title: ACTH response to corticotropin releasing hormone in Cushing's disease before and after ketoconazole: in vivo and in vitro studies.
abstract: Ketoconazole has been used as a palliative treatment of Cushing's syndrome, due to its ability to lower cortisol production. We evaluated the effects of ovine Corticotropin Releasing Hormone (oCRH) 100 micrograms i.v. on ACTH and cortisol levels in 6 patients with Cushing's disease before and after treatment with ketoconazole 600 mg/day. Both hormones increased after oCRH. During ketoconazole, cortisol was lowered to normal levels and its response to oCRH was impaired. After treatment, basal ACTH showed variable changes while the response to oCRH was markedly enhanced compared to that before ketoconazole. In vitro: In a continuous perfusion system of isolated anterior pituitary cells from rats or human anterior pituitary adenoma, producing ACTH, ketoconazole 10(-5)-10(-6) M showed no inhibitory effects on both basal or lisine-vasopressin and oCRH stimulated ACTH secretion. Our findings confirm the inhibitory action of ketoconazole on basal and stimulated cortisol secretion. No inhibition of ACTH levels was observed both in vivo and in vitro.
authors.affiliation: Institute of Semeiotica Medica, University of Padua, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Boscaro
authors.forename: N
authors.initials: N
authors.lastname: Sonino
authors.forename: A
authors.initials: A
authors.lastname: Rampazzo
authors.forename: A M
authors.initials: AM
authors.lastname: Menegus
authors.forename: F
authors.initials: F
authors.lastname: Mantero
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000818:Animals; D003346:Corticotropin-Releasing Hormone; D003480:Cushing Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007654:Ketoconazole / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D007654:Ketoconazole; D006854:Hydrocortisone