内科学英文ppt课件 ：Hyperthyroidism-甲状腺功能亢进症.ppt

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1、Hyperthyroidism甲状腺功能亢进症Department of Endocrinology and Metabolism diseases,Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong UniversityParafollicular CellsColloidFollicular CellsGeneral Introduction of ThyroidFollicleFollicles:the Functional Units of the Thyroid GlandRegulation of thyroid hormon

2、e secretion Regulation of thyroid hormone secretion Regulation of thyroid hormone secretion Regulation of thyroid hormone secretion TRHTSH.(Cold,Emotions)TSHTH.TRH/TSH Stimulating test THTSH (Negative feedback)Stimulate InhibitHyperthyroidism（甲亢）is defined as anoveractivethyroidgland,whichproducesan

3、dsecretesexcessiveamountsofthyroidhormones-triiodothyronine(T3)andthyroxine(T4).Hyperthyroidism（甲亢）is defined as anoveractivethyroidgland,whichproducesandsecretesexcessiveamountsofthyroidhormones-triiodothyronine(T3)andthyroxine(T4).Thyrotoxicosis(甲状腺毒症）Hyperthyroidism（甲亢）is defined as anoveractivet

4、hyroidgland,whichproducesandsecretesexcessiveamountsofthyroidhormones-triiodothyronine(T3)andthyroxine(T4).Thyrotoxicosis(甲状腺毒症）isclinicalsyndromewhentissues are exposed to excessive concentrations ofthyroidhormones.Hyperthyroidismsustainedoverproductionandreleaseofhormonebythethyroiditself1.Graves

5、disease2.multiple nodular thyrotoxicosis(多结节性毒性甲状腺肿）多结节性毒性甲状腺肿）3.plummer disease/toxic thyroid adenoma（自主功能性甲状腺腺瘤）（自主功能性甲状腺腺瘤）4.iodine-induced hyperthyroidism(碘甲亢碘甲亢)5.neonatal hyperthyroidism(新生儿甲亢新生儿甲亢)6.pituitary TSHoma(垂体垂体TSHTSH腺瘤腺瘤)7.others(甲状腺癌等甲状腺癌等)Etiology of thyrotoxicosis Non-thyroidthyr

6、otoxicosisnotoverproductionofthyroidhormonesbythyroid1.subacute thyroiditis(亚急性甲状腺炎亚急性甲状腺炎)2.asymptomatic thyroiditis(无症状型甲状腺炎无症状型甲状腺炎)3.chronic lymphocytic thyroiditis(桥本甲状腺炎桥本甲状腺炎)4.postpartum thyroiditis(产后甲状腺炎产后甲状腺炎 PPT)5.HCG related hyperthyroidism(HCG 相关性甲亢相关性甲亢)6.Iatrogenic hyperthyroidism(医源

7、性甲状腺激素替代医源性甲状腺激素替代)7.Ectopic goiter with hyperthyroidism(异位甲状腺激素产生异位甲状腺激素产生)Etiology of thyrotoxicosis GRAVES DISEASE(GD)ItiswrongtosayGravesdisease(Graves病病）ashyperthyroidism(甲亢甲亢）inbrief.甲亢甲亢GDHyperthyroidismThyrotoxicosisGraves DiseaseGraves disease(GD)pathogenesishistopathologyclinicalpresentati

8、onlaboratoryandspecialexamsdiagnosisanddifferentialdiagnosistreatmentOutline of GDOrgan-specificautoimmunediseaseDiffusetoxicgoiterSymptoms：thyroidenlargement，thyrotoxicosis，exophthalmos(突眼），pretibialmyxedema（胫前黏液性水肿）Morecommonlyinwomen，Female：Male=46：1SubclinicalhyperthyroidismisusuallyreferredtoaG

9、DstatewithnormalT3T4,decreasedTSH,andnoclinicalsymptomsofhyperthyroidismPathogenesisAbnormalitiesofimmunesystemBcellsproduceTSH-R-Ab(TRAb)TRAbTSAb:stimulatingIgG-hyperfunction-直接病因TSBAb:inhibitoryIgG-hypofunctionandantagonistofTSAbTGI（thyroidgrowthimmunoglobulins）:growth-stimulatingIgGTSH-R+TRAbmimi

10、ctheactionofTSH-hyperfunctionandgoiterHereditary(geneticfactors)HLA-B8、DR3、DQA1*0501、HLA-Bw46CTLA-4GD-1,-2,and-3EnvironmentandInfectioninfectivefactors(Yersiniaenterocolitica）stress(physicaloremotional)Estrogen,pregnancy,childbirthPathogenesisHistopathologyThyroidgoiter:symmetrical(对称），diffuse(弥漫性）f

11、ollicles:hyperplasticcolumnwithscantcolloid（滤泡细胞增生肥大，呈柱状、胶质少）,papillaryprojections（乳头样突起）vascularityincreased(血管增生）lymphocytesandplasmacellsinfiltration(淋巴细胞和浆细胞浸润）Thevolumeoforbitalcontentsisenlargedbecauseofincreasesinretrobulbarconnectivetissueandadiposetissue 眼球后脂肪和结缔组织水肿、浸润、体积增大Theextraocularmu

12、sclesareswollen,andsomefibersexhibitlossofstriation,fragmentation,andlymphocyticinfiltration 眼外肌肌炎，淋巴细胞浸润、肌纤维水肿、断裂、坏死，眼外肌体积增大 眼肌增大及纤维化使眼肌自身的活动障碍，引起复视。眼肌增大及纤维化使眼肌自身的活动障碍，引起复视。眼睑挛缩和眼球凸出共存，引起暴露性角膜炎。眼睑挛缩和眼球凸出共存，引起暴露性角膜炎。球后组织增生，压力增。高，压迫视神经引起视神经病变。球后组织增生，压力增。高，压迫视神经引起视神经病变。眼眶炎症及眶引流障碍，引起球结膜水肿和眶周水肿眼眶炎症及眶引流障

13、碍，引起球结膜水肿和眶周水肿HistopathologyOphthalmopathySkinswellingGlycosaminoglycanaccumulationintheskinandsubcutaneoustissue,collagenfiber,connectivetissuedamage（粘蛋白沉积，胶原及结缔组织损伤）Mastcells,macrophagesandfibroblastscellsinfiltration(肥大细胞，吞噬细胞和成纤维细胞浸润）HistopathologyPretibialmyxedema（胫前黏液性水肿）Clinical PresentationS

14、ymptomsandsignsassociatedwithelevatedlevelsofthyroidhormonesGoiterOphthalmopathySpecialmanifestationsHighmetabolismNervoussystemCardiovascularsystemGastrointestinalsystemHematopoieticsystemGonadalsystemMusclesThyrotoxicosis:High metabolism:DontEvadeFeelingHotAndSweatyPatientsWeightloss(despitenormal

15、energyintake)FatiguesandweaknessHeatintoleranceandlowfeverIncreasedsweatingGlucoseintoleranceHigh metabolism:Nervous systemNervous systemNervousnessEmotionallabilityAnxietyandirritabilityDifficultysleepingHyperactivityandunabletoconcentrateTremorandmuscleweaknessTendonreflexeshyperactivityApathy,dep

16、ressionandwithdrawninolderpatientsCardiovascular systemCardiovascular systemPalpitation（心悸）Tachycardia(心动过速90bpm)Atrialfibrillation（房颤）andotheratrialarrhythmias（室颤）PulsepressureisincreasingAccentuatedheartsounds,systolicejectionorothermurmurs（收缩期杂音）Gastrointestinal systemGastrointestinal systemIncre

17、asedappetiteHyperdefecationSteatorrhea(脂肪泻）Jaundice（黄疸）ImpairedoftheliverfunctionHematopoietic systemHematopoietic systemMildgranulocytopenia（粒细胞减少）Ironorotherhematopoieticnutrientdeficiencyanemia（贫血）Gonadal system（性腺）Gonadal system（性腺）InfrequentmenstruationorsuppressedmenstruationErectiledysfunctio

18、nandoccasionallylossoflibido（性欲）Gynecomastia（男子乳腺发育）MuscleMuscleMuscleweaknessThyrotoxicmyopathy（甲状腺毒性肌病）TPP-thyrotoxicperiodicparalysis（甲亢性周期性瘫痪）Multiple system involvementNervous system肢端肢端Gonadal systemCardiovascular systemGastrointestinal systemMusclesSkin appendagesHematopoietic systemEndocrine

19、 systemCardiovascular systemGonadal systemMusclesTPP-thyrotoxic periodic aralysisClinical Presentationthyrotoxicosis(hypermetabolicstate)nervousness(精神紧张 99%）,irritability（烦躁90%）,palpitation（心慌88%）,tachycardia（心动 过 速 82%）,insomnia（失 眠 60%）,fatigue（70%）,heatintolerance（70%）,excessivesweating（40%）,wei

20、ghtloss（75%）,withvoraciousappetite（食欲亢进65%）Clinical Presentationthyroidgoiter（、）、nontenderthrillwithaudiblebruit(震颤、血管杂音）ExophthalmosNon-infiltratingexophthalmosClinical Presentationmild proptosis,18mm),visualacuritydecrease（视力下降）,visualfielddefect（视野缺损）,cornealulceration（角膜溃疡）,restrictionofeyemovem

21、entClinical PresentationExophthalmosProbability of the development of orbitopathy in patients with Graves disease PretibialmyxedemaClinical PresentationIntheanteriortibial,dorsalfootIntheanteriortibial,dorsalfoot多见于胫前、足背多见于胫前、足背Theskinisthickandhard,likeorangepeelTheskinisthickandhard,likeorangepeel

22、皮肤厚而硬，酷似橘皮皮肤厚而硬，酷似橘皮thyroid stormhyperthyroidheartdiseaseapathetichyperthyroidismT3T4typehyperthyroidismsubclinicalhyperthyroidismpregnancyhyperthyroidismSpecial clinical manifestationscomplicationsThyroid storm(thyrotoxic crisis)precipitatingfactorsacuteillness:infection,trauma(创伤),DKAsurgery(espec

23、aillyonthethyroid)radiationthyroiditissymptomsandsignsexaggeratedabruptlyfever(39),sweating,vomiting,diarrheaandjaundice（黄疸）increasedheartrate,arrhythmias（心律失常），congestiveheartfailure（充血性心衰），hypotension,shockrestlessness(烦躁），delirium(谵妄）,seizures（抽搐）,apathy（淡漠）,stupor（木僵）,coma（昏迷）Hyperthyroid crisis

24、 is a life threatening formHyperthyroid heart diseasefeaturesasheartenlargementarrhythmiasheartfailureothercausesexcludeddisappearedaftertreatmentApathetic hyperthyroidismMorecommoninolderpatientsInsidiousonset,highmetabolicsyndromegroup,eyesymptoms,goiterisnotobviousMainpresentations:weightloss,hea

25、rtpalpitations,fatigue,diarrhea,anorexia(厌食）,apathy（淡漠）,atrialfibrillationeasilybemisdiagnosedDiagnosticclues:suddenweightloss,newonsetatrialfibrillationT3T4 type hyperthyroidismT3hyperthyroidismOnly5%ofhyperthyroidismRatiogeneratingT3andT4disorders,T3T4commonlyiniodinedeficiencyregionandintheelderl

26、ypopulationcauses:GD,toxicnodularthyroidtumorsandhigh-functioningadenomasRemissionrateishigherthanthetypicalhyperthyroidismT4hyperthyroidismcausesiodine-inducedhyperthyroidismhyperthyroidismwithsystemicdisease(peripheraldeiodinaseactivityreducedorlack)Subclinical hyperthyroidismcauses:GD,nodulargoit

27、er,thyroidadenomaandotherhigh-functioningdiseaseprocess:earlystageorconvalescence(恢复期）adverseoutcomesApproximately4-10%peryearforthedevelopmentofsub-clinicalhyperthyroidismtohyperthyroidismImpactonthecardiovascularsystemOsteoporosis,fractureriskPregnancy hyperthyroidismHCGrelatedtohyperthyroidismGes

28、tationaltransienthyperthyroidism(GTT)incidence:2-3%increasedHCGstimulatesTSHreceptornoproptosis,autoantibody(-),peakedat3monthsofpregnancyseverecases:canbeshort-termATDtherapyhyperthyroidismduringpregnancyWithdiffusegoiter,exophthalmos,thyroidbruitorthrill,TRABpositivediagnosis:FT3,FT4andTSH,notTT3/

29、TT4adverseconsequencesMother:miscarriage,prematurebirth,preeclampsia（先兆子痫),placentalabruption(胎盘早剥）Fetus:preterm(早产）,intrauterinegrowthretardation（宫内生长迟缓）Fetalorneonatal（新生儿）hyperthyroidismLaboratory and Special ExamsSerumTHandTSHTT3andTT4,FT3andFT4-increasedFT3andFT4arethedirectindexes(0.3%and0.02%

30、)TT3andTT4areinfluencedbyconcentrationofTBG(99.7%and99.98%)rT3-increasedTSH-decreasedTSHreceptorantibodies-TRAb（+）131Iuptake-increased，peakappearedbeforeNormalreferencerange:3h:5-25%,24h:20-45%Imagingexaminationultrasonographyemissioncomputerizedtomography(ECT)Diagnosis and Differential Diagnosiscon

31、firmedhyperthyroidismsymptomweightloss,slightfever,diarrhea,tachycardia（心动过速）,atrialfibrillation（房颤）,fatigue,withdifficultincontrolofDM,heartfailure,liverdiseasesignsdiffusegoiter,exophthalmoshormoneabnormalFT3,FT4,TSHpathogenicdiagnosisTRAb,TgAb(甲状腺球蛋白抗体),TPOAb(甲状腺过氧化物酶抗体)131IuptakeultrasonographyH

32、CGDifferent DiagnosisDifferent DiagnosisTRAbGraves甲亢T3,T4synthesisThyroiditisT3,T4release131I uptakeTreatmentGeneraltreatmentATD-reducing thyroid hormone synthesis Radioiodinetreatmentreducing the amount of thyroid tissue OperationGeneral managmentabsolutelyavoidiodineseafood,salt,tinctureofiodine(碘

33、酒),drugssuchasCentrum(善存),amiodarone(胺碘酮)restenoughenergyandnutrientssupplement(proteinandvB)sedatives(镇静剂)forrestlessnessandinsomnia(失眠)betablockers(propranolol)fortachycardiaintheearlystagesbeforeantithyroiddrugstakeeffectVaidyaetalClinEndocrinol2008ATDtherapyisthefirstchoiceinEuropeandAsiaAntithy

34、roid drugs(ATD)agentsmethylthiouracil(MTU)orpropylthiouracil(PTU)300-600mg/dmethimazole(MM)orcarbimazole(CMZ)30-60mg/dmechanisminhibitthefunctionofTPO,reducingoxidationandorganificationofiodidereducethyroidantibodylevels(mechanismsunclear)InhibitionofthyroidfollicularepithelialcellfunctionandgrowthP

35、TUinhibitsdeiodinationofT4toT3severethyrotoxisisIndicationsmildtomoderatepatientsthyroidmildtomoderateswellingyoungpeople(20yrs)pregnantwomen,theelderlypatientsnotsuitableforsurgeryorradioactiveiodinetreatmentpreparationbeforesurgeryorradioactiveiodinetherapyrecurrenceaftersurgeryAntithyroid drugs(A

36、TD)dosageandcourse1ststage(6wks)：fulldosagetocontrolsymptoms2ndstage(4-8wks):dosagedecreasegradually3rdstage(1yrormore）：minimaldosagetomaintaintreatedeffectsblock-replaceregimensTHaddedtopreventionofhypothyroidismregulationofimmunedrugwithdrawalgoitersubsidesTSHreturntonormalTSAb/TRAbnegtivemaximumr

37、emissionratesareachievedby18-24monthsAntithyroid drugs(ATD)sideeffectsLowdoseofMMIrarelyhavesideeffectswhilePTUcancauseitinanydosecommon:rash(皮疹）,urticaria（荨麻疹）,fever,andarthralgia（关节痛）（1-5%ofpatients)hepatitis,anSLE-likesyndromeLeukocytopenia(粒细胞减少）andagranulocytosis(粒细胞缺乏症）（1%,within2months)can be

38、 caused by hyperthyroidism itself,so take a blood routine before treatmentAnti-NeutrophilCytoplasmicAntibodies（ANCA）positivevasculities,Aplasticanemia(再生障碍性贫血）monitorbloodcountsandlivefunction:wkormomostofthemweretransientthatneedntstopthetreatmentAntithyroid drugs(ATD)Agranulocytosis(粒细胞缺乏症）Theinci

39、dencerateis0.2%-0.5%,themostseveresideeffect,bothPTUandMMIcancauseitnormallyhappenswithin3monthsoftreatmentSorethroat,fever,infectionetc.WBC3x109/L,neutrophilcells22)4Eextraocularmuscleinvolvement眼外肌受累5Ccornealinvolvement角膜受累6Ssightloss视力丧失Classification of Graves orbitopathy:NOSPECS3-6 CAN BE DIAGN

40、OSED GOAssessment of the activity of GOClinicalActivityScore（CAS）Spontaneousretrobulbar(球后)painPainoneyemovementEyeliderythema(眼睑发红)Conjunctivalinjection(结膜充血)Chemosis(球结膜水肿)Swellingofthecaruncle(眼阜肿胀)Eyelidedema(水肿)orfullnessEachmanifestationassigned1point，CAS3分为GO活动ThehigherCAS,thehigheractivityAs

41、sessment of the severity of GO (UGOGO)分分 级级上睑挛缩上睑挛缩 软组织受累软组织受累突突 眼眼复复 视视 角膜暴露角膜暴露视视N压迫压迫轻度轻度2mm轻度轻度3mm无或者一无或者一过性过性无无无无中重度中重度 2mm中重度中重度 3mm间断或持间断或持久久轻度轻度无无威胁视力威胁视力重度重度有有中国人群的正常突眼度：18.6mmATA/AACE：甲亢处理指南：甲亢处理指南 2010眼球运动障碍眼球运动障碍角膜外露角膜外露软组织炎症软组织炎症视神经损伤视神经损伤突眼突眼眼睑挛缩眼睑挛缩Courtesy of Dr.Petros PerrosManageme

42、nt of nonsevere GOManagementSignsorsymptomsSunglassesArtificialtearsandointmentsb-BlockingeyedropsNocturnaltapingoftheeyesPrisms（棱镜）Correctionofhyper-orhypothyroidismEliminationofriskfactors(smoking)Photophobia(畏光）Foreignbodysensation（异物感）Eyelidretraction;increasedintraocularpressureLagophthalmos（眼睑

43、闭合不全）Milddiplopia（轻度复视）LUIGI BARTALENA,ER 2000Management of severe GOEstablishedmethods:Glucocorticoids(Oral,Intravenous,Local)Supervoltageorbitalradiotherapy（超高压眼眶放射治疗）Rehabilitative（康复）surgery(Orbitaldecompression眶减压,Extraocularmusclesurgery,Eyelidsurgery)Noveltreatmentsunderinvestigation:Somatost

44、atinAnalogues（生长抑素类似物）Octreotide（奥曲肽）Lanreotide（兰瑞肽）Intravenousimmunoglobulins（免疫球蛋白）Nonestablishedmethods:Cyclosporinea（环孢素）Plasmapheresis（血浆置换）LUIGI BARTALENA,ER 2000 GO患者患者改善甲状腺功能改善甲状腺功能力劝戒烟力劝戒烟专科医院就诊专科医院就诊局部检查局部检查鼓励患者鼓励患者 轻度轻度中至重度中至重度威胁视力威胁视力局部检查局部检查等待等待-观察观察康复手术康复手术(必要时必要时)稳定无活动稳定无活动有活动有活动无活动无活

45、动糖皮质激糖皮质激素治疗素治疗(+/-眶放眶放疗疗)立即减压手术立即减压手术疗效欠佳疗效欠佳(1-2 周周)仍有活动仍有活动病情进展病情进展稳定无活动稳定无活动稳稳定无活动定无活动康复手术康复手术康复手术康复手术糖皮质激素治疗糖皮质激素治疗糖皮质激糖皮质激素治疗素治疗(+/-眶放眶放疗疗)Bartalena&EUGOGO,Thyroid&EJE 2008Treatment of subclinical hyperthyroidism If a sustained TSH suppression(If a sustained TSH suppression(0.1 mU/L0.1 mU/L)is

46、 established,then)is established,then managment should be based on an individual program.For managment should be based on an individual program.For example,patients with example,patients with 65yrs65yrs,symptomssymptoms,atrial fibrillationatrial fibrillation,unexplained weight lossunexplained weight

47、 loss,multinodular goitermultinodular goiter,women with women with osteoporosis.osteoporosis.p In patients over 60 years,the incidence of atrial fibrillation was 2.8 times of the same age groupp In postmenopausal women,bone turnover rate increased,bone mineral density decreasedp associated with Alzh

48、eimers diseasep potential risk of clinical hyperthyroidism，0.5-1.0%/year因素TSH(mU/L)0.010.010.05Age65是考虑治疗Age65，伴并发症心脏病是考虑治疗甲亢症状是考虑治疗骨质疏松是否绝经是否Age65,无症状考虑治疗否GravesdiseaseinpregnancyAntithyroiddrugsarethetreatmentchoicePTUispreferredthelowestpossibledoseofdrugshouldbeusedtomaintainthemothersthyroidfun

49、ctionattheupperlimitofnormal.pregnancyhasanameliorativeeffectbreastfeedingissafewithlowdosesofdrugsSurgeryifnecessary,itisbestdoneduringthesecondtrimester(4-6th)absolutecontraindications:radioiodinetreatmentNeonatal hyperthyroidismmotherTSAbthroughtheplacentamildcases:self-limiting,notreatmentsevere

50、cases:PTU10-25mg,q8hIodine-induced hyperthyroidismAvoidexcessiveintakeofiodineApplythe-blockersrelievesymptomsplusMMIseverecasesthreemonthswithoutremissionThyroidnodulescanbesurgicallyremovedRadioactiveiodinetreatmentisnotconsideredbeforeiodineisdrainedamiodaronetherapycausesthyroiddysfunctionin14-1