Plasma Steroid Profiles in Subclinical Compared With Overt Adrenal Cushing Syndrome

CONTEXT: Diagnosis of subclinical adrenal hypercortisolism is based on several tests of the hypothalamic-pituitary-adrenal axis to establish mild alterations of cortisol secretion and dysregulated cortisol physiology. OBJECTIVE: We assessed whether plasma steroid profiles might assist diagnosis of subclinical Cushing syndrome (SC). DESIGN: Retrospective cross-sectional study. SETTING: Two tertiary medical centers. PATIENTS: Of 208 patients tested for hypercortisolism, disease was excluded in 152 and confirmed in 21 with overt adrenal Cushing syndrome (AC) compared to 35 with SC. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for reference. MAIN OUTCOME MEASURES: A panel of 15 plasma steroids was measured by mass spectrometry, with classification by discriminant analysis. RESULTS: Patients with SC had lower plasma concentrations of dehydroepiandrosterone and dehydroepiandrosterone-sulfate than subjects without SC (P < 0.05). The largest increases (P < 0.001) in plasma steroids among patients with SC were observed for 11-deoxycortisol and 11-deoxycorticosterone. Nevertheless, concentrations of 11-deoxycorticosterone, 11-deoxycortisol, and pregnenolone in patients with AC were higher (P < 0.05) than in those with SC. Patients with SC or AC could be distinguished from subjects without disease using this combination of steroids as precisely as with use of measurements of serum cortisol after administration of dexamethasone. The steroid combination provided superior diagnostic performance compared with each of the other routine biochemical tests. CONCLUSION: Distinct plasma steroid profiles in patients with SC may provide a simple and reliable screening method for establishing the diagnosis.