Normal pituitary response to metyrapone in the morning in depressed patients: Implications for circadian regulation of corticotropin-releasing hormone secretion

Excess secretion of cortisol in depressed patients has been documented by a number of investigators, which is presumed secondary to increased corticotropin (ACTH) and ACTHreleasing hormone (CRH) secretion. To unmask the proposed increased central (CRH) drive, we administered metyrapone in the AM to 13 depressed and 13 age- and sex-matched normal control subjects. Metyrapone administration resulted in a prompt decrease in plasma cortisol and in an increase in 11-deoxycortisol, the inactive precursor, in all subjects. Both depressed patients and normal control subjects demonstrated clear increases in ACTH and β-lipotropin/ β-endorphin production. There were no significant differences between patients and controls in any hormonal measures following metyrapone administration. These data suggest that: 1) in the absence of negative feedback (cortisol blockade), mildly to moderately depressed outpatients do not manifest increased central drive in the morning; and 2) the secretory capacity of the corticotropes do not differ between such depressed patients and controls.