Endocrine andDiabetes Sciences, UniversityHospital of Wales, Cardiff 
Correspondence to: J H Lazaruslazarus@cf.ac.uk
BMJ 2008;336:663-7
22 MARCH 2008
For the full versions of these articles see bmj.com
 on 30 March 2008bmj.comDownloaded from 
from the fetal circulation than maternal stimulating antibodies.Maternal euthyroidism is particularly important inthe later stages of pregnancy, as poorly controlledhyperthyroidism can lead to suppression of the fetalpituitary thyroid axis resulting from placental transferof thyroxine. A case-control study noted a low thyrotrophin concentration, a blunted result (that is,suppressedcomparedwiththenormalresponse)witha thyrotrophin releasing hormone test, and low serumthyroxine concentration in a group of neonates whosemothershadhadpoorlycontrolledhyperthyroidisminthe third trimester of pregnancy. The condition maylast up to six months, as described in two case series.
Subclinical hyperthyroidism has no known associatedadverse pregnancy outcomes.
How does pregnancy affect hyperthyroidism?
A deterioration in previously diagnosed thyroiddisease is not uncommon during the first trimester of pregnancyandmaybeduetoanincreaseinthetitreof TRAb concentrations or high levels of human chor-ionic gonadotrophin acting as a thyroid stimulator.Relapsemayalsobecausedbyimpairedabsorptionof antithyroid medication secondary to vomiting that isassociatedwithpregnancyorbyreluctancetocontinuemedication in the first trimester.
Human immune regulation involves homoeostasisbetweenThelper1(Th1)andThelper2(Th2)activity,with Th1cells drivingcellular immunityandTh2 cellshumoralimmunity.Theimmunestatusofpregnancyisa Th2 state, which allows tolerance of the fetus during pregnancy,andthisisthoughttobethereasonwhytheseverity of Graves
hyperthyroidism (and otherautoimmune diseases) usually lessens after the first trimester.
Hyperthyroidism before pregnancy may remiduring pregnancy but will recur in the postpartumperiod as the immune status reverts to a Th1 state.On rare occasions, labour, caesarean section, andinfections may aggravate hyperthyroidism to theextent that cases of thyroid storm (a life threatening form of hyperthyroidism) have been observed.
How is hyperthyroidism treated in pregnancy?
Prepregnancy planning and counselling
Ideally,awomanwhoknowsshehashyperthyroidismshould seek prepregnancy advice, although no evi-dence exists yet for the benefit of this.
Patients already treated for hyperthyroidism caused byGraves
Although patients who have already been treated forhyperthyroidismmayhavereceivedantithyroiddrugs,had surgery, or had radioiodine therapy and beeuthyroid (whether receiving thyroxine or not),neonatal hyperthyroidism may still occur. TRAbconcentration should be measured early in pregnancyin a euthyroid pregnant women who has previouslyhadsurgeryor radioiodine therapy.
If the concentra-tion is high at this time, the fetus should be evaluatedcarefullyduringgestation(withserialultrasonography)and the antibodies measured again in the thirdtrimester. If the TRAb concentration is high at 36 weeks, the neonate needs to be checked forhyperthyroidism after delivery.
Treatment of hyperthyroidism in pregnancy
Box 3 outlines the main elements in managing hyperthyroidism in a pregnant woman. At all stagesof pregnancy antithyroid drugs are the preferredtreatment (table).
Radioiodine is contraindicated(box 4) and surgery requires pretreatment with anti-thyroid drugs to render the patient euthyroid.The thionamides carbimazole, methimazole (themetabolite of carbimazole), and propylthiouracil areall effective in inhibiting thyroidal biosynthesis of thyroxine during pregnancy. Propylthiouracil is thepreferred drug in pregnancy as carbimazole andmethimazole are (albeit rarely) associated with terato-genic effects.An early study also reported less placental transferof propylthiouracil than of methimazole, but results of a more recent study measuring propylthiouraciland methimazole concentrations and examining placental perfusion in vitro have not shown anyadvantage for propylthiouracil in relation to placentaltransport.Furthermore,thetwodrugsseemtohavenodifference in effect on fetal and neonatal thyroidfunction.This use of propylthiouracil as the initial preferreddrug for maternal hyperthyroidism is an expert consensus recommendation of the EndocrineSociety.
In countries where propylthiouracil isnot available, carbimazole and methimazole are
Mostpregnantwomenwithhyperthyroidismareknowntohavehadthyroiddiseasebeforethe onsetof gestation and will alreadybe receiving treatment. Anewdiagnosisof hyperthyroidismisuncommoninearlypregnancy,asuntreateddiseaseisassociatedwithreducedfertility.However,inaseriesof14970firsttrimesterbloodsamples,undiagnosedGraves
hyperthyroidismwaspresentin about0.15%.
Featuressuch astachycardia,palpitations, systolicmurmur,bowel disturbance, emotional upset, and heatintolerancemaybe seen in normal pregnancybut shouldalertthe clinician tothe possibilityof hyperthyroidism,particularlyifa goitreormorespecificfeatureof thyroid disease(weightloss, eye signs,tremor or pre-tibialmyxoedema)isobserved. Newlydiagnosedhyperthyroidismshould be aggressivelytreated.
Drug Mode of action Dose Adverse effects
Propylthiouracil Inhibitsthyroxinesynthesis;inhibitsperipheralconversion ofthyroxine totriiodothyronineStarting: 300-450 mg/day;maintenance: 50-100 mg/dayRash, fever, agranulocytosisCarbimazole Inhibitsthyroxinesynthesis Starting: 15-40mg/day;maintenance: 5-15 mg/dayAsabove, plusaplasiacutisand methimazoleembryopathyPropranolol Reduces adrenergicsymptoms10-40 mg,3-4 times/day(short termuse only)Bronchospasm, intrauterinegrowthrestriction, neonatalhypoglycaemia
22 MARCH 2008
 on 30 March 2008bmj.comDownloaded from 

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