Cushings syndromeHormonesReceptors-hormone action“To set in motion”The classification of endocrine disorders Excess of hormone Administration of exogenous hormone or medication Deficiency of hormone Resistance to hormoneHormonesReceptors-hormone actionCushings syndromeChronic glucocorticoid excess, whatever its cause, leads to the constellation of symptoms and physical features.GlucocorticoidreceptorCascadeeffectACTHCRHPeripheral glands- adrenal cortex hypothalamuspituitaryTarget cellTarget cellCortisol binding proteinGlucocorticoidACTHCRHadrenal cortex hypothalamuspituitaryCauses of glucocorticoid excessACTH dependent Cushings syndromeACTH independent Cushings syndromePituitary adenoma-Cushings diseasenonPituitary neoplasm-ectopic ACTHunilateral adrenal neoplasm-adenoma,carcinomaBilateral nodular adrenal hyperplasia-small nodular-large nodularClinical features of Cushings syndrome Common symptoms and signs Features suggesting a specific causeClinical features of Cushings syndrome Common symptoms and signsCaused by chronic glucocorticoid excess Features suggesting a specific causestriaePsychologic disturbanceMucocutaneous fungal infectionGonadal dysfunctionMetabolic disorderCommon symptoms and signsCentral obesityplethoraEasy bruisingFine cigarette paper thin” skinosteoporosisClinical features of Cushings syndrome Common symptoms and signs Features suggesting a specific causeGlucocorticoidACTHCRHadrenal cortex hypothalamuspituitaryACTH dependent Cushings syndromeACTH independent Cushings syndromePituitary adenoma-Cushings diseaseDepending on the size of adenomaFemale predominance, slow progressionnonpituitary neoplasm-ectopic ACTHMale predominanceQuick progression,adrenal neoplasm-adenoma,-carcinomarapid onset, progression,Bilateral nodular adrenal hyperplasia-small nodular-large nodularFeatures suggesting a specific causeFeatures of corticol excess onlyFeatures of androgens and aldosterone excess DiagnosisHistory & physical examinationLaboratory studiesFunction diagnosisPathology diagnosisEtiology adiagnosisFunctional evaluation: Basal level Stimulation test Inhibitory test Plasma vs. Urine Total vs. Free TimeGlucocorticoidACTHCNS inputCRHadrenal cortexhypothalamuspituitaryTarget cellspontaneous rhythms Diurnal rhythmsDisappear(8AM,4PM,12MN)24hr UFCBasal levelFunctional evaluation: Basal level24h Urine17-OHSCFree cortisol Plasma: Diurnal rhythms of cortisolGlucocorticoidACTHCNS inputCRHadrenal cortexhypothalamuspituitaryTarget cellInhibitory testLow dose Dex testlarge dose Dex testStimulation testInhibitory testStimulation testCRH stimulation testFunctional evaluation: Stimulation testCRH stimulation test Inhibitory test Low dose Dex test large dose Dex testDiagnosisFunction diagnosisPathology diagnosis-Biopsy proceduresEtiology diagnosis-Imaging studiesCushings syndrome establishedACTH-IRMA10pg/mlCT adrenalsMRI pituitaryUnilateral massBilateral enlargementAdrenal surgeryEctopic ACTHPituitary surgeryPeak ACTH20pg/mlNormalabnormalCRH test +IPSSIPS:P2.0CRH test10pg/ml？AdenomacarcinomaAIMAHPPNADBilateral adenomaGlucocorticoid excessACTHCRHadrenal cortex hypothalamuspituitaryTreatment: DrugSurgeryRadiationRemoveblock synthesisDrugSurgeryRemoveblock synthesisDrugblock actionTreatment choice depending on the cause of CS.CabergolineSSA: Pasireotidemifepristoneketoconazole metyrapone mitotaneGlucocorticoidACTHCRHadrenal cortex hypothalamuspituitaryACTH dependent Cushings syndromeACTH independent Cushings syndromePituitary adenoma-Cushings diseasenonpituitary neoplasm-ectopic ACTHadrenal neoplasm-adenoma,-carcinomaBilateral nodular adrenal hyperplasia-small nodular-large nodularketoconazole mitotaneketoconazole etomidateketoconazoleketoconazole etomidateketoconazole mitotane mitotane mitotanemetyrapone mitotaneetomidate metyrapone mitotaneetomidate mitotaneHormone replacement1 Hyperpigmentation2 ACTH3 Pituitary adenomaNelson syndromeKey CS factors Theres no hormone test that is superior to clinical judgment Treat the patient, not the lab。
