ThyroidDisorders專業(yè)知識課件

ThyroidDisordersKhalidAl-ShaliMBBS,MSc,FRCP(C),FACPAssistantProfessor,DepartmentofMedicineIntroduction

Thyroiddisorders:HypothyroidismHyperthyroidismandthyrotoxicosisGraves’diseaseThyroiditisToxicadenomaToxicmultinodulargoitreThyrotoxicosisfactitiaStrumaovariiHydatidiformmoleTSH-secretingpituitaryadenomaNontoxicgoitreThyroidnodules&thyroidcancerBenignthyroidnodulesThyroidcancerPapillarycarcinomaFollicularcarcinomaMedullarycarcinomaAnaplasticcarcinomaLymphomaCancermetastatictothethyroidHypothyroidismEtiology:Primary:Hashimoto’sthyroiditiswithorwithoutgoitreRadioactiveiodinetherapyforGraves’diseaseSubtotalthyroidectomyforGraves’diseaseornodulargoitreExcessiveiodineintakeSubacutethyroiditisRarecausesIodidedeficiencyGoitrogenssuchaslithium;antithyroiddrugtherapyInbornerrorsofthyroidhormonesynthesisSecondary:HypopituitarismTertiary:Hypothalamicdysfunction(rare)PeripheralresistancetotheactionofthyroidhormoneHypothyroidismClinicalfeaturesCardiovascularsigns:BradycardiaLowvoltageECGPericardialeffusionCardiomegalyHyperlipidemiaConstipation,ascitesWeightgainColdintoleranceRough,dryskinPuffyfaceandhandsHoarse,huskyvoiceYellowishcolorofskinduetoreducedconversionofcarotenetovitaminARespiratoryfailureMenorrhagia,infertility,hyper-prolactinemiaRenalfunction:ImpairedabilitytoexcreteawaterloadAnemia:ImpairedHbsynthesisFedeficiencydueto:MenorrhagiaReducedintestinalabsorptionFolatedef.duetoimpairedintestinalabsorptionPerniciousanemiaNeuromuscularsystem:Musclecramps,myotoniaSlowreflexesCarpaltunnelsyndromeCNSsymptoms:Fatigue,lethargy,depressionInabilitytoconcentrateHypothyroidismDiagnosis:AiFT4andhTSHisdiagnosticofprimaryhypothyroidismSerumT3levelsarevariable(maybeinnormalrange)+vetestforthyroidautoantibodies(TgAb&TPOAb)PLUSanenlargedthyroidglandsuggestHashimoto’sthyroiditisWithpituitarymyxedemaFT4willbeibutserumTSHwillbeinappropriatelynormalorlowTRHtestmaybedonetodifferentiatepituitaryfromhypothalamicdisease.AbsenceofTSHresponsetoTRHindicatespituitarydeficiencyMRIofbrainisindicatedifpituitaryorhypothalamicdiseaseissuspected.Needtolookforotherpituitarydeficiencies.IfTSHish&FT4&FT3arenormalwecallthisconditionsubclinicalhypothyroidismHashimoto’sThyroiditisHashimoto’sthyroiditisisacommomcauseofhypothyroidismandgoitreespeciallyinchildrenandyoungadults.ItisanautoimmunediseasethatinvolvesheavyinfiltrationoflymphocytesthattotallydestroysnormalthyroidalarchitectureThreedifferentautoantibodiesarepresent:TgAb,TPOAb,andTSH-RAb(block)Itisfamilialandmaybeassociatedwithotherautoimmunediseasessuchasperniciousanemia,adrenocorticalinsufficiency,idiopathichypoparathyroidism,andvitiligo.Shmidt’ssyndromeconsistsofHashimoto’sthyroiditis,adrenalinsufficiency,hypoparathyroidism,DM,ovarianfailure,and(rarely)candidalinfections.Hashimoto’sThyroiditisSymptoms&Signs:UsuallypresentswithgoitreinapatientwhoiseuthyroidorhasmildhypothyroidismSexdistribution:fourfemalestoonemaleTheprocessispainlessOlderpatientsmaypresentwithseverehypothyroidismwithonlyasmall,firmatrophicthyroidglandTransientsymptomsofthyrotoxicosiscanoccurduringperiodsofhashitoxicosis(spontaneouslyresolvinghyperthyroidism)Lab:Normalorlowthyroidhormonelevels,andiflow,TSHiselevatedHighTgAband/orTPOAbtitresFNAbxrevealsalargeinfiltrationoflymphocytesPLUSHurthlecellsComplications:Permanenthypothyroidism(occursin10-15%ofyoungpts)Rarely,thyroidlymphomaManagementofHypothyroidismStartpatientonL-thyroxine0.05-0.1mgPOOD.L-thyroxinetreatsthehypothyroidismandleadstoregressionofgoitre.IfpatientiselderlyorhasIHDstart0.025mgPOOD.CheckTSHlevelafter4-6weekstoadjustthedoseofL-thyroxine.IncaseofsecondaryhypothyroidismmonitorFT4insteadofTSH.Hypothyroidismduringpregnancy:CheckTFTeverymonth.L-thyroxinedoserequirementtendstogoupasthepregnancyprogresses.Ifpatienthasconcommitanthyperprolactinemiaandhypercholesterolemia,treatifnotnormalizedafteradequatethyroidreplacement.MyxedemaComaMedicalemergency,endstageofuntreatedhypothyroidismCharacterizedbyprogressiveweakness,stupor,hypothermia,hypoventilation,hypoglycemia,hyponatremia,shock,anddeathThepatient(orafamilymember)mayrecallpreviousthyroiddisease,radioiodinetherapy,orthyroidectomyHxisofgradualonsetoflethargyprogressingtostupororcoma.AhxofamenorrheaorimpotencewithpituitarymyxedemaPErevealsiHRandmarkedhypothermia(aslowas24C)Theptisusuallyanobeseelderlywomanwithyellowishskin,ahoarsevoice,alargetongue,thinhair,puffyeyes,ileus,andslowreflexes.Ananteriorneckscarmaybepresent.ScantypubicoraxillaryhairwithpituitarymyxedemaLab:lowFT4,TSHhigh,normal,orlow,cholesterolhighorN,serumNalowECG:bradycardiaandlowvoltageMaybepptbyHF,pneumonia,excessivefluidadministration,narcoticsManagementofMyxedemaComaInitiatetherapyifpresumptiveclinicaldiagnosisafterTSH,FT3FT4drawn.Alsodrawserumcortisol,ACTH,glucose.Generalmeasures:PatientshouldbeinICUsettingSupportventilationasrespiratoryfailureisthemajorcauseofdeathinmyxedemacomamonitorsABG`ssupportbloodpressure;hypotensionmayrespondpoorlytopressoragentsuntilthyroidhormoneisreplacedhypothermiawillrespondtothyroxintherapy;ininterimusepassive

warmingonlyhyponatremiawillalsobecorrectedbythyroxinetherapyinmajorityofcaseshypoglycemiarequiresIVglucoseavoidfluidoverloadManagementofMyxedemaComaSpecificmeasure:L-thyroxine0.2-0.5mgIVbolus,followedby0.1mgIVODuntiloraltherapyistoleratedResultsinclinicalresponseinhoursAdrenalinsufficiencymaybeprecipitatedbyadministrationofthyroidhormonethereforehydrocortisone100mgIVq8hisusuallygivenuntiltheresultsoftheinitialplasmacortisolisknown.Identifyandtreattheunderlyingprecipitantcause

Graves’DiseaseMostcommonformofthyrotoxicosisMayoccuratanyagebutmostlyfrom20-405timesmorecommoninfemalesthaninmalesSyndromeconsistsofoneormoreofthefollowing:ThyrotoxicosisGoitreOpthalmopathy(exopthalmos)andDermopathy(pretibialmyxedema)Itisanautoimmunediseaseofunknowncause15%ofptswithGraves’haveacloserelativewiththesamedisorderGraves’DiseasePathogenesis:TlymphocytesbecomesensitizedtoAgwithinthethyroidglandandstimulateBlymphocytestosynthesizeAbtotheseAgOnesuchAbistheTSH-RAb(stim),whichstimulatesthyroidcellgrowthandfunctionGraves’maybepptbypregnancy,iodideexcess,viralorbacterialinfections,lithiumtherapy,glucocorticoidwithdrawalTheopthalmopathyanddermopathyassociatedwithGraves’mayinvolvelymphocytecytokinestimulationoffibroblastsintheselocationscausinganinflammatoryresponsethatleadstoedema,lymphocyticinfiltration,andglycosaminoglycansdepositionThetachycardia,tremor,sweating,lidlag,andstareinGraves’isduetohyperreactivitytocatecholaminesandnotduetoincreasedlevelsofcirculatingcatecholaminesGraves’DiseaseClinicalfeatures:IEyefeatures:Classes0-6,mnemonic“NOSPECS”Class0:NosignsorsymptomsClass1:Onlysigns(lidretraction,stare,lidlag),nosymptomsClass2:Softtissueinvolvement(periorbitaledema,congestionorrednessoftheconjunctiva,andchemosis)Class3:Proptosis(measuredwithHertelexopthalmometer)Class4:ExtraocularmuscleinvolvementClass5:CornealinvolvementClass6:Sightloss(opticnerveinvolvement)Graves’DiseaseClinicalfeatures:IIGoitre:DiffuseenlargementofthyroidBruitmaybepresentIIIThyroiddermopathy(pretibialmyxedema):ThickeningoftheskinespeciallyoverthelowertibiaThedermopathymayinvolvetheentirelegandmayextendontothefeetSkincannotbepickedupbetweenthefingersRare,occursin2-3%ofpatientsUsuallyassociatedwithopthalmopathyandveryhTSH-RAbGraves’DiseaseClinicalfeatures:IVHeatintoleranceVCardiovascular:Palpitation,AtrialfibrillationCHF,dyspnea,anginaVIGastrointestinal:Weightloss,happetiteDiarrheaVIIReproductive:amenorrhea,oligo-menorrhea,infertilityGynecomastiaVIIIBone:OsteoporosisThyroidacropachyIXNeuromuscular:Nervousness,tremorEmotionallabilityProximalmyopathyMyastheniagravisHyper-reflexia,clonusPeriodichypokalemicparalysisXSkin:PruritusOnycholysisVitiligo,hairthinningPalmarerythemaSpiderneviGraves’DiseaseDiagnosis:LowTSH,HighFT4and/orFT3Ifeyesignsarepresent,thediagnosisofGraves’diseasecanbemadewithoutfurthertestsIfeyesignsareabsentandthepatientishyperthyroidwithorwithoutagoitre,aradioiodineuptaketestshouldbedone.Radioiodineuptakeandscan:ScanshowsdiffuseuptakeUptakeisincreasedTSH-RAb(stim)isspecificforGraves’disease.Maybeausefuldiagnostictestinthe“apathetic”hyperthyroidpatientorintheptwhopresentswithunilateralexopthalmoswithoutobvioussignsorlaboratorymanifestationsofGraves’diseaseTreatmentofGrave’sDiseaseThereare3treatmentoptions:MedicaltherapySurgicaltherapyRadioactiveiodinetherapyTreatmentofGrave’sDiseaseA.Medicaltherapy:Antithyroiddrugtherapy:MostusefulinpatientswithsmallglandsandmilddiseaseTreatmentisusuallycontinuedfor12-18monthsRelapseoccursin50%ofcasesThereare2drugs:Neomercazole(methimazoleorcarbimazole):start30-40mg/Dfor1-2mthenreduceto5-20mg/D.Propylthiouracil(PTU):start100-150mgevery6hrsfor1-2mthenreduceto50-200onceortwiceadayMonitortherapywithfT4andTSHS.E.:5%rash,0.5%agranulocytosis(fever,sorethroat),rare:cholestaticjaundice,hepatocellulartoxicity,angioneuroticedema,acutearthralgiaManagementofGrave’sdiseaseA.Medicaltherapy:Propranolol10-40mgq6hrstocontroltachycardia,hypertensionandatrialfibrillationduringacutephaseofthyrotoxicosis.ItiswithdrawngraduallyasthyroxinelevelsreturntonormalOtherdrugs:Ipodatesodium(1gOD):inhibitsthyroidhormonesynthesisandreleaseandpreventsconversionofT4toT3Cholestyramine4gTIDlowersserumT4bybindingitinthegutManagementofGrave’sdiseaseB.Surgicaltherapy:SubtotalthyroidectomyisthetreatmentofchoiceforpatientswithverylargeglandsThepatientispreparedwithantithyroiddrugsuntileuthyroid(about6weeks).Inaddition2weeksbeforetheoperationpatientisgivenSSKI5dropsBIDtodiminishvascularityofthyroidglandComplications(1%):HypoparathyroidismRecurrentlaryngealnerveinjuryManagementofGrave’sDiseaseC.Radioactiveiodinetherapy:PreferredtreatmentinmostpatientsCanbeadministeredimmediatelyexceptin:ElderlypatientsPatientswithIHDorothermedicalproblemsSeverethyrotoxicosisLargeglands>100gInabovecasesitisdesirabletoachieveeuthyroidstatefirstHypothyroidismoccursinover80%ofcases.Femaleshouldnotgetpregnantfor6-12mafterRAI.ManagementofGrave’sDiseaseManagementofopthalmopathy:ManagementinvolvescooperationbetweentheendocrinologistandtheopthalmologistAcourseofprednisoneimmediatelyafterRAItherapy100mgdailyindivideddosesfor7-14daysthenonalternatedaysingraduallydiminishingdosagefor6-12weeks.KeepheadelevatedatnighttodiminishperiorbitaledemaIfsteroidtherapyisnoteffectiveexternalx-raytherapytotheretrobulbarareamaybehelpfulIfvisionisthreatenedorbitaldecompressioncanbeusedManagementofGrave’sDiseaseManagementduringpregnancy:RAIiscontraindicatedPTUispreferredoverneomercazoleFT4ismaintainedintheupperlimitofnormalPTUcanbetakenthroughoutpregnancyorifsurgeryiscontemplatedthensubtotalthyroidectomycanbeperformedsafelyinsecondtrimesterBreastfeedingisallowedwithPTUasitisnotconcentratedinthemilkToxicAdenoma

(Plummer’sDisease)ThisisafunctioningthyroidadenomaTypicalptisanolderperson(usually>40)whohasnotedrecentgrowthofalong-standingthyroidnoduleThyrotoxicsymptomsarepresentbutnoinfiltrativeopthalmopathy.PErevealsanoduleononesideLab:lowTSH,highT3,slightlyhighT4Thyroidscanreveals“hot”nodulewithsuppresseduptakeincontralaterallobeToxicadenomasarealmostalwaysfollicularadenomasandalmostnevermalignantTreatment:sameasforGrave’sdiseaseToxicMultinodularGoitreUsuallyoccursinolderptswithlong-standingMNGPErevealsaMNGthatmaybesmallorquitelargeandmayevenextendsubsternallyRAIscanrevealsmultiplefunctioningnodulesintheglandorpatchydistributionofRAIHyperthyroidisminptswithMNGcanoftenbepptbyiodideintake“jodbasedowphenomenon”.AmiodaronecanalsoppthyperthyroidisminptswithMNGTreatment:SameasforGrave’sdisease.Surgeryispreferred.SubacuteThyroiditisAcuteinflammatorydisorderofthethyroidglandmostlikelyduetoviralinfection.Usuallyresolvesoverweeksormonths.Symptoms&Signs:Fever,malaise,andsorenessintheneckInitially,thepatientmayhavesymptomsofhyperthyroidismwithpalpitations,agitation,andsweatPE:Noopthalmopathy,ThyroidglandisexquisitelytenderwithnosignsoflocalrednessorheatsuggestiveofabscessformationSignsofthyrotoxicosisliketachycardiaandtremormaybepresentLab:Initially,T4&T3areelevatedandTSHislow,butasthediseaseprogressesT4&T3willdropandTSHwillriseRAIuptakeinitiallyislowbutastheptrecoverstheuptakeincreasesESRmaybeashighas100.ThyroidAbareusuallynotdetectableinserumSubacuteThyroiditisManagement:InmostcasesonlysymptomaticRxisnecessarye.g.acetaminophen0.5gfourtimesdailyIfpain,fever,andmalaisearedisablingashortcourseofNSAIDoraglucocorticoidsuchasprednisone20mgthreetimesdailyfor7-10daysmaybenecessarytoreducetheinflammationL-thyroxineisindicatedduringthehypothyroidphaseoftheillness.10%ofthepatientswillrequireL-thyroxinelongtermOtherFormsofThyrotoxicosisThyrotoxicosisFactitia:DuetoingestionofexcessiveamountsofthyroxineRAIuptakeisnilandserumthyroglobulinislowStrumaOvarii:TeratomaoftheovarywiththyroidtissuethatbecomeshyperactiveNogoitreoreyesigns.RAIuptakeinneckisnilbutbodyscanrevealsuptakeofRAIinthepelvis.Hydatidiformmole:ChorionicgonadotropinisproducedwhichhasintrinsicTSH-likeactivity.TSH-secretingpituitaryadenoma:FT4&FT3iselevatedbutTSHisnormalorelevatedVisualfieldexaminationmayrevealtemporaldefects,andCTorMRIofthesellausuallyrevealsapituitarytumour.Thyroidstorm(Thyrotoxiccrisis)Usuallyoccursinaseverelyhyperthyroidpatientcausedbyaprecipitatingeventsuchas:InfectionSurgicalstressStoppingantithyroidmedicationinGraves’diseaseClinicalcluesfeverhyperthermiamarkedanxietyoragitationcomaAnorexiatachycardiatachyarrhythmiaspulmonaryedema/cardiacfailurehypotensionshockconfusionThyroidstorm(Thyrotoxiccrisis)InitiateprompttherapyafterfreeT4,freeT3,andTSHdrawnwithoutwaitingforlaboratoryconfirmation.

Therapy1.Generalmeasures:

Fluids,electrolytesandvasopressoragentsshouldbeusedasindicatedAcoolingblanketandacetaminophencanbeusedtotreatthepyrexiaPropranololforbeta–adrenergicblockadeandinadditioncausesdecreasedperipheralconversionofT4T3butwatchforCHF.

TheIVdoseis1mg/minuntiladequatebeta-blockadehasbeenachieved.Concurrently,propranololisgivenorallyorviaNGtubeatadoseof60to80mgq4hThyroidstorm(Thyrotoxiccrisis)Therapy2.SpecificMeasures:PTUistheanti-thyroiddrugofchoiceandisusedinhighdoses:1000mgofPTUshouldbegivenp.o.orbecrushedandgivenvianasogastrictube,followedbyPTU250mgp.o.q6h.IfPTUunavailablecangivemethimazole30mgp.o.every6hours.OnehouraftertheloadingdoseofPTUisgiven–giveiodidewhichacutelyinhibitsreleaseofthyroidhormone,i.e.Lugol’ssolution2-3dropsq8hORpotassiumiodide(SSKI)5dropsq8h.Dexamethasone2mgIVq6hforthefirst24-48hourslowersbodytemperatureandinhibitsperipheralconversionofT4-T3Withthesemeasuresthepatientshouldimprovedramaticallyinthefirst24hours.3.Identifyandtreatprecipitatingfactor.NontoxicGoitreEnlargementofthethyroidglandfromTSHstimulationwhichinturnresultsfrominadequatethyroidhormonesynthesisEtiology:IodinedeficiencyGoitrogeninthedietHashimoto’sthyroiditisSubacutethyroiditisInadequatehormonesynthesisduetoinheriteddefectinthyroidalenzymesnecessaryforT4andT3biosynthesisGeneralizedresistancetothyroidhormone(rare)Neoplasm,benignormalignantNontoxicGoitreSymptomsandSigns:Thyroidenlargement,diffuseormultinodularHugegoitresmayproduceapositivePembertonsign(facialflushinganddilationofcervicalveinsonliftingthearmsoverthehead)especiallywhentheyextendinferiorlyretrosternallyPressuresymptomsintheneckwithupwardordownwardmovementoftheheadDifficultyswallowing,rarelyvocalcordparalysisMostptsareeuthyroidbutsomearemildlyhypothyroid

RAIuptakeandscan:Uptakemaybenormal,low,orhighdependingontheiodidepoolScanrevealspatchyuptakewithfocalareasofincreasedanddecreaseduptakecorrespondingto“hot”and“cold”nodulesrespectivelyManagementofNontoxicGoitreL-thyroxinesuppressivetherapy:Dosesof0.1to0.2mgdailyisrequiredAimistosuppressTSHto0.1-0.4microU/L(N0.5-5)Suppressiontherapyworksin50%ofcasesifcontinuedfor1yearIfsuppressiondoesnotworkorifthereareobstructivesymptomsfromthestartthensurgeryisnecessaryBenignThyroidNodulesThyroidnodulesarecommonespeciallyamongolderwomenEtiology:FocalthyroiditisDominantportionofmultinodulargoitreThyroid,parathyroid,orthyroglossalcystsAgenesisofathyroidlobePostsurgicalremnanthyperplasiaorscarringPostradioiodineremnanthyperplasiaBenignadenomas:FollicularColloidormacrofollicularHurthlecellEmbryonalRare:Teratoma,lipoma,hemangiomaThyroidCancerApproximatefrequencyofmalignantthyroidtumoursPapillarycarcinoma(includingmixedpapillaryandfollicular75%Follicularcarcinoma16%MedullaryCarcinoma5%Undifferentiatedcarcinomas3%Miscellaneous(e.g.lymphoma,fibrosarcoma,squamouscellca,teratoma,&metastaticca)1%PapillaryCarcinomaUsuallypresentsasanodulethatisfirm,solitary,“cold”onisotopescan,andusuallysolidonthyroidUSInMNG,thecancerisusuallya“dominantnodule”thatislarger,firmeranddifferentfromtherestofthegland10%ofpapillarycapresentwithenlargedcervicalnodesGrowsveryslowlyandremainsconfinedtothethyroidglandandlocallymphnodesformanyyears.InlaterstagestheycanspreadtothelungDeathusuallyfromlocaldiseaseorlungmetastasesMayconverttoundifferentiatedcarcinomaManyofthesetumourssecretethyroglobulinwhichcanbeusedasamarkerforrecurrenceormetastasisofthecancerFollicularCarcinomaDiffersfromfollicularadenomabythepresenceofcapsularorvascularinvasionMoreaggressivethanpapillarycaandcanspreadeitherbylocalinvasionoflymphnodesorbybloodvesselinvasionwithdistantmetastasestoboneorlungDeathisduetolocalextensionortodistantbloodstr