201767 Graves'hyperthyroidisminnonpregnantadults:OverviewoftreatmentUpToDate

Author: DouglasSRoss,MD
SectionEditor: DavidSCooper,MD
DeputyEditor: JeanEMulder,MD

ContributorDisclosures

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:May2017.|Thistopiclastupdated:Sep22,2016.

INTRODUCTIONGraves'diseaseisanautoimmunediseasethatmayconsistofhyperthyroidism,goiter,
eyedisease(orbitopathy),andoccasionallyadermopathyreferredtoaspretibialorlocalizedmyxedema.
HyperthyroidismisthemostcommonfeatureofGraves'disease,affectingnearlyallpatients,andiscaused
bythyroidstimulatinghormone(TSH,thyrotropin)receptorantibodies(TRAb)thatactivatethereceptor,
therebystimulatingthyroidhormonesynthesisandsecretionaswellasthyroidgrowth(causingadiffuse
goiter).ThepresenceofTRAbinserumandorbitopathyonclinicalexaminationdistinguishthedisorderfrom
othercausesofhyperthyroidism.

ThistopicwillprovideanoverviewoftreatmentoptionsforGraves'hyperthyroidisminnonpregnantadults.
ThepathogenesisofGraves'disease,theclinicalmanifestationsanddiagnosisofhyperthyroidism,other
causesofanoveractivethyroidgland,aswellastreatmentofGraves'diseaseinpregnantwomenand
childrenarereviewedinmoredetailinseparatetopicreviews.Thetreatmentofhyperthyroidismduetoother
etiologiesisreviewedintheindividualtopics.

(See"PathogenesisofGraves'disease".)
(See"Overviewoftheclinicalmanifestationsofhyperthyroidisminadults".)
(See"Diagnosisofhyperthyroidism".)
(See"Disordersthatcausehyperthyroidism".)
(See"Hyperthyroidismduringpregnancy:Treatment".)
(See"TreatmentandprognosisofGraves'diseaseinchildrenandadolescents".)

THERAPEUTICAPPROACHThetherapeuticapproachtoGraves'hyperthyroidismconsistsofbothrapid
ameliorationofsymptomswithabetablockerandmeasuresaimedatdecreasingthyroidhormonesynthesis:
theadministrationofathionamide,radioiodineablation,orsurgery[1].

TheapproachoutlinedbelowisconsistentwithHyperthyroidismManagementGuidelinesfromtheAmerican
ThyroidAssociation(ATA)[2].

SymptomcontrolAbetablockershouldbestarted(assumingtherearenocontraindicationstoitsuse)in
mostpatientsassoonasthediagnosisofhyperthyroidismismade,evenbeforeconfirmingthatthecauseof
hyperthyroidismisGraves'disease.Weusuallygiveatenolol(25to50mg/day),whichhastheadvantagesof
singledailydosingandbeta1selectivityhowever,allbetaadrenergicblockingdrugseffectivelydiminish
hyperthyroidsymptoms.Betablockersamelioratethesymptomsofhyperthyroidismthatarecausedby
increasedbetaadrenergictone[3].Theseincludepalpitations,tachycardia,tremulousness,anxiety,andheat
intolerance.Fatigabilityandshortnessofbreathwerealsoimprovedinpatientswhoweretreatedwithabeta
blockerandathionamideversusathionamidealone[4].(See"Betablockersinthetreatmentof
hyperthyroidism".)

Decreasethyroidhormonesynthesis

TreatmentoptionsTherearethreetreatmentoptionsforGraves'disease:antithyroiddrugs
(thionamides),radioiodine,orsurgery.Allthreeoptionsareeffective,butallthreeoptionshavesignificant

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sideeffects(table1).Becausethereisnoconsensusastothe"best"treatment,theATAguidelines
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201767 Graves'hyperthyroidisminnonpregnantadults:OverviewoftreatmentUpToDate

emphasizetheimportanceoffullydiscussingtheoptionswithpatientsandconsideringtheirvaluesand
preferencesbeforedecidingonatreatmentplan[2,5].

Additionally,thethreeoptionsarenotmutuallyexclusive.Antithyroiddrugsmaybeusedinitiallytocontrol
hyperthyroidismpriortodefinitivetherapywithradioiodineorsurgery,theymaybeprescribedforonetotwo
yearstotryandattainaremission,ortheymaybeusedlongterm.Radioiodinemaybegivenasinitial
therapyorafterpretreatmentwithantithyroiddrugs,andsurgeryisusuallyprecededbyantithyroiddrugsto
attainaeuthyroidstatepreoperatively.

Therearefewtrialscomparingtherapies[6].Intheonlyrandomizedtrialcomparingallthreetherapies,each

wasequallyeffectiveinnormalizingserumthyroidhormoneconcentrationswithinsixweeksaftertreatment,
95percentormoreofthepatientsweresatisfiedwiththeirtherapy[7,8].Inaddition,mostpatientsreported
thattheywouldrecommendthetherapytoafriendwithoutreservation(medical:68percentsurgical:74
percentradioiodine:84percent).Theriskofrelapsewas37,21,and6percentinthethionamide,
radioiodine,andsurgerygroups,respectively.

ChoiceoftherapyForpatientswithsignificantsymptomsofhyperthyroidism,orpatientswitha
significantriskofhyperthyroidcomplications(eg,olderage,cardiovasculardisease),wesuggeststartinga
thionamide(inadditiontobetablockers)toachieveeuthyroidismquickly.Thiscanbefollowedbyablative
therapywithradioiodineorsurgery,bycontinuationofathionamideforonetotwoyearswiththehopeof
attainingaremission,orbymoreprolongedtreatmentwithathionamide.

Radioiodinecanbeusedasinitialtherapy(withoutthionamidepretreatment)inpatientswhoaretolerating
hyperthyroidsymptomsandwhoarenotatriskforcomplications.

Individualpatientfactorsmayinfluencethechoiceoftherapy:

Forpatientswithmildhyperthyroidism,minimalthyroidenlargement,andnoorbitopathy,radioiodine
(withoutthionamidepretreatmentorglucocorticoids)oraonetotwoyearcourseofthionamidesare
goodoptions.

Forpatientswithmildhyperthyroidism,minimalthyroidenlargement,andmildorbitopathy,radioiodine
(withglucocorticoidcoveragebutwithoutthionamidepretreatment)oraonetotwoyearcourseof
thionamidesaregoodoptions.

Forpatientswithmoreseverehyperthyroidism,wesuggestdefinitivetherapywithradioiodineorsurgery,
butaonetotwoyearcourseofthionamidesorlongtermthionamidetherapyarebothreasonable
alternatives.

Forpatientswithmoderatetosevereorbitopathy,weprefersurgeryratherthanradioiodinewith
glucocorticoidcoveragefordefinitivetherapy.

Radioiodineiscontraindicatedduringpregnancyandlactationandshouldbediscouragedorprohibited
inpatientswhocannotfollowradiationprecautions(eg,solecaregiversforinfantsoryoungchildren,or
incontinentolderadultpatients).

Surgerymaybethebestoptionforpatientswithlargegoitersandpatientswithsuspiciousnodulesor
hyperparathyroidismbutmaybeapooroptionforpatientswhoareolder,athighsurgicalrisk,orwithout
accesstohighvolumethyroidsurgeons.

Antithyroiddrugsarecontraindicatedinpatientswithprioradversereactions(agranulocytosisor
hepatitis).Becausetheyareteratogenic,theirlongtermuseinwomendesiringapregnancyinthenext
yearortworequiresacarefuldiscussionoftheirrisksandalternativetreatments,suchasdefinitive
therapypriortoconception.Theirlongtermusemaybepreferredinolderadultpatientswith

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contraindicationstosurgeryandradioiodineorinpatientswhowanttoavoiddefinitivetherapy.
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201767 Graves'hyperthyroidisminnonpregnantadults:OverviewoftreatmentUpToDate

OverhalfofcliniciansintheUnitedStatesstillpreferradioiodinewhileapproximately40percentwillbegin
withaonetotwoyearcourseofantithyroiddrugs.Incontrast,radioiodineisunpopularinEuropeandAsia,
withover80percentofEuropeanclinicianschoosingantithyroiddrugsandonly14percentchoosing
radioiodine[9].ThepopularityofantithyroiddrugsmaybeincreasingintheUnitedStates[10].Thechoiceof
therapyshouldinvolvethevaluesandpreferencesofthepatient.

Theindividualtherapiesarediscussedbrieflybelowandinmoredetailintheindividualtopicreviews.

ThionamidesForpatientswithsignificantsymptomsofhyperthyroidism,wesuggeststartinga

thionamide(inadditiontobetablockers)toachieveeuthyroidismrelativelyquickly,priortomoredefinitive

therapywithradioiodineorsurgery.ThegoalofthionamidetherapyinGraves'hyperthyroidismistoattaina
euthyroidstatewithinthreetoeightweeks.Thiscanbefollowedbyablativetherapywithradioiodineor
surgery,bycontinuationofthedrugforonetotwoyearswiththehopeofattainingaremission,orforlong
termtherapy.

Antithyroiddrugswillcontrolhyperthyroidisminmostpatientsaslongasthedrugistaken,butremission
rates(thepercentageofpatientswhoremaineuthyroidoneyearafterthedrugiswithdrawn)averageunder
40percent[7].Remissionismorelikelyinpatientswithmildhyperthyroidismandpatientswithsmallgoitersor
withgoitersthatshrinkduringthionamidetherapy.Thus,primaryantithyroiddrugtherapymaybepreferred
forpatientswithmilddiseaseandsmallgoiters,whoaremorelikelytoachieveremissionafteroneyearof
treatment.(See"ThionamidesinthetreatmentofGraves'disease",sectionon'Predictorsofremission'.)

PretreatmentevaluationPriortoinitiatingthionamides,weobtainbaselinebloodtests,includinga
completebloodcount(whitecountwithdifferential)andaliverprofile(bilirubinandtransaminases)[2].
Wedonotusethionamidesinpatientswithabaselineabsoluteneutrophilcount<1000cells/microLor
elevatedlivertransaminases(morethanfivefoldtheupperlimitofnormal)exceptinselectedpatients
aftercarefulassessmentofalternativesandrisks.(See"ThionamidesinthetreatmentofGraves'
disease",sectionon'Initiationoftherapy'.)

ChoiceofthionamideThethionamidemethimazoleistheprimarydrugusedtotreatGraves'
hyperthyroidism[2].Methimazoleisnowalmostexclusivelyusedbecauseofitslongerdurationofaction,
allowingforoncedailydosing,morerapidefficacy(figure1),andlowerincidenceofsideeffects.
Propylthiouracil(PTU)ispreferredduringthefirsttrimesterofpregnancy,becauseofthemore
significantteratogeniceffectsofmethimazole,andinpatientswhohaveminordrugreactionsto
methimazolewhorefuseradioiodineorsurgery.(See"Pharmacologyandtoxicityofthionamides".)

Incountrieswheremethimazoleisunavailable,carbimazolecanbeused.Itismetabolizedto
methimazole,andthedoserequiredtoyieldasimilardoseofmethimazoleisapproximately40percent
higher.Forexample,a10or20mgdoseofcarbimazoleyieldsroughly6and15mgofmethimazole,
respectively.

DosingThestartingdoseofmethimazolevariesaccordingtotheseverityofthehyperthyroidism.(See
"ThionamidesinthetreatmentofGraves'disease",sectionon'Dosing'.)

Patientswithsmallgoitersandmildhyperthyroidism(freethyroxine[T4]levels1to1.5timesthe
upperlimitofnormal)canbestartedon5to10mgoncedaily.

PatientswithfreeT4levels1.5to2timestheupperlimitofnormalcanbestartedon10to20mg
daily.Thisregimenisaseffectiveashigherdosesinmostcases(figure2),andsideeffectsfrom
methimazolearedoserelated.

Patientswithlargergoitersandmoreseverehyperthyroidism(freeT4levelsapproximately2to3
timestheupperlimitofnormal)shouldbestartedon20to40mgdaily.

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Forpatientstaking20mgdaily,weadministerinitialtherapyindivideddosesforaweekortwo,to
normalizethyroidfunctionmorequicklyandtominimizegastrointestinal(GI)sideeffects,andthen
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201767 Graves'hyperthyroidisminnonpregnantadults:OverviewoftreatmentUpToDate

changetosingledailydosing.

Iflongtermmedicaltherapyischosen,thedoseofmethimazoleisthentaperedtoamaintenancedose
withthegoalofmaintainingaeuthyroidstate.

Thereareseveralotherissuesrelatedtothionamidetherapy,includingcontraindications,monitoring,
managementofcomplications,theprevalenceofpermanentremissionaftercessationoftherapy,thetime
courseofrelapse,anditsnegativeeffectonsubsequentradioactiveiodinetherapy.(See"Thionamidesinthe
treatmentofGraves'disease"and"Pharmacologyandtoxicityofthionamides",sectionon'Toxicitiesandtheir

management'.)

RadioiodineablationRadioiodineislessexpensiveandhasalowercomplicationratethansurgery
andispreferredasdefinitivetherapyofhyperthyroidisminnonpregnantpatientsexceptinpatientswith
moderateorsevereorbitopathy.Forpatientswithsignificantsymptomsofhyperthyroidism,whoareolder,or
whohaveunderlyingheartdiseaseorothercomorbidities,wetreatwithathionamide(inadditiontobeta
blockers)torestoreeuthyroidismpriortoradioiodinetreatment.Forpatientswithmild,welltolerated
hyperthyroidism,thereisnoneedtopretreatwithathionamide,andradioiodinecanbegivensoonafterthe
diagnosisismade.(See"Radioiodineinthetreatmentofhyperthyroidism",sectionon'Pretreatmentwith
methimazole'.)

Ifradioiodineischosen,thepatientmustbecomfortablewiththedecisiontoablatethethyroidandbeaware
thatprolongedthionamidetherapylastingevendecadesisanacceptablealternativeaslongasthedrugis
toleratedandthehyperthyroidismiscontrolled[11].Cliniciansandpatientsmustalsobeawarethatthereis
increasingevidencethatradioiodinetherapycancausethedevelopmentorworseningofGraves'orbitopathy
moreoftenthanantithyroiddrugtherapyorsurgery.Thechangesareoftenmildandtransient,atleastin
patientswhohavemildornoorbitopathybeforetherapy.TheATAguidelinesdonotrecommendradioiodine
forpatientswithmoderatetosevereorbitopathy[2],butradioiodinewithglucocorticoidcoverageisapossible
optionforsuchpatientswhorefusesurgeryandhavecontraindicationstoantithyroiddrugs.(See
"Radioiodineinthetreatmentofhyperthyroidism",sectionon'Moderatetosevereorbitopathy'and
"Radioiodineinthetreatmentofhyperthyroidism",sectionon'Radioiodineandorbitopathy'.)

Radioiodineisadministeredasacapsuleor,lesscommonly,anoralsolutionofsodiumI131,whichisrapidly
absorbedfromtheGItractandconcentratedinthyroidtissue.Radioiodineinducesextensivetissuedamage,
resultinginablationofthethyroidwithin6to18weeks[12].Approximately10to20percentofpatientsfailthe
firstradioiodinetreatmentandrequireasecondorsubsequentdose.Thesepatientsusuallyhavemore
severehyperthyroidismorlargergoiters.Adiscussionondosingandsideeffects,includinghypothyroidism,
canbefoundelsewhere.(See"Radioiodineinthetreatmentofhyperthyroidism",sectionon'Monitoring'and
"Radioiodineinthetreatmentofhyperthyroidism",sectionon'Adverseeffects'.)

SurgeryForapatientwithseverehyperthyroidismandalargegoiter,wesuggestsurgery.Itisalso
indicatedforpatientswhoareallergictothionamidesandareunabletoordonotwanttoreceiveradioiodine.
(See"Surgicalmanagementofhyperthyroidism".)

SurgeryisanunpopulartherapyforGraves'hyperthyroidism,beingselectedbyonly1percentofthyroid
specialists[9],butisbeingusedmorefrequentlyinpatientswithactiveorbitopathy[13].Itisprimarily
indicatedinpatientswhohaveanobstructivegoiteroraverylargegoiterinpatientswithmoderateto
severe,activeorbitopathywhodesiredefinitivetherapyfortheirhyperthyroidisminpregnantwomenwhoare
allergictoantithyroiddrugsandinpatientswhohaveallergiesorpoorcomplianceonantithyroiddrugsbut
refuseradioiodine.Surgerywouldalsobeindicatediftherewasacoexistingsuspiciousormalignantthyroid
noduleorprimaryhyperparathyroidism.However,mostthyroidnodulesassociatedwithGraves'diseaseare
benign,inwhichcasesurgerywouldnotberecommended[14].Patientswhofearradioactivityorhavehad
anadverseeffectwiththionamidedrugsmayalsoprefersurgery.

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Preoperativepreparationforpatientswithhyperthyroidismisreviewedindetailseparately.(See"Surgical
URL,DOI,
managementofhyperthyroidism",sectionon'Preoperativepreparation'.)
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PregnancyWeadvisewomendesiringtobecomepregnantinthenearfuturetoconsiderradioiodineor
surgerysixmonthsinadvanceofaplannedpregnancy,toavoidtheneedforathionamideduringthe
pregnancy.However,ifradioiodineorsurgeryisnotdesired,PTUtherapywouldbethepreferreddrugduring
thefirsttrimesterofpregnancy.Thetreatmentofhyperthyroidismduringpregnancyisreviewedseparately.
(See"Hyperthyroidismduringpregnancy:Treatment".)

AdjunctivetherapiesPatientswhohaveseverehyperthyroidismorareallergictothionamidesmay
benefitfromalternativemedicaltherapies.Werarelyusetheseadjunctivetherapieswiththeexceptionof
iodine,whichweuseforpreoperativepreparationforthyroidectomyinGraves'disease,forthetreatmentof

severehyperthyroidismorthyroidstorm,orlesscommonly,afteradministrationofradioiodineorwith
antithyroiddrugs.(See"Iodineinthetreatmentofhyperthyroidism",sectionon'Indications'.)

IodinatedcontrastagentsandiodineTheoralradiocontrastagentssodiumipodateandiopanoic
acidarepotentinhibitorsoftheperipheralconversionofT4totriiodothyronine(T3).Theyarenotusedas
primarytherapybecauseofpossibleinductionofresistanthyperthyroidism.However,whengiven(atdosesof
500to1000mg/day)incombinationwithmethimazole,theycanrapidlyameliorateseverehyperthyroidism
andcanalsobeusedtoprepareahyperthyroidpatientforearlysurgery.However,thesedrugsarenot
currentlyavailableintheUnitedStates.(See"Iodinatedradiocontrastagentsinthetreatmentof
hyperthyroidism".)

Iodineelixirs,upto10dropsofsaturatedsolutionofpotassiumiodide(SSKI,50mgiodideperdrop[0.05
mL])daily,canbeusedtoameliorateverymildhyperthyroidismduetoGraves'disease.Formild
hyperthyroidismthatpersistsafteradoseofradioiodine,smallerdoses(1to2dropsperday)areusually
sufficient.(See"Iodineinthetreatmentofhyperthyroidism".)

OthermedicationsAnumberofothermedicationshavebeenusedinthemanagementof
hyperthyroidism,includingthefollowing:

GlucocorticoidsinhibitperipheralT4toT3conversionand,inpatientswithGraves'hyperthyroidism,
reducethyroidsecretion.Theyhavebeenusedinpatientswithseverehyperthyroidismandthyroid
storm,althoughtheirefficacyisnotwelldemonstrated.(See"Thyroidstorm",sectionon
'Glucocorticoids'.)

Lithiumblocksthyroidhormonerelease,butitsusehasbeenlimitedbyitstoxicity.(See"Lithiumandthe
thyroid".)

Cholestyramine,giveninadoseof4gfourtimesdailywithmethimazole,lowersserumT4andT3
concentrationsmorerapidlythanmethimazolealone[15]andmaybeusefuladjunctivetherapyin
selectedpatientswhorequirerapidameliorationofhyperthyroidsymptoms.

Carnitineisanaturallyoccurringperipheralantagonistofthyroidhormoneactionthathasbeenshownto
amelioratehyperthyroidsymptomsandmayprovetobeusefulclinically[16].

Rituximab,amonoclonalantibodythatcausesperipheralBcelldepletion,mayinduceasustained
remissioninpatientswithGraves'diseaseandlowthyrotropinreceptorantibodies(TRAb)levels,butits
costandsideeffectslimititsutility[17].

InChinaandmanyothercountries,Chineseherbalmedicinesareusedaloneorincombinationwith
antithyroiddrugstotreathyperthyroidism.Theseherbsareclaimedtoweakenthebiologicaleffectsof
T4andinhibitthetransformationofT4toT3.Somearesaidtobeabletomodulatethefunctionof
sympatheticnervesortheimmunesystem.Inasystematicreviewandmetaanalysisof13trialsof1770
participants,theadditionofChineseherbalmedicinestoantithyroiddrugswasbeneficialinsome
patientsforreducingrelapserates,improvingsymptoms,andreducingadverseeffectssuchas

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agranulocytosis[18].However,themethodologicalqualityofthetrialswaspoor,andtheauthors
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URL,DOI,

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201767 Graves'hyperthyroidisminnonpregnantadults:OverviewoftreatmentUpToDate

concludedthattherearecurrentlynowelldesignedtrialstoprovidestrongevidenceforChinese
traditionalherbalmedicineinthetreatmentofhyperthyroidism.

SkeletalhealthOverthyperthyroidismisassociatedwithacceleratedboneremodeling,reducedbone
density,osteoporosis,andanincreaseinfracturerate.Thebonedensitychangesmayormaynotbe
reversiblewiththerapy.Thesechangesinbonemetabolismareassociatedwithnegativecalciumbalance,
hypercalciuria,andrarely,hypercalcemia.Sincehyperthyroidismresultsinanegativecalciumbalance,
reducedbonedensity,andincreasedfracturerisk,patients(withtheexceptionofthosewithhypercalcemia)
shouldbeadvisedtoingest1200to1500mgelementalcalciumdailythroughdietorsupplements.(See
"Bonediseasewithhyperthyroidismandthyroidhormonetherapy"and"CalciumandvitaminD

supplementationinosteoporosis".)

MONITORINGAFTERTREATMENT

ThyroidfunctiontestsWhatevertreatmentisused,initialmonitoringshouldconsistofperiodicclinical
assessmentandmeasurementsofserumfreeT4andoftentotalT3levels.Serumthyroidstimulating
hormone(TSH)concentrationsshouldbeinterpretedwithcautionsincetheymayremainlowforseveral
weeksafterthepatientbecomeseuthyroidandmayevenremainlowtransientlyinpatientswhohavebecome
hypothyroid.

ThionamidesPatientsshouldhavetheirthyroidfunctionassessedatfourtosixweekintervalsuntil
stabilizedonmaintenancethionamidetherapy.PatientswithpersistentlylowserumTSHconcentrations
aftermorethansixmonthsoftherapywithathionamideareunlikelytohavearemissionwhenthedrugis
stopped.Therefore,beforetryingtodiscontinuethethionamide,aplanshouldbeestablishedfor
subsequenttreatmentofrecurrenthyperthyroidism,eitherdefinitivetherapy(radioiodineorsurgery)or
anotheronetotwoyearcourseofathionamide.Patientswithpersistentlyhighlevelsofthyrotropin
receptorantibodies(TRAb,thyroidstimulatingimmunoglobulins[TSI])afteroneormoreyearsof
treatmentarealsounlikelytoremaineuthyroidifthionamidesarediscontinued[19].(See"Thionamides
inthetreatmentofGraves'disease",sectionon'Evaluationpriortostoppingtherapy'.)

RadioiodineForpatientstreatedwithradioiodine,wemeasurefreeT4,totalT3,andTSHfourtosix
weeksaftertreatment,andthenatfourtosixweekintervalsforsixmonths.(See"Radioiodineinthe
treatmentofhyperthyroidism",sectionon'Monitoring'.)

SurgeryForpatientswithGraves'diseasewhoundergoneartotalortotalthyroidectomy,thyroid
hormoneshouldbeinitiatedpriortodischargeinaeuthyroidpatient,andserumTSHshouldbe
measuredsixtoeightweekslatertoadjustthedosetomaintaintheTSHinthenormalreferencerange.

Ifthepatientisstillhyperthyroidatthetimeofsurgery,thyroidhormonereplacementshouldbedelayed
untillevelsfallintothenormalrangetheintervalcanbeestimatedbasedontheweeklonghalflifeof
T4.(See"Surgicalmanagementofhyperthyroidism",sectionon'Hypothyroidism'.)

WeightgainWeightlossisacommonfeatureofhyperthyroidism,andmanypatientsgainconsiderable
weightaftertreatmentoftheirhyperthyroidism[2024].Inthelargeststudyof162hyperthyroidpatients
followedforupto24monthsaftertreatment(radioiodine,athionamide,orsurgery),mean(SE)weightgain
was5.40.5kgandincreaseinbodymassindex(BMI)was81percent[20].

Inthesamereport,preexistingobesity,adiagnosisofGraves'disease,andpriorweightlossindependently
predictedweightgain.Patientswhodevelopedhypothyroidism,eventransiently,gainedthemostweightin
spiteofT4replacement(8.061.42kg).Thisphenomenondoesnotappeartobesimpleregainingof
previouslylostweight,sincethepercentageofoverweight(BMI>25kg/m2)andobese(BMI>30kg/m2)
patientsincreasedfrom38and10percentjustbeforethetreatmentto56and19percentattheendofthe
followupperiod.

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Proposedmechanismsfortheexcessiveweightgaininclude:
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201767 Graves'hyperthyroidisminnonpregnantadults:OverviewoftreatmentUpToDate

Subnormalenergyexpenditureaftertreatment[21]withoutconcomitantreductioninappetiteorfood
intake[22]

Inadequatethyroidhormonereplacement[24]

Patientsshouldbeadvisedaboutthelikelihoodofweightgain,whichmayinpartbepreventedbydietary
advice[25].(See"Obesityinadults:Overviewofmanagement",sectionon'Approachtotherapy'.)

SOCIETYGUIDELINELINKSLinkstosocietyandgovernmentsponsoredguidelinesfromselected
countriesandregionsaroundtheworldareprovidedseparately.(See"Societyguidelinelinks:

Hyperthyroidism".)

INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"
and"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easyto
readmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmore
detailed.Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowant
indepthinformationandarecomfortablewithsomemedicaljargon.

Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremail
thesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsby
searchingon"patientinfo"andthekeyword(s)ofinterest.)

Basicstopics(see"Patienteducation:Hyperthyroidism(overactivethyroid)(TheBasics)")

BeyondtheBasicstopics(see"Patienteducation:Hyperthyroidism(overactivethyroid)(Beyondthe
Basics)"and"Patienteducation:Antithyroiddrugs(BeyondtheBasics)")

SUMMARYANDRECOMMENDATIONS

HyperthyroidismisthemostcommonfeatureofGraves'disease,affectingnearlyallpatients,andis
causedbythyroidstimulatinghormone(TSH,thyrotropin)receptorantibodies(TRAb)thatactivatethe
receptor,therebystimulatingthyroidhormonesynthesisandsecretionaswellasthyroidgrowth(causing
adiffusegoiter).(See'Introduction'aboveand"PathogenesisofGraves'disease".)

ThetherapeuticapproachtoGraves'hyperthyroidismconsistsofbothrapidameliorationofsymptoms
withabetablockerandmeasuresaimedatdecreasingthyroidhormonesynthesiswiththeadministration
ofathionamide,radioiodineablation,orsurgery(table1).Thechoiceoftherapyshouldinvolveactive
discussionbetweenclinicianandpatientitmayalsobedeterminedbytheseverityofthepatient's
hyperthyroidism.(See'Therapeuticapproach'aboveand'Choiceoftherapy'above.)

Assumingtherearenocontraindicationstoitsuse,werecommendusingabetablockerforpatientswith
moderatetoseverehyperadrenergicsymptomsuntileuthyroidismisachievedbythionamides,
radioiodine,orsurgery(Grade1B).(See'Symptomcontrol'aboveand"Betablockersinthetreatment
ofhyperthyroidism".)

Wetypicallystartwithatenolol25to50mgdailyandincreasethedoseasneeded(upto200mgdaily)
toreducepulsetounder90beatsperminuteifbloodpressureallows.

Forpatientswithsignificantsymptomsofhyperthyroidism,orpatientswithasignificantriskof
hyperthyroidcomplications(eg,olderage,cardiovasculardisease),wesuggestathionamideinaddition
tobetablockerstoachieveeuthyroidismquickly(Grade2B).Methimazoleisnowusedalmost
exclusively(exceptduringthefirsttrimesterofpregnancyandinpatientswhohaveminordrugreactions

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tomethimazolewhorefuseradioiodineorsurgery)becauseofitslongerdurationofaction,allowingfor
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oncedailydosing,morerapidefficacy,andlowerincidenceofsideeffects.(See'Choiceoftherapy'
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201767 Graves'hyperthyroidisminnonpregnantadults:OverviewoftreatmentUpToDate

aboveand'Thionamides'aboveand"ThionamidesinthetreatmentofGraves'disease"and
"Pharmacologyandtoxicityofthionamides",sectionon'Toxicitiesandtheirmanagement'.)

Oncepatientswithmoreseverehyperthyroidismareeuthyroidonmethimazole,wesuggestdefinitive
therapywithradioiodineorsurgery(Grade2B).Aonetotwoyearcourseofmethimazoleorlongterm
methimazolearebothreasonablealternatives.(See'Choiceoftherapy'above.)

Intheabsenceofmoderatetosevereorbitopathy,wesuggestradioiodinetherapyifdefinitivetherapyis
desired,givenitslowercostandlowercomplicationratethansurgery(Grade2B).


Forpatientswhoaretoleratinghyperthyroidsymptomsandwhoarenotatriskforcomplicationsfrom
hyperthyroidism,radioiodinecanbeusedasinitialtherapy(withoutantithyroiddrugpretreatment).
Primaryantithyroiddrugtherapyisanalternativeoptionandmaybepreferableforpatientswithmild
diseaseandsmallgoiters,whoaremorelikelytoachievearemissionafterayearoftreatment.(See
'Choiceoftherapy'aboveand"Radioiodineinthetreatmentofhyperthyroidism",sectionon
'Pretreatmentwithmethimazole'.)

Forpatientswithhyperthyroidismduetoaverylargeorobstructivegoiter,wesuggestsurgery(Grade
2C).Itisalsoindicatedforpatientswhoareallergictothionamidesandareunabletoordonotwantto
receiveradioiodine.Surgerymayalsobepreferredinpatientswithactiveorbitopathy.(See'Choiceof
therapy'aboveand"Surgicalmanagementofhyperthyroidism".)

Weadvisewomendesiringtobecomepregnantinthenearfuturetoconsiderradioiodineorsurgerysix
monthsinadvanceofaplannedpregnancytoavoidtheneedforathionamideduringthepregnancy.
However,ifradioiodineorsurgeryisnotdesired,propylthiouracil(PTU)therapywouldbethepreferred
drugduringthefirsttrimesterofpregnancy.(See"Hyperthyroidismduringpregnancy:Treatment".)

Severalconcernsofthepatientalsomayinfluencethechoiceoftherapy.Asanexample,the
recommendationtoavoidclosecontactwithyoungchildrenforseveraldaysafterradioiodine
administrationmaymakethistreatmenttemporarilyunattractiveifalternativechildcareisunavailable.
Patientfearsregardingradiationexposureoragranulocytosisfromthionamidesshouldalsobe
considered.(See"Radioiodineinthetreatmentofhyperthyroidism"and"Pharmacologyandtoxicityof
thionamides".)

Whatevertreatmentisused,initialmonitoringfollowingtreatmentshouldconsistofperiodicclinical
assessmentandmeasurementsofserumfreethyroxine(T4)andtotaltriiodothyronine(T3)levels.
MeasurementofserumTSHcanbemisleadingintheearlyfollowupperiodbecauseitcanremainlow
forweeksorevenmonths,evenwhenthepatientisbiochemicallyeuthyroidorevenhypothyroid,with
serumfreeT4valueswellwithinorevenbelowthenormalrange.(See'Thyroidfunctiontests'above.)

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

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