內(nèi)分泌總論、甲亢(英文)廖二元課件

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

clinical

specialties.B.Whateasytohandleisthatthegeneral

knowledgeandthe

principles

ofendocrinology

and

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

Structureofhormone-secretingcells

peptide/proteinhormone-secretingcells:hormone-containinggranules

(激素顆粒)

steroidhormone-secretingcells:

lipiddroplet(脂質(zhì)小滴)C.Typesofhormonesecretionendocrine(內(nèi)分泌)paracrine(旁分泌)autocrine(自分泌)intracrine(胞內(nèi)分泌)neurocrine(神經(jīng)分泌)juxtacrine(并鄰分泌)solinocrine(腔分泌)amphicrine(雙重分泌)half-life:peptidesandprotein:minutessteroids:variable,hrsdegradationinliver,kedney,othertissues,orinhormone-secretingcells.E.Hormonedegradationandhalf-lifeA:Biologicalrhythms（生物節(jié)律）milliseconds:nerveimpulse,membraneelectrolytes.minutes:neurotransmittershours:LH,TRH,testosterone,cortisol,GH,prolactin,TSH,etcdays:FSHpeaksweeks:menorrheamonths:T4,1,25-(OH)2D3,pregnancySecretionRhythmsB.Circadianrhythms(晝夜節(jié)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(超短反饋)B:shortfeedback(短反饋)C:positivefeedback(正反饋)D:longnegativefeedback(負(fù)反饋):stimulating;:inhibitoryAnerveimpulses/cytokinesCNShypothalamuspituitaryglandtargetglandDBEndocrineRegulationAxesB.Regulationaxes(調(diào)節(jié)軸)a.hypothalamus-pituitary-thyroid(adrenalcortex,sexualgland)b.GIH/GHRH-GH/GHBP-IGFs/IGFBPS-IGFBP/IGFBPasec.renin-AT-ALDinvolvedinrenin,AT,ALD,ANP,AVP,AM(adrenomedullin,腎上腺髓質(zhì)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,多毛癥)genetics,race,androgen.hypertrichosis:PCOS,congenitaladrenalhyperplasia,Cushingdisease,ovariantumors,hypothyroidism,drugs.hairloss:cortisol,androgen,g.gynecomastia(男性乳腺發(fā)育):Klinefeltersyndrome,testiculartumors,drugs.)h.exophthalmos(突眼)：Gravesdisease,chroniclymphocyticthyroiditis,eyediseases.)i.bonepainandfractures(osteoporosis,hyperparathyroidisim,boneorhematologicdiseases)C.Dynemictests(動態(tài)試驗)stimulationtest(興奮試驗)：hypofunction(hypocortisolism)inhibitorystates(TSHinGD)suppressiontest(抑制試驗)：hyperfunction(DXMforCushingdisease)therapeutictest(治療試驗):(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(多結(jié)節(jié)性毒性甲狀腺腫) Plummerdisease(toxicthyroidadenoma) automatichyperfunctionalthyroidnodules(自主功能性甲狀腺結(jié)節(jié)) multipleautoimuneendocrinesyndromewith hyperthyroidism(多發(fā)性自身免疫性內(nèi)分泌腺病伴甲亢) thyroidcarcinomas neonatalhyperthyroidism genetictoxicthyroidhyperplasia/goiter iodine-inducedhyperthyroidism(碘甲亢)PathogenesisofHyperthyroidismPituitaryoriginpituitaryTSHomathyroidhormoneinsensitivitysyndrome(pituitarytype,垂體型TH不敏感綜合征)paracarcinomasyndromeHCG-relatedhyperthyroidismcarcinomas(lung,GI,pancreas)withhyperthyroidismOvariangoiterwithhyperthyroidismIatrogenichyperthyroidism(醫(yī)源性甲亢)TransienthyperthyroidismSubacutedeQuervianthyroiditis(肉芽腫性甲狀腺炎)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(透明質(zhì)酸),chondroitinsulfates(硫酸軟骨素)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(白癜風(fēng)),hairloss

pretibial

myxedema

(脛前粘液性水腫)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檢測在甲狀腺功能診斷及

監(jiān)測中的意義甲狀腺功能異常是臨床上常見的一組疾病。有研究表明，高敏TSH在甲狀腺功能診斷方面最為敏感。1999年9月~2000年11月在我科實驗室所做的5100人次甲狀腺功能檢查，以了解三項檢測指標(biāo)在甲狀腺功能診斷及監(jiān)測中的意義。

1資料和方法1.1實驗對象我科臨床診斷為甲亢①的病人及甲亢服藥復(fù)查的病人共4518份血標(biāo)本。1.2實驗方法標(biāo)本收集每次抽肘靜脈血3ml，離心后取血清置–20℃保存。檢測方法FT3，F(xiàn)T4用放免法，藥盒由天津協(xié)和試劑公司提供，TSH用免放法，藥盒由天津協(xié)和試劑公司提供。1.3統(tǒng)計學(xué)處理率的比較采用X2檢驗。2結(jié)果4518份標(biāo)本中，F(xiàn)T3、FT4均增高，TSH降低者有1596份，占總數(shù)的35.25%；FT3增高，TSH降低，F(xiàn)T4正常者有564份，占總數(shù)的12.46%；FT4、FT4正常，僅有TSH降低者有736份，占總數(shù)的16.25%；三項結(jié)果均正常者有820份，占總數(shù)的18.11%；FT3、FT4正常，而TSH升高者有338份，占總數(shù)的7.46%；FT3、FT4降低，TSH升高者有46份，占總數(shù)的1.02%；FT4降低，TSH升高，F(xiàn)T3正常者有314分，占總數(shù)的6.93%；FT4增高，TSH降低，F(xiàn)T3正常者有46份，占總數(shù)的1.02%；其他各種組合有29份，占總數(shù)的0.64%。2.1在診斷甲亢方面以TSH降低為診斷指標(biāo)，其陽性率為65.33%②

（2952/4518），以FT3升高為診斷指標(biāo)，陽性率為47.80%（2160/4518）經(jīng)X2檢驗，差異有顯著性（P<0.001），說明以TSH降低為診斷指標(biāo)，陽性率為36.56%（1652/4518），明顯低于TSH和FT3的陽性率（均P<0.001），提示在診斷甲亢時，F(xiàn)T4的敏感性最低。2.2在診斷甲低方面以TSH升高為診斷指標(biāo)，其陽性率為15.45%③

（698/4518），以FT4降低為診斷指標(biāo)，其陽性率為7.97%（360/4518），明顯低于前者（P<0.001）；如以FT3降低為診斷指標(biāo)，其陽性率為1.02%（46/4518），遠(yuǎn)低于前二者的陽性率（均P<0.001）。3討論甲狀腺功能異常是一組常見的臨床癥群，它已成了繼溏尿病之后的第二個常見的內(nèi)分泌疾病，包括有甲狀腺機(jī)能亢進(jìn)癥、亞臨床甲亢、甲狀腺機(jī)能減退癥和亞臨床甲減。典型的甲亢或甲減因有其明顯的臨床癥狀