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内分泌总论甲亢英文廖二元第1页,课件共72页,创作于2023年2月A.Therapidityandextensivenessofadvancesinendocrinologyhavemadeitincreasinglydifficultforthestudentsandphysicianstotakefulladvantageofinformationavailablefortheunderstanding,diagnosis,andtreatmentofclinicaldisorders,notonlyofdiseasesinendocrinology,butalsoofthatinall
clinical
specialties.第2页,课件共72页,创作于2023年2月B.Whateasytohandleisthatthegeneral
knowledgeandthe
principles
ofendocrinology
and
metabolism.C.Forinterest,beinterestedintheinterestingmedicalbranch.D.Mainsubjects第3页,课件共72页,创作于2023年2月RegulationsystemsofextracellularcommunicationEndocrineglandandhormone-secretingcellsHormonesHormonesecretionrhythmsHormonesynthasesanditsregulationEndocrineregulationaxes第4页,课件共72页,创作于2023年2月MechanismsofhormoneactionNutrientmetabolismSystemicexaminationLaboratoryandspecialexaminationsTherapeuticprinciples第5页,课件共72页,创作于2023年2月RegulationSystemsofExtra-CellularCommunicationnervoussystemendocrinesystemimmunesystem第6页,课件共72页,创作于2023年2月EndocrineGlandandHormone-SecretingCells(激素分泌细胞)A.Endocrineglanda.hypothalamus&posteriorpituitaryb.pinealgland(松果体)c.anteriorandintermedialpituitary第7页,课件共72页,创作于2023年2月d.thyroide.parathyroidf.endocrinepancreas(内分泌胰腺)g.adrenalcortexandmedullah.sexualgland(testisorovary)i.others:thymus(胸腺),placenta第8页,课件共72页,创作于2023年2月B.Diffuseneuro-endocrinecellsAPUD(amineprecursoruptakeanddecarboxylation)cellsinGI,pancreas,adrenalmedulla,etc.)C.Hormone-secretingcellsintissuesatrium,endothelium,fibroblast,lipocytes,lymphocytes第9页,课件共72页,创作于2023年2月Structureofhormone-secretingcells
peptide/proteinhormone-secretingcells:hormone-containinggranules
(激素颗粒)steroidhormone-secretingcells:lipiddroplet(脂质小滴)第10页,课件共72页,创作于2023年2月A.Classificationa.aspeptide/proteinb.asderivativesofaminoacid(catecholamine,5-HT,melatonin,T3/T4)c.asderivatesofcholesterol(cortisol,aldosterone,estrogen,androgen,progesterone,1,25-(OH)2D3)B.Storagehormonegranulesthyroglobulin(甲状腺球蛋白)Hormones第11页,课件共72页,创作于2023年2月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)第12页,课件共72页,创作于2023年2月solublehormone+bindingprotein:insulin,GH.IGF.Glucagon-likepeptideinsolublehormone+bindingprotein:T3,T4,sexsteroids,cortisol,vitaminD.D.Hormonetransportation第13页,课件共72页,创作于2023年2月half-life:peptidesandprotein:minutessteroids:variable,hrsdegradationinliver,kedney,othertissues,orinhormone-secretingcells.E.Hormonedegradationandhalf-life第14页,课件共72页,创作于2023年2月A: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,pregnancySecretionRhythms第15页,课件共72页,创作于2023年2月B.Circadianrhythms(昼夜节律)biological“clock”inhypothalamus(melatonin),butlostinCushingdiseaseandpsychosisC.24-hrchangesofserumandurinehormone(metabolicproducts)第16页,课件共72页,创作于2023年2月D.Heterogeneityofserumhormoneshormone,pro-hormone(激素原),prepro-hormone(前激素原)monomer,dimer,trimertetramer,etc.fragementofpeptides.第17页,课件共72页,创作于2023年2月A.Endocrineregulationactivehormonemoleculehormone-bindingproteinhormonereceptoronmembraneincytoplasmainnucleolus(nucleoplasm)post-receptortransduction(cascadereaction)tropic-hormone(促激素)feedbackcycletargetcellreactionHormoneSynthasesandItsRegulation第18页,课件共72页,创作于2023年2月B.Paracrine/autocrineregulationexistalmostinalltissues.“point-line”(点-线式)regulationnetwork第19页,课件共72页,创作于2023年2月A.HormoneregulationA:ultra-shortfeedback(超短反馈)B:shortfeedback(短反馈)C:positivefeedback(正反馈)D:longnegativefeedback(负反馈):stimulating;:inhibitoryAnerveimpulses/cytokinesCNShypothalamuspituitaryglandtargetglandDBEndocrineRegulationAxes第20页,课件共72页,创作于2023年2月B.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)第21页,课件共72页,创作于2023年2月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22页,课件共72页,创作于2023年2月A.Actedastranscription-regulatoryfactorssteroidhormonebindinwithreceptor(cytoplasmornucleoplasm)H-Rcomplex+DNAbindingdomaingeneexpressionproteinMechanismsofHormoneAction第23页,课件共72页,创作于2023年2月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24页,课件共72页,创作于2023年2月metabolism,anabolismandcatabolismmetabolicdiseases(relatedtoenzymes,hormones,orionchannels,etc).macroelementandmicroelement(tracedelement)micronutrient(Fe,F,Zn,Cu,Mn,I,Cr,Co,etc)vitaminsNutrientMetabolismA.Generalconcepts:第25页,课件共72页,创作于2023年2月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26页,课件共72页,创作于2023年2月d.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.第27页,课件共72页,创作于2023年2月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)第28页,课件共72页,创作于2023年2月A.hormonesandbiomarkers(生化标志物)inserumandurine:hormones,electrolytes,sugarB.hormonederivatives:VMA,17-OHCS,17-KSLaboratoryandSpecialExaminations第29页,课件共72页,创作于2023年2月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)第30页,课件共72页,创作于2023年2月provocationtest(glucagontestfordiagnosisofpheochromocytoma)X-rayfilm(bonediseases,kedneystones)CT&MRI(morphologicchanges)radionucleartomography(thyroid,pancreas,adrenalcortexandmedulla,parathyroid,etc)typeBUS(thyroid,adrenalcortex,ovary,testis)第31页,课件共72页,创作于2023年2月A.Pathogenictherapy:supplementofnutrients,genetreatment.B.Hypofunction:1.hormonereplacementtherapy(Addisondisease,hypothyroidism;hypogonadism)2.drugstostimulatehormonesecretion(sulfonylureafortype2DM)3.transplantation(organ,tissue,cells)TherapeuticPrinciples第32页,课件共72页,创作于2023年2月C.Hyperfunction1.drugstosuppresshormonesecretion(iodideforGD,spironolactoneforhyperaldosteronism.SSforinsulinoma)2.radioactivetherapy(131IforGD,γ-knifeforpituitarytumors)第33页,课件共72页,创作于2023年2月HYPERTHYROIDISM(THYROTOXICOSIS,甲亢)Hyperthyroidismisonlyadiagnosisofexcessivethyroidhormonestatus,notaconcretediseaseorasyndrome.Itiswrongtosay“Gravesdisease(Graves病)”as“hyperthyroidism(甲亢)”inbrief.第34页,课件共72页,创作于2023年2月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)PathogenesisofHyperthyroidism第35页,课件共72页,创作于2023年2月PituitaryoriginpituitaryTSHomathyroidhormoneinsensitivitysyndrome(pituitarytype,垂体型TH不敏感综合征)paracarcinomasyndromeHCG-relatedhyperthyroidismcarcinomas(lung,GI,pancreas)withhyperthyroidismOvariangoiterwithhyperthyroidismIatrogenichyperthyroidism(医源性甲亢)第36页,课件共72页,创作于2023年2月TransienthyperthyroidismSubacutedeQuervianthyroiditis(肉芽肿性甲状腺炎)hymphocyticthyroiditis(postpartum,IFN,IL,Li)trumaticthyroiditisradioactivethyroiditisChronicchroniclymphocyticthyroiditis第37页,课件共72页,创作于2023年2月PathogenesisHistopathologyClinicalpresentationLaboratoryandspecialexamsDiagnosisanddifferentialdiagnosisTreatmentGRAVESDISEASE(GD)第38页,课件共72页,创作于2023年2月GDisalsocalled:diffusetoxicgoiter BasedowdiseaseSubclinicalhyperthyroidismisusuallyreferredtoaGDstatewith(ab)normalT3,T4,decreasedTSH,andnoclinicalsymptomsofhyperthyroidismGravesDisease(GD)第39页,课件共72页,创作于2023年2月A.Abnormalitiesofimmunesystema.TSH-R-Ab+TSH-RmimictheactionofTSHhyperfunctionandgoiter.b.functioningofIgThhypersensitivity+IL-1,IL-2BcellsproduceTSH-R-Ab(TRAb)Pathogenesis第40页,课件共72页,创作于2023年2月 stimulatingIgGhyperfunction(TSAb)c.TRAb inhibitoryIgGhypofunctionandantagonist ofTSHRand TSAb(TF1Ab,TGBAb) growth-stimulatingIgG(TGI)B.Otherfactorsgeneticfactorsinfectivefactorsstress(physicaloremotional)第41页,课件共72页,创作于2023年2月C.Thyroid-associatedophthalmopathy(TAO)unknownGAG(葡萄聚糖)accumulation,Tcellinfiltration,edema,fibrosisandsightloss.第42页,课件共72页,创作于2023年2月A.Thyroidgoiter:symmetrical,diffuse,softenlargedaftertreatment:lobularfollicles:hyperplasticcolumnwithscantcolloid,papillaryprojections,vascularityincreasedlymphocytesandplasmacellsinfiltrationHistopathology第43页,课件共72页,创作于2023年2月B.Eyesorbitalcontentsincreased,containingmucoprotein,GAG(glycosaminoglycan,葡糖聚糖),lymphocytes.C.Skin(dermopathy)hyaluronicacid(透明质酸),chondroitinsulfates(硫酸软骨素)increased,collagenfibersseparatednodularandplaqueformationlymphaticdrainagedecreased第44页,课件共72页,创作于2023年2月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45页,课件共72页,创作于2023年2月C.Thyroiddiffusegoiter:absentintheelderly,consistency:soft,firm,rubbery,symmetricalenlarged,surface:smooth,lobular,thrillwithaudible
bruit
eyelidspasmorretraction第46页,课件共72页,创作于2023年2月D.
Eyesa.non-infiltrativeorbitopathy:fissurewidened,scleraexposed,lidretraction,lidtremor,lidlay,globelay.第47页,课件共72页,创作于2023年2月b.infiltrative
orbitopathy: excessivetearing exophthalmos(asymmetrical) eyelidsunclosed blurredvision doublevision visualacuitydecreased corneasulcerated,infected sightloss第48页,课件共72页,创作于2023年2月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49页,课件共72页,创作于2023年2月E.Otherstremorofthehandsandtonguemusclewastingrapidreflexresponsediarrhealiverfunctionwbc,andanemia,vitiligo(白癜风),hairloss
pretibial
myxedema
(胫前粘液性水肿)第50页,课件共72页,创作于2023年2月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51页,课件共72页,创作于2023年2月c.hypokalemicperiodicparalysis morecommoninAsia abruptlyparalysiswithhypokalemia precipitatedbydextrose,oralcarbohydrate orvigorousexercise. attackslast7-27hrs. somecompaniedbymyastheniagravis.第52页,课件共72页,创作于2023年2月A.SerumTHandTSHa.FT3andFT4b.TT3andTT4c.rT3d.TSHB.TSHreceptorantibodiesLaboratoryandSpecialExams第53页,课件共72页,创作于2023年2月C.TRHstimulationtest euthyroidGravesophthalmopathy GDmedicationD.131IuptakeandT3suppressiontestE.pathologicalexams第54页,课件共72页,创作于2023年2月A.FunctionaldiagnosisGDsuspected:(1)weightloss;(2)slightfever;(3)diarrhea;(4)tachycardia;(5)atrialfibrillation;(6)fatigue;(7)dysmenorrhea;(8)withdifficultincontrolofDM,TB,heartfailure,CHD,liverdiseaseDiagnosisandDifferentialDiagnosis第55页,课件共72页,创作于2023年2月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56页,课件共72页,创作于2023年2月A.Generalmanagementrestenough,energyandnutrientssupplement,sedativesforrestlessnessandinsomnia.B.Managementofhyperthyroidisma.medicalantithyroidagents:methylthiouracil(MTU)or propylthiouracil(PTU) 300~600mg/d methimazole(MM)or carbimazole(CMZ) 30~60mg/dTreatment第57页,课件共72页,创作于2023年2月b.dosageandcourse 1ststage(ca.6wks): fulldosagetocontrolsymptoms 2ndstage(ca.4~8wks): dosagedecreasegradually 1/6dosage/wk 3rdstage(ca1yrormore) PTU50mg(orMM5mg),Qd第58页,课件共72页,创作于2023年2月c.“block-replace”regimens THaddedtopreventionof hypothyroidism.T450µg,Qd.d.drug
withdrawal goitersubsides minimaldosagetomaintaintreatedeffects TSHreturntonormal TSAbnegative normalresponsetoTRH第59页,课件共72页,创作于2023年2月e.drugside-effects primaryandsecondaryfailure agranulocytosis(<1%,within2mos) WBCcount/wkormo第60页,课件共72页,创作于2023年2月C.Radioiodine(131I)a.moreactivethanbefore,more(USA)VSless(Euro)b.contraindications: pregnantthyrotoxicosis youngpeople(<20yrs) severeexophthalmos thyrotoxiccrisis failedtoIuptakedosageshouldbecalculatedbyspecialist第61页,课件共72页,创作于2023年2月C.Complications hypothyroidism radiationthyroiditis thyrotoxiccrisis exaggaratedproptosis(smoking)第62页,课件共72页,创作于2023年2月D.Surgeryindications:failedtoantithyroidalagent hugethyroidorsuspectedwith tumors retrosternalgoitercontraindications:severeproptosis severesystemicdiseases earlyandlatepregnancy thyrotoxicosisnotcontrolled第63页,课件共72页,创作于2023年2月E.Treatmentdecision-makinga.firstly,treatedwithmedicationsforallpatientsb.aftercontrolled,decidedby age runcourseofdisease severity&complications thyroidstates doctor’sexperience patient’swillingsandspecialentities第64页,课件共72页,创作于2023年2月F.Specialconcernsa.minimaliodidesupplement,iodo-NaClisnotsuitableforGDb.severeproptosistreatedwithcaution,includingTHsupplementandprednisonec.thyroidcrisistreatedwithNaI,PTU,DXM,andpropranolol第65页,课件共72页,创作于2023年2月d.PTUisthetreatmentofchoiceforhyperthyroidisminpregnancy,nevermakesTSH<0.5U/Le.heartfailuretreatedwithdigoxinmaybedangerousinsomecases第66页,课件共72页,创作于2023年2月高敏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。第67页,课件共72页,创作于2023年2月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
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