Inhibition of the pituitary-adrenal axis with dexamethasone and cortisol in depressed patients and healthy subjects: a dose-response study.
Different doses dexamethasone (0.25, 0.5, and 1 mg) or cortisol (30, 60, and 120 mg) were administered PO at 2230h to 39 depressed patients and 20 healthy subjects on nonsuccessive days. The inhibiting capacity of the two steroids on hypothalamo-pituitary axis (HPA) function was evaluated by measuring the plasma levels of cortisol, ACTH, and beta-endorphin at 0900h and 1530h each day following treatment. Baseline levels of the hormones were measured before starting treatment. A dose-dependent suppressive effect of both steroids on the plasma levels of cortisol, ACTH, and beta-endorphin was found both in patients and controls, except for the 0900h levels of cortisol after cortisol treatment. The effects were most profound in the morning. Differences between patients and controls were observed after cortisol treatment, but not dexamethasone, with respect to cortisol, ACTH, and beta-endorphin plasma levels in the morning. Cortisol treatment discriminated dexamethasone nonsuppressors from suppressors (patients and controls) and patients categorized as dexamethasone suppressors from controls in a way that dexamethasone treatment could not. The data favour the idea of impaired corticosteroid feedback beyond the pituitary level as part of HPA dysfunction.
Department of Psychiatry, Academic Hospital, Utrecht, The Netherlands.
C C
CC
Gispen-de Wied
H
H
D'Haenen
W M
WM
Verhoeven
H J
HJ
Wynne
H G
HG
Westenberg
J H
JH
Thijssen
J M
JM
Van Ree
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology; D003866:Depressive Disorder / Q000097:blood / Q000175:diagnosis* / Q000523:psychology; D003907:Dexamethasone; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D012016:Reference Values; D001615:beta-Endorphin / Q000097:blood
D001615:beta-Endorphin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone