enrinology内分泌总论

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DisordersofendocrineandmetabolicsystemWangxinjun（王新军）DepartmentofendocrinologyHainanmedicalcollegeMP:18789826999 DefinitionsandscopeofendocrinologyClassicalendocrinology（经典内分泌学）isthestudyofendocrineglandswhichareagroupofglandsinthebodysecretinghormonestoevokeaspecificresponseinothercellsofthebody. ClassicalendocrineglandsPineal（松果体）Pituitary（垂体）Thyroid（甲状腺）Parathyroid（甲状旁腺）Adrenal（肾上腺）Islets（胰岛）gonads（性腺） Endocrineendo-crineendo-acombiningformmeaning“within,”usedintheformationofcompoundwords:endocardial;endocrinologycrine:paracrineautocrineexocrine EndocrinologyWithdevelopment,thedefinitionandscopeofinvestigativeandclinicalendocrinologycontinuestoexpand.Forexample:heart,kidney,adiposetissue ComponentsoftheendocrineandmetabolicsystemsArchitecturalandfunctionalpropertiesofendocrineandmetabolicsystem EndocrinesystemEndocrinesystemconsistsoftwomainparts:EndocrineglandsSporadicendocrinetissuesandcellsinnon-endocrineorgan Hypothalamus-pituitary-targetgland Hypothalamus-pituitary anteriorpituitaryreleasessixhormones:ACTH、TSH、FSH、LH、PRL、GHposteriorpituitaryreleasestwohormonesthatareactuallyproducedinthehypothalamus:antidiuretichormone(ADH)actsonthekidneystoconservewaterandalsopromotesconstrictionofbloodvessels.oxytocinstimulatesuterinecontractionsandpromotesmilk“letdown”inthebreastsduringlactation. HORMONETARGETFUNCTIONThyroid(TSH)StimulatingThyroidglandTHsynthesis&releaseGrowth(GH)ManytissuesgrowthAdrenocortico-Tropin(ACTH)AdrenalcortexCortisolrelease(androgens)Prolactin(Prl)BreastMilkproductionFollicle(FSH)GonadsEgg/spermprod.Luteinizing(LH)GonadsSexhormones Anexcessofgrowthhormoneinchildrencausesgiantism.Inadultsitcausesacromegaly.dwarfism(lackofgrowthhormone).ExcessACTHoverstimulatestheadrenalcortex,resultinginCushingdisease. Increasedprolactincausesmilksecretion,orgalactorrhea,inbothmalesandfemales.AspecificlackofADHfromtheposteriorpituitaryresultsindiabetesinsipidus(polyuriaandpolydipsia). HormonesPituitaryTSH，ACTH，GH，PRL，LH，FSHPeripheralglandThyroid：T3，T4Parathyroid：PTHAdrenal：cortisol、aldosteroneGonads：T，DHT，E，PLiver：IGFkidney：1，25(OH)2D3islets：insulin,glucagon（胰高血糖素） Apartfromtheseglands,therearemanytissuesandcellssparselydistributedinnon-endocrineorgans,suchastheatriumoftheheart,theliver,thekidney,thegastrointestinaltractandtheadiposetissues. ClassificationofhormoneHormonesarecustomarilydividedintothreegroups:Proteinsandpeptides:insulin（蛋白质和肽类激素）Steroids:cortisol（类固醇激素）Aminoacidanalogues:T3,T4（氨基酸类激素） SteroidsTissueswhichproducesteroidhormonesincludeovary/testis,adrenalcortex,placentaandskin(vitaminD).Allsteroidhormonesarebasedontheprecursormoleculecholesterol. RegulationofhormonelevelsSpontaneous,orbasal,hormonereleaseFeedbackinhibitionbyhormonesoftheirsynthesisand/orreleaseStimulationorinhibitionofhormonereleasebysubstancesthatmayormaynotberegulatedbythesamehormones EstablishmentofcircadianrhythmsforhormonereleasebysystemssuchasthebrainBrainmediatedstimulationorinhibitionofhormonereleaseinresponsetoanxietyanticipationofaspecificactivity,orothersensoryinputs. Hypothalamus-pituitary-adrenalaxisThehypothalamusproducesCRH,whichtravelsdowntheportalvesselsthroughthehypothalamicstalktotheanteriorpituitary,whereitstimulatesACTHrelease.ACTHthentravelstotheadrenalgland,whereitstimulatesthereleaseofcortisol. CortisolinturninhibitsbothCRHandACTHrelease（feedbackinhibition）.ThebrainestablishescircadianrhythmsandcantriggerincreasedCRHreleaseinresponsetostress. CRHACTHcortisol MechanismsofhormoneactionPeptideandcatecholaminehormonesandprostaglandinsbindtoreceptorsonthecellsurface.Steroidandthyroidhormonesactforthemostpartbybindingtointracellularreceptors. bindingtoreceptorsonthecellsurfacebindingtointracellularreceptors hormonesbindtoreceptorsonthecellsurfacePeptideandcatecholaminehormonesandprostaglandinsbindtoreceptorsonthecellsurface,wherethehormone-receptorinteractionsaffectintracellularmediators,orsecondmessengers. SecondmessengerscAMP:Glucagon,ACTH,PTHProteinkinaseactivityInsulinCalciumAlpha-adrenergicagonists,ATIIphospholipidsADH,GnRH,TRH. hormonesbindtoreceptorsonthecellsurface bindingtointracellularreceptors intracellularreceptors Disordersoftheendocrineandmetabolicsystem Mostrecognizabledisordersoftheendocrinesystemareduetoanexcessoradeficiencyofparticularhormones,whethercausedbyabnormalitiesofendocrineglands,ectopicproductionofhormones,abnormalconversionofprohormonestotheiractiveforms,oriatrogenicfactors. HypofunctionofendocrineglandsEndocrineglandsmaybeinjuredordestroyedbyneoplasia,infections,hemorrhage,autoimmunedisorders,andothercauses. HormonedeficiencysecondarytoextraglandulardisordersImpairedconversionofaprohormonetoahormoneoccursinchronicrenalfailure,inwhichthereisdefectiveconversionof25-hydroxycholecalciferolto1,25-dihydroxycholecalciferol. HyporesponsivenesstohormonesHormonelevelsmaybenormalorevenelevatedinthepresenceofmanifestationsofendocrinedeficiency. HormoneexesssyndromeHyperfunctionofendocrineglandsEctopichormoneproductionHormoneadministrationTissuehypersensitivity HyperfuctionofendocrineglandsThemostcommoncauseofhormoneexcesssyndromesishyperfunctionofendocrineglandssecondarytotumorsoftheglandsorhyperplasiaofseveralcauses. MetabolicdisordersDiabetesmellitusHypoglycemiaHyperuricemiaandgoutDisordersoflipidmetabolismNutritional/vitamindeficiencies SymptomsandsignsofendocrineandmetabolicdiseasesHormonesaffectthefunctionofalltissuesandorgansystems.Consequently,thesymptomsandsignsofendocrinediseaseareextremelydiverse.Theymayvaryfromgeneralized,suchasfatigue,tolocalized,suchasweaknessoftheextraocularmuscles. GeneralizedsymptomesWeaknessandfatigueMentalchangesUnintendedweightlossWeightgainAbnormalbodytemperature HypersecretionofAdrenalCortex SymptomesOphthalmicabnormalitiesAbnormalskinpigmentationHirsutismGynecomastiaGalactorrheaAbnormalappetiteDiarrhea SymptomesAnemiaTachycardiaandbradycardiaPolyuriaAmenorrheaoroligomenorrheaInfertilityBonepainandpathologicfracture HyposecretionofTH GH=pituitarydwarfism Physicalandlaboratoryexaminationanddiagnosis HistoryandphysicalexaminationManysyndromesofhormonalexcessordeficiencydisplaymanifestationsthatarereadilyapparentatthetimeofinitialpresentation,e.g.,severethyrotoxicosisandcushing’ssyndrome.Inotherinstances,theclinialpresentationismoresubtleandthephysicianmustrelyonlaboratorytestingtoestablishadiagnosis. LaboratorytestingTheleveloffreeratherthantotalhormoneisusuallythebestindexoftheeffectivehormoneconcentrationinplasma.Ameasurementofthe24-hurinefreecortisolusuallyprovidesareasonableestimateoftheintegratedlevelsoffreeplasmahormone. 正常人240008001600库欣病患者240008001600正常人和库欣患者的血F昼夜节律 ClinicalinterpretationThecliniciansmustrememberthatinbothmormalsubjectsandpatientswithendocrineandotherdiseases,hormonelevelsareextensivelyregulated.Forinstance,plasmainsulinlevelsshouldbeevaluatedinrelationtotheplasmaglucoseconcentration,andPTHlevelsshouldbeconsideredinrelationtoserumcalciumlevels. ClinicalinterpretationSincecortisolproductionintegratedovera24-hperiodisincreasedincushing’ssyndrome,the24-hurinaryfreecortisolprovidesamoreaccurateindexofcortisolhypersecretion. ClinicalinterpretationSometimesthesignificanceofhormonelevelscanbeevaluatedonlybythesimultaneousmeasurementofmorethanonehormone.Forinstance,withprogressivedamagetothethyroidhormones,secretionofTSHincreasesinacompensatoryfashionsothatnormalplasmalevelsofthethyroidhormonesmaybemaintained. GD的自身免疫发病机制 ClinicalinterpretationPlasmaestrogensarelowinovarianfailure.Ifovarialfailureisduetodiseaseoftheovary,plasmagonadotropinswillbeelevated.Ifovarianfailureissecondarytopituitaryorhypothalamicdisease,plasmagonadotropinlevelswillbenormalordecreased. DynamictestingProvocativetestingassessestheabilityofaglandtorespondtostimuliasanindexofitsreservecapacity.Insulininducedhypoglycemiaisusedtoassessthesecretoryabilityofcellsthatproducegrowthhormone. TeststhatprovideindirectinformationDiagnosisofdiabetesmellitusandassessmentoftherapydependonmeasurementofplasmaglucoseratherthaninsulinlevels.Itishelpfultofollowtheserumcalciumlevelsinhyperparathyroidismandtheserumpotassiumlevelsinprimaryaldosteronism. TeststhatprovideindirectinformationForinstance,serumsodiumisalmostalwaysgreaterthan139mEq/literinpatientswithanaldosteroneproducingadenoma,plasmacholesteroltendstobehighinhypothyroidismandlowinhyperthyroidism. TreatmentofendocrineandmetabolicdiseaseForendocrinedeficiencysyndromes,hormonesaregenerallyadministeredtocounterthedeficiency. VitaminDisgiveninsteadofPTHtotreathypoparathyroidism,sinceitcanincreasetheextracellularCa+. Incasesinwhichhormoneresistanceispresent,stepsaretakenwhenpossibletoalleviatethis,suchasthroughdietrestrictionintype2diabetes. Inhormone-excesssyndromes,avarietyofapproachesareused.Hyperfuctioningtumorsareremovedordestroyedwithradiotherapywhenpossible,andsometimeshyperplasticglandsareremoved. Inothercasesdrugsaregiventoblockhormoneproductionandrelease,suchasmethimazole/propylthiouracilforthyrotoxicosisandcabergoline/bromocriptineforprolactin-producingadenomas. Antagonistssuchasspironolactonecansometimesbeusefulinprimaryaldosteronismduetohyperplasia.