Recovery from glucocorticoid inhibition of the responses to corticotrophin-releasing hormone.
We have characterized the recovery of the hypothalamic-pituitary-adrenal (HPA) axis from inhibition by short-term prednisolone administration. Prednisolone was given in a dosage averaging 25 mg at 12 h intervals orally for up to 2 weeks to adult volunteers. Human corticotrophin releasing hormone (hCRH) tests were performed at 0901 h using a bolus injection of 1 microgram/kg before and 24-48 h after discontinuing the prednisolone. In the initial control study, hCRH stimulated a two-fold rise in plasma ACTH and a 30% rise in plasma cortisol within 30 min (ACTH rose from 18.5 +/- 4.5, SEM, pg/ml to 36.5 +/- 12.6 pg/ml and cortisol from 415 +/- 58 to 531 +/- 69 nmol/l in response to hCRH. One dose of prednisolone had no effect on the ACTH or cortisol response to hCRH administered 24 h later. Twenty-four hours after discontinuing a 1 week course of prednisolone, baseline plasma ACTH (3.9 +/- 0.6 pg/ml) and cortisol (146 +/- 17 nmol/l) were markedly suppressed, as was the cortisol response to hCRH (peak 198 +/- 22). However, the plasma ACTH response to hCRH was not significantly suppressed. Forty-eight hours after discontinuing prednisolone, the recovery of ACTH secretion was complete (baseline 10.9 +/- 4.2, peak 36.4 +/- 14.8 pg/ml), but the cortisol response to hCRH was still depressed (peak 294 +/- 66 nmol/l). Recovery from a 2 week course of prednisolone had similar characteristics except plasma cortisol was depressed more profoundly. Plasma dehydroepiandrosterone (DHA) during hCRH tests and dehydroepiandrosterone sulphate (DHAS) paralleled plasma cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)
Watson
A C
AC
University of Chicago Pritzker School of Medicine, Departments of Pediatrics and Medicine, Illinois 60637.
Rosenfield
R L
RL
Fang
V S
VS
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D004334:Drug Administration Schedule; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*
D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D011239:Prednisolone; D006854:Hydrocortisone