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2016AmericanThyroidAssociationHyperthyroidismGuidelines:
What’sNew?MerckThyr0idSymposiumApril22-23,2017Dalian,ChinaRebeccaBahnMDProfessorofMedicineMayoCliniccollegeofMedicineRochester,MNThyroid:21,593;2011Thyroid:25,1343;2016What’snewintheguidelines?ExpandeduseofTRAbmeasurementsInformationconcerningATDhepatotoxicityandsafetyoflong-termuseModifiedmanagementofGDbeforeandduringpregnancyOptimizationofcalciumandvitaminDmetabolismpriortothyroidectomyStillatthecoreofoptimummanagement:
Patient-centricdecisionmaking
“Oncethediagnosishasbeenmade,thetreatingphysicianandpatientshoulddiscusseachofthetreatmentoptions,includingthelogistics,benefits,expectedspeedofrecovery,drawbacks,potentialsideeffectsandcost.Thissetsthestageforthephysiciantomakerecommendationsbasedonbestclinicaljudgment
andallowsthefinaldecisiontoincorporatethepersonalvaluesandpreferencesofthepatient.”
AdvantagesDisadvantagesAntithyroiddrugs
avoidlife-longLT4replacementavoidradiationexposureavoidrisksofsurgerypossibledrugreactionnotdefinitivetherapyRadioiodinedefinitivetherapyavoidrisksofsurgeryavoidadversedrugreactionradiationexposurelife-longLT4replacementpossibleGOworseningThyroidectomyrapidresolutionavoidradiationexposureavoidadversedrugreactionpossibleGOimprovementsurgicalrisk(hypoparathyroidism,recurrentlaryngealnervedamage)life-longLT4replacementAdvantagesandDisadvantagesofTreatmentoptionsforGDBahnetal.Thyroid:21,593;2011ToolforSharedDecisionMakingAbouttheTreatmentofGraves'Disease.BritoJPetal.Thyroid25(11):1191,2015UseofTRAbmeasurementsin:DiagnosisofGDDiscontinuingATDtherapyAssessingriskoffetal/neonatalGD2011:AradioactiveiodineuptakeshouldbeperformedwhentheclinicalpresentationofthyrotoxicosisisnotdiagnosticofGraves’disease.Athyroidscanshouldbeaddedinthepresenceofthyroidnodularity.
2016:Ifthediagnosisisnotapparentbasedontheclinicalpresentationandinitialbiochemicalevaluation,diagnostictestingisindicatedandcaninclude,dependingonavailableexpertiseandresources,(1)measurementofTRAb,(2)determinationoftheradioactiveiodineuptake,or(3)measurementofthyroidalbloodflowonultrasonography.123Ior99mTcpertechnetatescanshouldbeobtainedwhentheclinicalpresentationsuggeststoxicadenomaortoxicmultinodulargoiter.TSIAssayUtilization:ImpactonCostsofGraves’
HyperthyroidismDiagnosis
McKeeA,PeyerlF.AmJManagedCare.2012;18(1):e1-e14Anevidence-basedeconomicmodelwasdevelopedinapopulationof100,000managedcareenrollees.InclusionofaTSItestearlyinthediagnosticpathwayresultedin:Netdirectcostsofdiagnosisreducedby43%.Netcostofavoidingmisdiagnosisandtreatmentofunexplainedsymptomsreducedby85%.Overallnetcostandtimetodiagnosiswerebothreducedby50%TheuseofcolordopplerUStomeasurethyroidbloodflowanddifferentiateGDfrompainlessthyroiditis
HiraiwaT,etal.EurThyroidJ2013;2:2120Superiorthyroidarterybloodflowvelocitysensitivity=0.87specificity=1.00.Thyroidtissuebloodflowsensitivity=0.71specificity=1.00.UseofTRAbindecisiontodiscontinueATDtherapy 2011IfmethimazoleischosenastheprimarytherapyforGD,themedicationshouldbecontinuedforapproximately12–18months,thentaperedordiscontinuediftheTSHisnormalatthattime.MeasurementofTRAblevelspriortostoppinganti-thyroiddrugtherapyissuggested…..
2016IfMMIischosenastheprimarytherapyforGD,themedicationshouldbecontinuedforapproximately12–18months,thendiscontinuediftheTSHandTRAblevelsarenormalatthattime.TRAbpositiveafter18monthsMMIRx=89%relapserateTRAbnegativeafter18mosMMIRx=29%relapserateLaurbergPetal.EurJEndocrinol2008;158:69-752011:PatientsfoundtohaveGDduringpregnancy(orwhoweretreatedwithRAIorthyroidectomyforGDpriortopregnancy)shouldhaveTRAblevelsmeasuredatdiagnosisusingasensitiveassayand,ifelevated,againat22–26weeksofgestation.
2016:PatientsreceivingATDforGDwhenbecomingpregnant(orwhoweretreatedwithRAIorthyroidectomyforGDpriortopregnancy)orfoundtohaveGDduringpregnancyshouldhaveTRAblevelsmeasuredatinitialpregnancyvisitoratdiagnosisusingasensitiveassayand,iftheyareelevated,againat18–22weeksofgestation.UseofTRAbinassessingriskoffetal/neonatalGD
EarlySevereFetalGravesDiseaseinaMotherafterThyroidAblationandThyroidectomy
DonnellyMAetal.ObstetGynecol2015;125:1059–6236-year-oldwomanwithhistoryofsevereGD,radioiodineablationandthyroidectomyUSat18weeksshowedfetustobeseverelytachycardicwithagoiter.MaternalTSIandTRAbwere“toohightomeasure”P.H.BisschopPH,vanTrotsenburgASP.NEJM370;13,2014NewinformationconcerningATDhepatotoxicity2016:LiverfunctionandhepatocellularintegrityshouldbeassessedinpatientstakingMMIorPTUwhoexperiencepruriticrash,jaundice,light-coloredstoolordarkurine,jointpain,abdominalpainorbloating,anorexia,nausea,orfatigue.2011:LiverfunctionandhepatocellularintegrityshouldbeassessedinpatientstakingPTUwhoexperiencepruriticrash,jaundice,light-coloredstoolordarkurine,jointpain,abdominalpainorbloating,anorexia,nausea,orfatigue.Antithyroiddrug‐relatedhepatotoxicityinhyperthyroidpatients:
apopulation‐basedcohortstudy
WangM-T,LeeW-J,HuangT-Y,ChuC-L,Hsieh,C-H.BJClinPharm78:(3)619-629,201471,379newusersofATDslistedinTaiwanNationalHealthInsuranceDatabaseMMIwasassociatedwithasignificantlyhigherrateofnoninfectioushepatitisthanPTU(0.25%vs.0.08%)PTUwasassociatedwithasignificantlyhigherrateofacuteliverfailurethanMMI(0.048%vs.0.026%)Nodifferenceonrateofcholestasis(0.019%vs.0.016%)Antithyroiddrug‐relatedhepatotoxicityinhyperthyroidpatients:
apopulation‐basedcohortstudy
WangM-T,LeeW-J,HuangT-Y,ChuC-L,Hsieh,C-H.BJClinPharm78:3,619-629
highdosePTUhazardratioSafetyoflong-termATDuse2011and2016:IfapatientwithGDbecomeshyperthyroidaftercompletingacourseofMMI,considerationshouldbegiventotreatmentwithRAIorthyroidectomy.Continuedlow-doseMMItreatmentforlongerthan12–18monthsmaybeconsideredinpatientsnotinremissionwhopreferthisapproach.However,newdatasupportsafetyoflong-termATDuseAntithyroidDrugSideEffectsinthePopulation
AndersenSL,OlsenJ,LaurbergP.JClinEndocrinolMetab2016;101(4):1606-1614.Durationoftreatmentuptotheevent(days)28,998patients:Most(83%)developedthesideeffectwithin3monthsofATDinitiationorre-initiationafterrelapseAnalysisof90casesofATD-inducedseverehepatotoxicityover13yearsinChina
YangJetal.Thyroid25(3);278,2015Hepatotoxicityoccurredwithin12weeksofstartingATDtherapyin80%ofpatients.SeverehepatotoxicitydidnotdifferbetweenMMIandPTU(p=0.188).Frequencyofcholestatichepatotoxicitydidnotdiffer(p=0.069).Analysisof754CasesofAntithyroidDrug-InducedAgranulocytosisOver30YearsinJapan
NakamuraH,etal.ClinEndocrinolMetab98:4776–4783,2013ModifiedmanagementofGDbeforeandduringpregnancy2016:WomenwithGDthatiswellcontrolledonMMIandwhodesirepregnancyhaveseveraloptions:Patientscouldconsiderde?nitivetherapybeforetheybecomepregnant.PatientscouldswitchtoPTUbeforetryingtoconceive.PatientscouldswitchtoPTUassoonaspregnancyisdiagnosed.AppropriatelyselectedpatientscouldwithdrawfromATDtherapyassoonaspregnancyisdiagnosed.IfATDtherapyiswithdrawn,thyroidfunctionshouldbeassessedweeklythroughoutthe?rsttrimester,thenmonthly.2011:WesuggestthatpatientstakingMMIwhodecidetobecomepregnantobtainpregnancytestingattheearliestsuggestionofpregnancyandbeswitchedtoPTUassoonaspossibleinthefirsttrimester.
2016:WomentakingPTUduringthe?rsttrimesterofpregnancymaybeswitchedtoMMIatthebeginningofthesecondtrimester,ortheymaycontinuePTUtherapyfortheremainingpartofpregnancyifATDisneeded.Norecommendation;insuf?cientevidencetoassessbene?tsandrisks.2011:
WesuggestthatwomentakingPTUduringthe?rsttrimesterofpregnancybechangedbacktoMMIatthebeginningofthesecondtrimester.Similarly,wesuggestthatpatientsstartedonPTUduringthefirsttrimesterbeswitchedtoMMIatthebeginningofthesecondtrimester.Weakrecommendation;poorqualityevidence BirthDefectsAfterEarlyPregnancyUseofAntithyroidDrugs:ADanishNationwideStudyAndersenS,OlsenJ,WuHenSen,LaurbergP.JClinEndocrinolMetab98:4373,2013BothMMI/CMZwereassociatedwithbirthdefects,butthespectrumofmalformationsdiffered.Prevalenceofbirthdefectswashigh:PTU=8.0%;OR=1.03MMI/CMZ=9.1%;OR=1.66PTU+MMI/CMZ=10.1%;OR=1.82Notexposed=5.7%OptimizationofcalciumandvitaminDmetabolismpriortothyroidectomyNewin2016Calciumand25-hydroxyvitaminDshouldbeassessedpreoperativelyandrepletedifnecessary,orgivenprophylactically.Calcitriolsupplementationshouldbeconsideredpreoperativelyinpatientsatincreasedriskfortransientorpermanenthypoparathyroidism.Preventingpostoperativehypocalcemia
inpatientswithGraves’disease
OltmannSCetal.2015AnnSurgOncol22:952–958GDpatients(n=45)given1.0gofcalciumcarbonate(CC)threetimesadayfor2weeksbeforetotalthyroidectomy(TT);HistoriccontrolswithGD(n=38)orotherindicationforTT(n=40)PostoperativecalciumlevelsGDw/oCCpre-treatment(8.3mg/dL)vs.GDwithCCorControlw/oGDorCC(both8.6mg/dL;p=0.05)PostoperativenumbnessandtinglingGDw/oCC(26%)vs.GDwithCC(9%)orControlw/oGDorCC(10%;p<0.05)Meta-analysisofpredictors
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