内分泌总论、甲亢(英文)廖二元课件

CLINICALENDOCRINOLOGY&METABOLISM—INTRODUCTIONANDGENERALCONCEPTS(总论)InstituteofMetabolism&EndocrinologyEryuanLiao()A.Therapidityandextensivenessofadvancesinendocrinologyhavemadeitincreasinglydifficultforthestudentsandphysicianstotakefulladvantageofinformationavailablefortheunderstanding,diagnosis,andtreatmentofclinicaldisorders,notonlyofdiseasesinendocrinology,butalsoofthatinall

clinical

specialties.B.Whateasytohandleisthatthegeneral

knowledgeandthe

principles

ofendocrinology

and

metabolism.C.Forinterest,beinterestedintheinterestingmedicalbranch.D.MainsubjectsMechanismsofhormoneactionNutrientmetabolismSystemicexaminationLaboratoryandspecialexaminationsTherapeuticprinciplesRegulationSystemsofExtra-CellularCommunicationnervoussystemendocrinesystemimmunesystemEndocrineGlandandHormone-SecretingCells（激素分泌细胞）A.Endocrineglanda.hypothalamus&posteriorpituitaryb.pinealgland(松果体)c.anteriorandintermedialpituitaryd.thyroide.parathyroidf.endocrinepancreas(内分泌胰腺)g.adrenalcortexandmedullah.sexualgland(testisorovary)i.others:thymus(胸腺)，placenta

Structureofhormone-secretingcells

peptide/proteinhormone-secretingcells:hormone-containinggranules

(激素颗粒)

steroidhormone-secretingcells:

lipiddroplet(脂质小滴)C.Typesofhormonesecretionendocrine(内分泌)paracrine(旁分泌)autocrine(自分泌)intracrine(胞内分泌)neurocrine(神经分泌)juxtacrine(并邻分泌)solinocrine(腔分泌)amphicrine(双重分泌)half-life:peptidesandprotein:minutessteroids:variable,hrsdegradationinliver,kedney,othertissues,orinhormone-secretingcells.E.Hormonedegradationandhalf-lifeA:Biologicalrhythms（生物节律）milliseconds:nerveimpulse,membraneelectrolytes.minutes:neurotransmittershours:LH,TRH,testosterone,cortisol,GH,prolactin,TSH,etcdays:FSHpeaksweeks:menorrheamonths:T4,1,25-(OH)2D3,pregnancySecretionRhythmsB.Circadianrhythms(昼夜节律)biological“clock”inhypothalamus(melatonin),butlostinCushingdiseaseandpsychosisC.24-hrchangesofserumandurinehormone(metabolicproducts)D.Heterogeneityofserumhormoneshormone,pro-hormone(激素原),prepro-hormone(前激素原)monomer,dimer,trimertetramer,etc.fragementofpeptides.A.Endocrineregulationactivehormonemoleculehormone-bindingproteinhormonereceptoronmembraneincytoplasmainnucleolus(nucleoplasm)post-receptortransduction(cascadereaction)tropic-hormone(促激素)feedbackcycletargetcellreactionHormoneSynthasesandItsRegulationA.HormoneregulationA:ultra-shortfeedback(超短反馈)B:shortfeedback(短反馈)C:positivefeedback(正反馈)D:longnegativefeedback(负反馈):stimulating;:inhibitoryAnerveimpulses/cytokinesCNShypothalamuspituitaryglandtargetglandDBEndocrineRegulationAxesB.Regulationaxes(调节轴)a.hypothalamus-pituitary-thyroid(adrenalcortex,sexualgland)b.GIH/GHRH-GH/GHBP-IGFs/IGFBPS-IGFBP/IGFBPasec.renin-AT-ALDinvolvedinrenin,AT,ALD,ANP,AVP,AM(adrenomedullin,肾上腺髓质素)A.Actedastranscription-regulatoryfactorssteroidhormonebindinwithreceptor(cytoplasmornucleoplasm)H-Rcomplex+DNAbindingdomaingeneexpressionproteinMechanismsofHormoneActionB.Actedatcellsurfacea.peptidehormone+membraneRpostreceptorcascadereactionb.typesofmembraneRG-proteincoupledreceptor(transmenbrane7times)involvedinPTH,AT,glucagon,LH,FSH,TSH,AVP,CT,HCG,etc.receptorkinases(transmembrane1time),withtyrosinekinase(activity),involvedininsulin,IGF,EGF,etc.receptor-linkedkinases,involvedinGH,PRL,leptinreceptorsofligand-gatedionchannels(transmembrane4or6times),involvedin5-HT,GABA,etc.A.Symptomandsignsa.bodyheight(geneticfactors,GH,TH,sexhormones,IGF-1,nutrition,systemicdiseases)b.obesityandweighloss(geneticconstitution,nutrition,systemicdisease,GH,TH,insulin,leptin,cortisol,sexhormones)c.polydipsiaandpolyuria(DM,ALD,hyperparathyroidism,DI)SystemicExaminationd.hypertensionwithhypokalemia(primaryhyperaldosteronism,reninoma,Cushingsyndrome)e.hyperpigmentation(ACTH,MSH,estrogen,progesterone,androgen)f.hairlossorhypertrichosis(hairy,多毛症)genetics,race,androgen.hypertrichosis:PCOS,congenitaladrenalhyperplasia,Cushingdisease,ovariantumors,hypothyroidism,drugs.hairloss:cortisol,androgen,g.gynecomastia(男性乳腺发育):Klinefeltersyndrome,testiculartumors,drugs.)h.exophthalmos(突眼)：Gravesdisease,chroniclymphocyticthyroiditis,eyediseases.)i.bonepainandfractures(osteoporosis,hyperparathyroidisim,boneorhematologicdiseases)C.Dynemictests(动态试验)stimulationtest(兴奋试验)：hypofunction(hypocortisolism)inhibitorystates(TSHinGD)suppressiontest(抑制试验)：hyperfunction(DXMforCushingdisease)therapeutictest(治疗试验):(spironolactonetreatmentinsuspectedhyperaldosteronism)provocationtest(glucagontestfordiagnosisofpheochromocytoma)X-rayfilm(bonediseases,kedneystones)CT&MRI(morphologicchanges)radionucleartomography(thyroid,pancreas,adrenalcortexandmedulla,parathyroid,etc)typeBUS(thyroid,adrenalcortex,ovary,testis)A.Pathogenictherapy:supplementofnutrients,genetreatment.B.Hypofunction:1.hormonereplacementtherapy(Addisondisease,hypothyroidism;hypogonadism)2.drugstostimulatehormonesecretion(sulfonylureafortype2DM)3.transplantation(organ,tissue,cells)TherapeuticPrinciplesC.Hyperfunction1.drugstosuppresshormonesecretion(iodideforGD,spironolactoneforhyperaldosteronism.SSforinsulinoma)2.radioactivetherapy(131IforGD,γ-knifeforpituitarytumors)HYPERTHYROIDISM(THYROTOXICOSIS,甲亢)Hyperthyroidismisonlyadiagnosisofexcessivethyroidhormonestatus,notaconcretediseaseorasyndrome.Itiswrongtosay“Gravesdisease(Graves病)”as“hyperthyroidism(甲亢)”inbrief.ThyroidaloriginGravesdiseasemultiplenodularthyrotoxicosis(多结节性毒性甲状腺肿) Plummerdisease(toxicthyroidadenoma) automatichyperfunctionalthyroidnodules(自主功能性甲状腺结节) multipleautoimuneendocrinesyndromewith hyperthyroidism(多发性自身免疫性内分泌腺病伴甲亢) thyroidcarcinomas neonatalhyperthyroidism genetictoxicthyroidhyperplasia/goiter iodine-inducedhyperthyroidism(碘甲亢)PathogenesisofHyperthyroidismPituitaryoriginpituitaryTSHomathyroidhormoneinsensitivitysyndrome(pituitarytype,垂体型TH不敏感综合征)paracarcinomasyndromeHCG-relatedhyperthyroidismcarcinomas(lung,GI,pancreas)withhyperthyroidismOvariangoiterwithhyperthyroidismIatrogenichyperthyroidism(医源性甲亢)TransienthyperthyroidismSubacutedeQuervianthyroiditis(肉芽肿性甲状腺炎)hymphocyticthyroiditis(postpartum,IFN,IL,Li)trumaticthyroiditisradioactivethyroiditisChronicchroniclymphocyticthyroiditisPathogenesisHistopathologyClinicalpresentationLaboratoryandspecialexamsDiagnosisanddifferentialdiagnosisTreatmentGRAVESDISEASE(GD)GDisalsocalled:diffusetoxicgoiter BasedowdiseaseSubclinicalhyperthyroidismisusuallyreferredtoaGDstatewith(ab)normalT3,T4,decreasedTSH,andnoclinicalsymptomsofhyperthyroidismGravesDisease(GD)A.Abnormalitiesofimmunesystema.TSH-R-Ab+TSH-RmimictheactionofTSHhyperfunctionandgoiter.b.functioningofIgThhypersensitivity+IL-1,IL-2BcellsproduceTSH-R-Ab(TRAb)Pathogenesis stimulatingIgGhyperfunction(TSAb)c.TRAb inhibitoryIgGhypofunctionandantagonist ofTSHRand TSAb(TF1Ab,TGBAb) growth-stimulatingIgG(TGI)B.Otherfactorsgeneticfactorsinfectivefactorsstress(physicaloremotional)C.Thyroid-associatedophthalmopathy(TAO)unknownGAG(葡萄聚糖)accumulation,Tcellinfiltration,edema,fibrosisandsightloss.A.Thyroidgoiter:symmetrical,diffuse,softenlargedaftertreatment:lobularfollicles:hyperplasticcolumnwithscantcolloid,papillaryprojections,vascularityincreasedlymphocytesandplasmacellsinfiltration

HistopathologyB.Eyesorbitalcontentsincreased,containingmucoprotein,GAG(glycosaminoglycan,葡糖聚糖),lymphocytes.C.Skin(dermopathy)hyaluronicacid(透明质酸),chondroitinsulfates(硫酸软骨素)increased,collagenfibersseparatednodularandplaqueformationlymphaticdrainagedecreasedA.Generalconsiderationsmale:female≈1:4~6,commonin30~40yrs.B.Hypermetabolicstatesnervousness(99%).irritability(90%),palpatation(88%),tachycardia(82%),insomnia(60%),fatigue(70%),heatintolerance(70%),excessivesweating(40%),weightloss(75%),withvoraciousappetite(65%),menstrualpatternchanged(50%)ClinicalPresentationC.Thyroiddiffusegoiter:absentintheelderly,consistency:soft,firm,rubbery,symmetricalenlarged,surface:smooth,lobular,thrillwithaudible

bruit

eyelidspasmorretractionD.

Eyesa.non-infiltrativeorbitopathy:fissurewidened,scleraexposed,lidretraction,lidtremor,lidlay,globelay.b.infiltrative

orbitopathy: excessivetearing exophthalmos(asymmetrical) eyelidsunclosed blurredvision doublevision visualacuitydecreased corneasulcerated,infected sightlossc.ClassificationofGravesorbitopathy:NOSPECS

(from:AmericanThyroidAssociation)Class Definition0 Nophysicalsignsorsymptoms1 Onlysigns,nosymptoms(signslimitedto upperlidretraction,stare,lidlag,and proptosisto22mm)2 Softtissueinvolvement(symptomandsign)3 Proptosis>22mm4 Extraocularmuscleinvolvement5 Cornealinvolvement6 Sightloss(opticnerveinvolvement)E.Otherstremorofthehandsandtonguemusclewastingrapidreflexresponsediarrhealiverfunctionwbc,andanemia,vitiligo(白癜风),hairloss

pretibial

myxedema

(胫前粘液性水肿)F.Complicationsa.cardiopathyandheartfailure thyrotoxicosis,arrhythmia,heartenlargementand heartfailure,andalldisappearedaftertreatmentb.Thyrotoxiccrisis symptomsandsignsexaggeratedabruptly precipitatingfactors:infection,trauma,surgery radiationthyroiditis,DKA,parturtion Additionalpictures:arrhythmias,pulmonaryedema, congestiveheartfailure,restlessness,delirium, nausea,vomiting,abdominalpain,apathy,stupor, coma,hypotension,shock,etc.c.hypokalemicperiodicparalysis morecommoninAsia abruptlyparalysiswithhypokalemia precipitatedbydextrose,oralcarbohydrate orvigorousexercise. attackslast7-27hrs. somecompaniedbymyastheniagravis.A.SerumTHandTSHa.FT3andFT4b.TT3andTT4c.rT3d.TSHB.TSHreceptorantibodiesLaboratoryandSpecialExamsC.TRHstimulationtest euthyroidGravesophthalmopathy GDmedicationD.131IuptakeandT3suppressiontestE.pathologicalexamsA.FunctionaldiagnosisGDsuspected:(1)weightloss;(2)slightfever;(3)diarrhea;(4)tachycardia;(5)atrialfibrillation;(6)fatigue;(7)dysmenorrhea;(8)withdifficultincontrolofDM,TB,heartfailure,CHD,liverdiseaseDiagnosisandDifferentialDiagnosisB.TypesFT3、FT4,sTSH(uTSH):hyperthyroidismFT3(orTT3),FT4(TT4)normal,sTSH:T3hyperthyroidismFT4(orTT4),FT3(TT3)normal,sTSH:T4hyperthyroidismFT3andFT4(ab)normal,sTSH:subclinicalhyperthyroidismC.PathogenicdiagnosisTRAb,TgAb,TPOAb,HCG,131Iuptake,TSHA.Generalmanagementrestenough,energyandnutrientssupplement,sedativesforrestlessnessandinsomnia.B.Managementofhyperthyroidisma.medicalantithyroidagents:methylthiouracil(MTU)or propylthiouracil(PTU) 300~600mg/d methimazole(MM)or carbimazole(CMZ) 30~60mg/dTreatmentb.dosageandcourse 1ststage(ca.6wks): fulldosagetocontrolsymptoms 2ndstage(ca.4~8wks): dosagedecreasegradually 1/6dosage/wk 3rdstage(ca1yrormore) PTU50mg(orMM5mg),Qdc.“block-replace”regimens THaddedtopreventionof hypothyroidism.T450µg,Qd.d.drug

withdrawal goitersubsides minimaldosagetomaintaintreatedeffects TSHreturntonormal TSAbnegative normalresponsetoTRHe.drugside-effects primaryandsecondaryfailure agranulocytosis(<1%,within2mos) WBCcount/wkormoC.Radioiodine(131I)a.moreactivethanbefore,more(USA)VSless(Euro)b.contraindications: pregnantthyrotoxicosis youngpeople(<20yrs) severeexophthalmos thyrotoxiccrisis failedtoIuptakedosageshouldbecalculatedbyspecialistC.Complications hypothyroidism radiationthyroiditis thyrotoxiccrisis exaggaratedproptosis(smoking)D.Surgeryindications:failedtoantithyroidalagent hugethyroidorsuspectedwith tumors retrosternalgoitercontraindications:severeproptosis severesystemicdiseases earlyandlatepregnancy thyrotoxicosisnotcontrolledE.Treatmentdecision-makinga.firstly,treatedwithmedicationsforallpatientsb.aftercontrolled,decidedby age runcourseofdisease severity&complications thyroidstates doctor’sexperience patient’swillingsandspecialentitiesF.Specialconcernsa.minimaliodidesupplement,iodo-NaClisnotsuitableforGDb.severeproptosistreatedwithcaution,includingTHsupplementandprednisonec.thyroidcrisistreatedwithNaI,PTU,DXM,andpropranolold.PTUisthetreatmentofchoiceforhyperthyroidisminpregnancy,nevermakesTSH<0.5U/Le.heartfailuretreatedwithdigoxinmaybedangerousinsomecases高敏TSH检测在甲状腺功能诊断及

监测中的意义甲状腺功能异常是临床上常见的一组疾病。有研究表明，高敏TSH在甲状腺功能诊断方面最为敏感。1999年9月~2000年11月在我科实验室所做的5100人次甲状腺功能检查，以了解三项检测指标在甲状腺功能诊断及监测中的意义。

1资料和方法1.1实验对象我科临床诊断为甲亢①的病人及甲亢服药复查的病人共4518份血标本。1.2实验方法标本收集每次抽肘静脉血3ml，离心后取血清置–20℃保存。检测方法FT3，FT4用放免法，药盒由天津协和试剂公司提供，TSH用免放法，药盒由天津协和试剂公司提供。1.3统计学处理率的比较采用X2检验。2结果4518份标本中，FT3、FT4均增高，TSH降低者有1596份，占总数的35.25%；FT3增高，TSH降低，FT4正常者有564份，占总数的12.46%；FT4、FT4正常，仅有TSH降低者有736份，占总数的16.25%；三项结果均正常者有820份，占总数的18.11%；FT3、FT4正常，而TSH升高者有338份，占总数的7.46%；FT3、FT4降低，TSH升高者有46份，占总数的1.02%；FT4降低，TSH升高，FT3正常者有314分，占总数的6.93%；FT4增高，TSH降低，FT3正常者有46份，占总数的1.02%；其他各种组合有29份，占总数的0.64%。2.1在诊断甲亢方面以TSH降低为诊断指标，其阳性率为65.33%②

（2952/4518），以FT3升高为诊断指标，阳性率为47.80%（2160/4518）经X2检验，差异有显著性（P<0.001），说明以TSH降低为诊断指标，阳性率为36.56%（1652/4518），明显低于TSH和FT3的阳性率（均P<0.001），提示在诊断甲亢时，FT4的敏感性最低。2.2在诊断甲低方面以TSH升高为诊断指标，其阳性率为15.45%③

（698/4518），以FT4降低为诊断指标，其阳性率为7.97%（360/4518），明显低于前者（P<0.001）；如以FT3降低为诊断指标，其阳性率为1.02%（46/4518），远低于前二者的阳性率（均P<0.001）。3讨论甲状腺功能异常是一组常见的临床症群，它已成了继溏尿病之后的第二个常见的内分泌疾病，包括有甲状腺机能亢进症、亚临床甲亢、甲状腺机能减退症和亚临床甲减。典型的甲亢或甲减因有其明显的临床症状