高鑫-内分泌总论

1内分泌系统疾病总论IntroductiontoEndocrinologyandMetabolicDiseases复旦大学附属中山医院内分泌科高鑫2HistoryanddevelopmentofEndocrinology(1)Roughlyahundredyearsago,Starlingcoinedthetermhormonetodescribesecretin,asubstancesecretedbythesmallintestineintothebloodstreamtostimulatepancreaticsecretion.InhisCroonianLectures,Starlingconsideredtheendo-crineandnervoussystemsastwodistinctmechanismsforcoordinationandcontroloforganfunction.Thus,endocrinologyfounditsfirsthomeinthedisciplineofmammalianphysiology.3Workoverthenextseveraldecadesbybiochemists,physiologists,andclinicalinvestigatorsledtothecharacterizationofmanyhormonessecretedintothebloodstreamfromdiscreteglandsorotherorgans.Theseinvestigatorsshowedforthefirsttimethatdiseasessuchashypothyroidismanddiabetescouldbetreatedsuccessfullybyreplacingspecifichormones.Theseinitialtriumphsformedthefoundationoftheclinicalspecialtyofendocrinology.HistoryanddevelopmentofEndocrinology(2)4Advancesincellbiology,molecularbiology,andgeneticsovertheensuingyearsbegantohelpexplainthemechanismsofendocrinediseasesandofhormonesecretionandaction.Althoughtheseadvanceshaveembeddedendocrinologyintotheframeworkofmolecularcellbiology,theyhavenotchangedtheessentialsubjectofendocrinology_____thesignalingthatcoordinatesandcontrolsthefunctionsofmultipleorgansandprocesses.HistoryanddevelopmentofEndocrinology(2)5Hormoneformationmayoccureitherinlocalizedcollectionsofspecificcells,intheendocrineglands,orincellsthathaveadditionalroles.Manyproteinhormones:growthhormone?parathyroidhormone?prolactin?insulin?glucagon?Leptin?FormationofsmallhormonemoleculesinitiateswithcommonlyfoundPrecursors:Suchas:adrenals,gonads,orthyroid.Inthecaseofthesteroidhormones,theprecursorischolesterol,whichismodifiedbyvarioushydroxylations,methylations,anddemethylationstoformtheglucocorticoids,androgens,andestrogens.Incontrast,theprecursorofvitaminD,7-dehydrocholesterol,isproducedinskinkeratinocytes,againfromcholesterol,byaphotochemicalreaction.ENDOCRINEGLANDS6内分泌系统内分泌腺脏器内分泌组织激素体液调节系统（包括旁分泌、自分泌）代谢过程脏器功能生长发育生殖衰老EndocrineSystem7内分泌学发展三阶段腺体内分泌学OrganicEndocrinology组织内分泌学HistologicalEndocrinology分子内分泌学MoleculerEndocrinology8激素的种类Hormones肽类/蛋白类激素（Proteinorpeptide):ACTH,LH,FSH,PHT,TSH,Insulun,Glucagon,IGFs氨基酸衍生物（AminoAcidderivatives)：儿茶酚胺类（肾上腺素、去甲肾上腺素）脂肪酸衍生物(Fattyacidderivatives):前列腺素类、视黄酸胆固醇衍生物（Cholesterolderivatives)：考的松，醛固酮、1,25(OH)2D3性激素9激素的作用机制（1）与膜受体结合G蛋白偶联发挥生物效应（肽类激素、生物胺、前列腺素）与膜受体结合受体自身磷酸化发挥生物学效应（酪氨酸激酶）（生长因子家族、Insulin,IGFs)与核受体结合与DNA特异序列结合功能蛋白转录（甾体类激素）1011G-protein-coupled7-membranespanningreceptor12G-protein-coupled7-membranespanningreceptor13141516激素的作用机制（2）激素信息在细胞内的信号传导Coris:发现了磷酸化酶的可逆磷酸化（无活性的磷酸化酶b/有活性的磷酸化酶a之间的互变）获得1951年诺贝尔奖。Sutherland:成功分离和确定的腺苷酸环化酶和磷酸二酯酶（cAMP合成与分解的两个关键酶）提出了激素作用的第二信使学说获得1971年诺贝尔生理医学奖。Krebs&Fisher:于60年代末发现蛋白激酶A(PKA)（依赖cAMP,刺激多种底物蛋白磷酸化)阐明了PKA启动的磷酸化和去磷酸化途径。获得1992年诺贝尔生理医学奖。17内分泌系统的相互调节神经---内分泌系统的相互调节内分泌系统的反馈调节免疫系统与内分泌系统的关系神经-内分泌-免疫网络调节1820内分泌疾病的分类按病变器官分类按功能分类：亢进、减退、正常；按病变部位分类：原发性、继发性、三发性激素分泌缺陷受体基因缺陷---激素抵抗21内分泌疾病的诊断原则三大原则：功能诊断定位诊断病因/病理诊断22内分泌疾病的诊断原则功能诊断症状、体征实验室资料：代谢紊乱的证据；激素分泌异常的证据；内分泌功能试验：兴奋试验抑制试验激发试验同位素检查细胞学检查骨密度检查23内分泌疾病的诊断原则定位诊断同位素显象扫描磁共振CTB超声检查24内分泌疾病的诊断原则病因诊断免疫学检查组织病理学检查细胞学检查染色体检查受体测定分子生物学检查25内分泌疾病的防治原则预防为主：地方性甲状腺肿甲状腺危象肾上腺危象低血糖反应黏液性水肿昏迷26治疗原则病因治疗：垂体瘤、肾上腺腺瘤、嗜铬细胞瘤、甲状旁腺腺瘤等纠正代谢紊乱：腺体功能亢进的治疗；腺体功能减退的治疗；27腺体功能亢进的治疗：手术、放射治疗、抑制激素合成与释放的药物；化疗药物；腺体功能减退的治疗：替代治疗补充生理剂量的激素甲状腺激素、肾上腺皮质激素、生长激素等治疗原则28Howtostudyclinicalendocrinology29TheEndocrinePatientAtextbookofmedicineisinevitablyaboutdisease,butthepracticeofmedicinedealswithillness.Thetopicof“theendocrinepatienttobediscussedinclude:initialevaluation,thenatureofreferral,thefactfindingrequiredinclinicalevaluation,theuseofthelaboratoryandimaging,theformulationofadifferentialdiagnosis,decisionmaking,andmanagement.30Manyfeaturesofbeinganendocrinepatientarecommontoallexperiencesofillness.Afewminutesspentingettingtoknowthepatientcanpayenormousdividendsintheaccuracyofthehistoryobtainedandinsettingthestageforfurthercooperationwithtestingandtreatment.Inasmuchasmostendocrineconsultationiselectiveratherthanemergent,anexperiencedphysicianfavorsaskingafewsimplequestions,suchasWhereareyoufrom?Whatdoyoudo?Howdidyoucometous?Wereyoureferred?andsoon.Almostalways,somecommonexperienceoracquaintanceisdiscoveredthatprovidesthebasisforarapportthatdoesnotemergefromformalmedicalquestioning.Thisstepalsoimmediatelyconveysthatyouareinterestedinthepatientasapersonandnotjustasadisease.Generalconsiderations31Numerousspecialfeaturesofendocrinediseasemakepatientpresentationquitedifferentfromthatseeningeneralmedicine.Oneisthediscoveryofabnormalitythroughscreeningofasymptomaticindividuals,forexample:ahighserumcalciumleveldiscoveredthroughmultiphasicscreening;ahighbloodglucoseleveldiscoveredinashoppingmallkiosk.Theveryabsenceofsymptomslendsanunrealitytothemomentandshouldbecomeanexplicittopicofthepatient-doctorinteraction.Inthiscircumstance,itisworthemphasizingthevalueofearlydiscoveryandpreventionofgreatermorbidity.SPECIALFEATURESOFENDOCRINEILLNESS32Thesymptomsofendocrinedisordersoverlapagreatrangeofnormalcharacteristics,inclu