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 increase d corticotropin (ACTH) and ACTH-releasing hormone (CRH) secretion. To unmask the proposed increased central (CRH) drive, we administered met yrapone in the AM to 13 depressed and 13 age- and sex-matched normal c ontrol subjects, Metyrapone administration resulted in a prompt decrea se in plasma cortisol and in an increase in 11-deoxycortisol, the inac tive precursor, in all subjects, Both depressed patients and normal co ntrol subjects demonstrated clear increases in ACTH and beta-lipotropi n/ beta-endorphin production. There were no significant differences be tween patients and controls in any hormonal measures following metyrap one administration. These data suggest that: I) in the absence of nega tive feedback (cortisol blockade), mildly to moderately depressed outp atients do not manifest increased central drive in the morning; and 2) the secretory capacity of the corticotropes do not differ between suc h depressed patients and controls. (C) 1997 Society of Biological Psyc hiatry.