皮質(zhì)醇增多癥的診治課件

Hypercortisolism

(Cushing’sSyndrome)

DefinitionAconstellationofclinicalabnormalitiesduetochronicexposuretoexcessofcortisolorrelatedcorticosteroid.ItisraredisorderItoccursasaresultofprimarytumorsofadrenalglandthathypersecretecortisolexcessACTHsecretionthatmaybeofpituitaryornonpituitarysourcesNormalpatternofACTHandcortisolsecretionPulsatilesecretionCircadianrhythmWhenstimulatedbyACTH,theadrenalglandsecretescortisolandothersteroidhormones.ACTHisproducedbythepituitaryglandandreleasedintothepetrosalvenoussinusesinresponsetostimulationbycorticotropin-releasinghormone(CRH)fromthehypothalamusEtiologyandPathophysiologyTABLE204-2.CAUSESOFCUSHING’SSYNDROMEACTH-dependentcausesACTH-secretingpituitarytumor(Cushing’sdisease)PituitaryACTH-secretingneoplasm(ectopicCRHsyndrome)NonpituitaryACTH-secretingneoplasm(ectopicACTHsyndrome)ACTH-independentcauses

AdrenaladenomaAdrenalcarcinomaMicronodularadrenaldiseaseMcCune-AlbrightsyndromeMassivemacronodularadrenaldiseasePseudo-CushingSyndrome

FactitiousorsurreptitiousglucocorticoidadministrationNormalAppearanceWithCushingsWithCushingsNormalAppearanceFIGURE.MultiplewidestriaeontheabdomenofapatientwithCushing'sdisease.TABLE204-1.CLINICALFEATURESOFGLUCOCORTICOIDEXCESS

Frequency(%)Weightgain 90“Moonfacies” 75Hypertension 75Violaceousstriae

65Hirsutism 65Glucoseintolerance 65Proximalmuscleweakness 60Plethora 60Menstrualdysfunction 60Acne 40Easybruising 40Osteopenia 40Dependentedema 40Hyperpigmentation 20Hypokalemicmetabolicalkalosis 15DiagnosisClinicalmanifestationsLabfindingsPlasmacortisolandrhythm(RIA)Urinaryfreecortisol17-hydroxycortisteriod(17-羥皮質(zhì)類固醇)17-ketosteriods(17-酮皮質(zhì)類固醇)PlasmaACTHScreeningTestsforCushing’sCourtesyofwww.CSRF.comSuppressiontestsScreeningtest1mgDXP.OatmidnightPlasmacortisol(PF)at7-8amnextdayPFsuppressed:NormalPFNOTsuppressed:Cushing’sSyndromeSuppressiontestsLargedoseDXsuppressiontestD.X2mgq6hP.O2daysUrinaryfreecortisolreduced50%:Cushing’sdisease(Pituitaryadenoma)UrinaryfreecortisolNOTreduced50%:Adrenaltumor,carcinoma,ectopicACTHSyndromeACTHStimulationtestACTH25uintravenously8h2-5foldincreaseinurinaryfreecortisolinCushing’sdiseasePlasmacortisolandurinaryfreecortisolincreaseinhalfofadrenaladenomapatientsNoresponseinadrenalcarcinomaMetyraponeTestEtiologydiagnose(especiallyforpituitaryoradrenal)Metyrapone2-3g(30mg/kg)P.OatmidnightUrinary17-OHCS,PlasmaACTH,11-deoxycortisolmoreabovebasallevel:Cushing’sdisease(Pituitaryadenoma)Noresponseinadrenalcarcinoma,tumor,ectopicACTHSyndromeImagingdiagnosisPituitaryCThasasensitivityofabout50%foridentifyingmicroadenomasMRI

hasincreasedsensitivitybutisnot100%predictiveIfdiagnosticdoubtneedbilateralinferior

petrosalsinussamplingforACTHAdrenalultrasonography---firstchoiceAbdominalCTwillallowidentificationofadrenalpathologySomatostatinscintigraphytoidentifysitesofectopichormoneproductionEtiologicaldiagnosisCushing’sdisease: Adrenaladenoma: Adrenalcarcinoma: EctopicACTHSyndrome: Chronic,moderateclinicalfeaturescanbe

suppressedbylargedosetestShortercourse,mildfeaturescanNOTbesuppressedbylargedosetestAcuteonset,progressivecourse,hyperandrogeniceffectpredominate,palpablemass,lowACTHAppearsuddenly,progressrapidly,nottypicalmanifestationofCushing’ssyndrome,hyperpigmentation,hypokalemia,highACTHDifferentialdiagnosisSimpleobesityGeneralobesity,longhistory,overnourishedNarrowandshortstriaeUrinaryfreecortisolcanbesuppressedbyscreening(overnight)testand/orlow-doseDXsuppressiontestNormaldiurnalrhythm,almostnormalplasmacortisolType2DMNormalplasmacortisolandrhythmOncebloodglucosecontrolled,urinaryfreecortisolturnstonormalAlcoholicCushingnoidSyndromeNodrinkingforoneweek,plasmacortisolandurinaryfreecortisolbecomenormalDepressionLackofclinicalmanifestationofCushing’sSyndromeTreatmentCushing’sdiseaseTranssphenoidalmicroadenomectomyPituitaryradiationBilateraltotaladrenolectomyDrugsAdrenaladenomaandcarcinomaSurgicalremovalDrugs(mitotane,metyrapone,ketoconazole)fornonresectableormetastaticcarcinomaEctopicACTHSyndromeSurgicalremovaloftheectopictumorChemotherapy,radiotherapyDrugs(mitotane,metyrapone,ketoconazloe)MedicaltherapyofCushing’sDisease

PurposeCorrectmetabolicabnormalitiesbeforeattemptedsurgicalcurePalliatesurgicallynoncurablediseaseAchieveremissioninpatientsforwhomsurgeryisunlikelytoachievesatisfactorylongtermresultsSteroidogenicinhibitionMitotane(OP’-DDD,雙氯苯三氯乙烷)Metyrapone(Su4885,美替拉酮)Aminoglutethimide(氨基導(dǎo)眠能)Ketoconazole(酮康唑)NeuromodulatorytreatmentBromocriptine(