內(nèi)分泌總論甲亢英文廖二元

B.Whateasytohandleisthatthegeneral

knowledgeandthe

principles

ofendocrinology

and

metabolism.C.Forinterest,beinterestedintheinterestingmedicalbranch.D.Mainsubjects第一頁第二頁，共71頁。RegulationsystemsofextracellularcommunicationEndocrineglandandhormone-secretingcellsHormonesHormonesecretionrhythmsHormonesynthasesanditsregulationEndocrineregulationaxes第二頁第三頁，共71頁。MechanismsofhormoneactionNutrientmetabolismSystemicexaminationLaboratoryandspecialexaminationsTherapeuticprinciples第三頁第四頁，共71頁。RegulationSystemsofExtra-CellularCommunicationnervoussystemendocrinesystemimmunesystem第四頁第五頁，共71頁。EndocrineGlandandHormone-SecretingCells（激素分泌細(xì)胞）A.Endocrineglanda.hypothalamus&posteriorpituitaryb.pinealgland(松果體)c.anteriorandintermedialpituitary第五頁第六頁，共71頁。d.thyroide.parathyroidf.endocrinepancreas(內(nèi)分泌胰腺)g.adrenalcortexandmedullah.sexualgland(testisorovary)i.others:thymus(胸腺)，placenta第六頁第七頁，共71頁。B.Diffuseneuro-endocrinecellsAPUD(amineprecursoruptakeanddecarboxylation)cellsinGI,pancreas,adrenalmedulla,etc.)C.Hormone-secretingcellsintissuesatrium,endothelium,fibroblast,lipocytes,lymphocytes第七頁第八頁，共71頁。Structureofhormone-secretingcellspeptide/proteinhormone-secretingcells:hormone-containinggranules

(激素顆粒)steroidhormone-secretingcells:lipiddroplet(脂質(zhì)小滴)第八頁第九頁，共71頁。A.Classificationa.aspeptide/proteinb.asderivativesofaminoacid(catecholamine,5-HT,melatonin,T3/T4)c.asderivatesofcholesterol(cortisol,aldosterone,estrogen,androgen,progesterone,1,25-(OH)2D3)B.Storagehormonegranulesthyroglobulin(甲狀腺球蛋白)Hormones第九頁第十頁，共71頁。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)第十頁第十一頁，共71頁。solublehormone+bindingprotein:insulin,GH.IGF.Glucagon-likepeptideinsolublehormone+bindingprotein:T3,T4,sexsteroids,cortisol,vitaminD.D.Hormonetransportation第十一頁第十二頁，共71頁。half-life:peptidesandprotein:minutessteroids:variable,hrsdegradationinliver,kedney,othertissues,orinhormone-secretingcells.E.Hormonedegradationandhalf-life第十二頁第十三頁，共71頁。A: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,pregnancySecretionRhythms第十三頁第十四頁，共71頁。B.Circadianrhythms(晝夜節(jié)律)biological“clock”inhypothalamus(melatonin),butlostinCushingdiseaseandpsychosisC.24-hrchangesofserumandurinehormone(metabolicproducts)第十四頁第十五頁，共71頁。D.Heterogeneityofserumhormoneshormone,pro-hormone(激素原),prepro-hormone(前激素原)monomer,dimer,trimertetramer,etc.fragementofpeptides.第十五頁第十六頁，共71頁。A.Endocrineregulationactivehormonemoleculehormone-bindingproteinhormonereceptoronmembraneincytoplasmainnucleolus(nucleoplasm)post-receptortransduction(cascadereaction)tropic-hormone(促激素)feedbackcycletargetcellreactionHormoneSynthasesandItsRegulation第十六頁第十七頁，共71頁。B.Paracrine/autocrineregulationexistalmostinalltissues.“point-line”(點-線式)regulationnetwork第十七頁第十八頁，共71頁。A.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/cytokinesCNShypothalamuspituitaryglandtargetglandDBEndocrineRegulationAxes第十八頁第十九頁，共71頁。B.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)第十九頁第二十頁，共71頁。d.axisofendocrinepancreas-energymetabolismandbodyweightinvolvedininsulin,glucagon,glucagon-likepeptide-1,somatostatin,leptin,etc.e.PTH-CT-1,25-(OH)2D3involvedinPTH,CT,1,25-(OH)2D3,serumCa2+,Pi3-f.AVP-AVPreceptor-AQP(aquaporin,水孔蛋白)V1receptor:relatedtoregulationofBPV2receptor:relatedtoH2Oreabsorption第二十頁第二十一頁，共71頁。A.Actedastranscription-regulatoryfactorssteroidhormonebindinwithreceptor(cytoplasmornucleoplasm)H-Rcomplex+DNAbindingdomaingeneexpressionproteinMechanismsofHormoneAction第二十一頁第二十二頁，共71頁。B.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.第二十二頁第二十三頁，共71頁。metabolism,anabolismandcatabolismmetabolicdiseases(relatedtoenzymes,hormones,orionchannels,etc).macroelementandmicroelement(tracedelement)micronutrient(Fe,F,Zn,Cu,Mn,I,Cr,Co,etc)vitaminsNutrientMetabolismA.Generalconcepts:第二十三頁第二十四頁，共71頁。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)SystemicExamination第二十四頁第二十五頁，共71頁。d.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.第二十五頁第二十六頁，共71頁。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)第二十六頁第二十七頁，共71頁。A.hormonesandbiomarkers(生化標(biāo)志物)inserumandurine:hormones,electrolytes,sugarB.hormonederivatives:VMA,17-OHCS,17-KSLaboratoryandSpecialExaminations第二十七頁第二十八頁，共71頁。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)第二十八頁第二十九頁，共71頁。provocationtest(glucagontestfordiagnosisofpheochromocytoma)X-rayfilm(bonediseases,kedneystones)CT&MRI(morphologicchanges)radionucleartomography(thyroid,pancreas,adrenalcortexandmedulla,parathyroid,etc)typeBUS(thyroid,adrenalcortex,ovary,testis)第二十九頁第三十頁，共71頁。A.Pathogenictherapy:supplementofnutrients,genetreatment.B.Hypofunction:1.hormonereplacementtherapy(Addisondisease,hypothyroidism;hypogonadism)2.drugstostimulatehormonesecretion(sulfonylureafortype2DM)3.transplantation(organ,tissue,cells)TherapeuticPrinciples第三十頁第三十一頁，共71頁。C.Hyperfunction1.drugstosuppresshormonesecretion(iodideforGD,spironolactoneforhyperaldosteronism.SSforinsulinoma)2.radioactivetherapy(131IforGD,γ-knifeforpituitarytumors)第三十一頁第三十二頁，共71頁。HYPERTHYROIDISM(THYROTOXICOSIS,甲亢)Hyperthyroidismisonlyadiagnosisofexcessivethyroidhormonestatus,notaconcretediseaseorasyndrome.Itiswrongtosay“Gravesdisease(Graves病)”as“hyperthyroidism(甲亢)”inbrief.第三十二頁第三十三頁，共71頁。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)PathogenesisofHyperthyroidism第三十三頁第三十四頁，共71頁。PituitaryoriginpituitaryTSHomathyroidhormoneinsensitivitysyndrome(pituitarytype,垂體型TH不敏感綜合征)paracarcinomasyndromeHCG-relatedhyperthyroidismcarcinomas(lung,GI,pancreas)withhyperthyroidismOvariangoiterwithhyperthyroidismIatrogenichyperthyroidism(醫(yī)源性甲亢)第三十四頁第三十五頁，共71頁。TransienthyperthyroidismSubacutedeQuervianthyroiditis(肉芽腫性甲狀腺炎)hymphocyticthyroiditis(postpartum,IFN,IL,Li)trumaticthyroiditisradioactivethyroiditisChronicchroniclymphocyticthyroiditis第三十五頁第三十六頁，共71頁。PathogenesisHistopathologyClinicalpresentationLaboratoryandspecialexamsDiagnosisanddifferentialdiagnosisTreatmentGRAVESDISEASE(GD)第三十六頁第三十七頁，共71頁。GDisalsocalled:diffusetoxicgoiter BasedowdiseaseSubclinicalhyperthyroidismisusuallyreferredtoaGDstatewith(ab)normalT3,T4,decreasedTSH,andnoclinicalsymptomsofhyperthyroidismGravesDisease(GD)第三十七頁第三十八頁，共71頁。A.Abnormalitiesofimmunesystema.TSH-R-Ab+TSH-RmimictheactionofTSHhyperfunctionandgoiter.b.functioningofIgThhypersensitivity+IL-1,IL-2BcellsproduceTSH-R-Ab(TRAb)Pathogenesis第三十八頁第三十九頁，共71頁。 stimulatingIgGhyperfunction(TSAb)c.TRAb inhibitoryIgGhypofunctionandantagonist ofTSHRand TSAb(TF1Ab,TGBAb) growth-stimulatingIgG(TGI)B.Otherfactorsgeneticfactorsinfectivefactorsstress(physicaloremotional)第三十九頁第四十頁，共71頁。C.Thyroid-associatedophthalmopathy(TAO)unknownGAG(葡萄聚糖)accumulation,Tcellinfiltration,edema,fibrosisandsightloss.第四十頁第四十一頁，共71頁。A.Thyroidgoiter:symmetrical,diffuse,softenlargedaftertreatment:lobularfollicles:hyperplasticcolumnwithscantcolloid,papillaryprojections,vascularityincreasedlymphocytesandplasmacellsinfiltrationHistopathology第四十一頁第四十二頁，共71頁。B.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,collagenfibersseparatednodularandplaqueformationlymphaticdrainagedecreased第四十二頁第四十三頁，共71頁。A.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%)ClinicalPresentation第四十三頁第四十四頁，共71頁。C.Thyroiddiffusegoiter:absentintheelderly,consistency:soft,firm,rubbery,symmetricalenlarged,surface:smooth,lobular,thrillwithaudible

bruit

eyelidspasmorretraction第四十四頁第四十五頁，共71頁。D.

Eyesa.non-infiltrativeorbitopathy:fissurewidened,scleraexposed,lidretraction,lidtremor,lidlay,globelay.第四十五頁第四十六頁，共71頁。b.infiltrative

orbitopathy: excessivetearing exophthalmos(asymmetrical) eyelidsunclosed blurredvision doublevision visualacuitydecreased corneasulcerated,infected sightloss第四十六頁第四十七頁，共71頁。c.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)第四十七頁第四十八頁，共71頁。E.Otherstremorofthehandsandtonguemusclewastingrapidreflexresponsediarrhealiverfunctionwbc,andanemia,vitiligo(白癜風(fēng)),hairloss

pretibial

myxedema

(脛前粘液性水腫)第四十八頁第四十九頁，共71頁。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.第四十九頁第五十頁，共71頁。c.hypokalemicperiodicparalysis morecommoninAsia abruptlyparalysiswithhypokalemia precipitatedbydextrose,oralcarbohydrate orvigorousexercise. attackslast7-27hrs. somecompaniedbymyastheniagravis.第五十頁第五十一頁，共71頁。A.SerumTHandTSHa.FT3andFT4b.TT3andTT4c.rT3d.TSHB.TSHreceptorantibodiesLaboratoryandSpecialExams第五十一頁第五十二頁，共71頁。C.TRHstimulationtest euthyroidGravesophthalmopathy GDmedicationD.131IuptakeandT3suppressiontestE.pathologicalexams第五十二頁第五十三頁，共71頁。A.FunctionaldiagnosisGDsuspected:(1)weightloss;(2)slightfever;(3)diarrhea;(4)tachycardia;(5)atrialfibrillation;(6)fatigue;(7)dysmenorrhea;(8)withdifficultincontrolofDM,TB,heartfailure,CHD,liverdiseaseDiagnosisandDifferentialDiagnosis第五十三頁第五十四頁，共71頁。B.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,TSH第五十四頁第五十五頁，共71頁。A.Generalmanagementrestenough,energyandnutrientssupplement,sedativesforrestlessnessandinsomnia.B.Managementofhyperthyroidisma.medicalantithyroidagents:methylthiouracil(MTU)or propylthiouracil(PTU) 300~600mg/d methimazole(MM)or carbimazole(CMZ) 30~60mg/dTreatment第五十五頁第五十六頁，共71頁。b.dosageandcourse 1ststage(ca.6wks): fulldosagetocontrolsymptoms 2ndstage(ca.4~8wks): dosagedecreasegradually 1/6dosage/wk 3rdstage(ca1yrormore) PTU50mg(orMM5mg),Qd第五十六頁第五十七頁，共71頁。c.“block-replace”regimens THaddedtopreventionof hypothyroidism.T450μg,Qd.d.drug

withdrawal goitersubsides minimaldosagetomaintaintreatedeffects TSHreturntonormal TSAbnegative normalresponsetoTRH第五十七頁第五十八頁，共71頁。e.drugside-effects primaryandsecondaryfailure agranulocytosis(<1%,within2mos) WBCcount/wkormo第五十八頁第五十九頁，共71頁。C.Radioiodine(131I)a.moreactivethanbefore,more(USA)VSless(Euro)b.contraindications: pregnantthyrotoxicosis youngpeople(<20yrs) severeexophthalmos thyrotoxiccrisis failedtoIuptakedosageshouldbecalculatedbyspecialist第五十九頁第六十頁，共71頁。C.Complications hypothyroidism radiationthyroiditis thyrotoxiccrisis exaggaratedproptosis(smoking)第六十頁第六十一頁，共71頁。D.Surgeryindications:failedtoantithyroidalagent hugethyroidorsuspectedwith tumors retrosternalgoitercontraindications:severeproptosis severesystemicdiseases earlyandlatepregnancy thyrotoxicosisnotcontrolled第六十一頁第六十二頁，共71頁。E.Treatmentdecision-makinga.firstly,treatedwithmedicationsforallpatientsb.aftercontrolled,decidedby age runcourseofdisease severity&complications thyroidstates doctor’sexperience patient’swillingsandspecialentities第六十二頁第六十三頁，共71頁。F.Specialconcernsa.minimaliodidesupplement,iodo-NaClisnotsuitableforGDb.severeproptosistreatedwithcaution,includingTHsupplementandprednisonec.thyroidcrisistreatedwithNaI,PTU,DXM,andpropranolol第六十三頁第六十四頁，共71頁。d.PTUisthetreatmentofchoiceforhyperthyroidisminpregnancy,nevermakesTSH<0.5U/Le.heartfailuretreatedwithdigoxinmaybedangerousinsomecases第六十四頁第六十五頁，共71頁。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