Plasma steroid profiles in subclinical compared to overt adrenal Cushing's 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 This study assessed whether plasma steroid profiles might assist diagnosis of subclinical Cushing's syndrome (SC). DESIGN Retrospective cross-sectional study. SETTING Two tertiary medical centers. PATIENTS Two hundred and eight patients were tested for hypercortisolism among whom disease was excluded in 152 and confirmed in 21 with overt clinical Cushing's syndrome due to adrenal tumors (AC) compared to 35 with SC. Another 277 age- and gender-matched hypertensive and normotensive volunteers were included for reference. MAIN OUTCOME MEASURES Panel of 15 plasma steroids measured by mass spectrometry with classification by discriminant analysis. RESULTS Patients with SC showed lower (P<0.05) plasma concentrations of dehydroepiandrosterone and dehydroepiandrosterone-sulfate than subjects without SC. 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 the above combination of steroids as precisely as with use of measurements of serum cortisol after dexamethasone. The steroid combination provided superior diagnostic performance compared to each of the other routine biochemical tests. CONCLUSIONS Distinct plasma steroid profiles in patients with SC may provide a simple and reliable screening method for establishing the diagnosis.