Overnight ACTH-cortisol dose responsiveness: comparison with 24-h data, metyrapone administration and insulin-tolerance test in healthy adults

Abstract

To estimate the dose dependence of endogenous ACTH stimulation of adrenal cortisol secretion overnight. Ten-minute sampling for ACTH and cortisol over 8 and 24 h (n = 17), after metyrapone administration (n = 6), during an insulin-tolerance test (n = 7). Healthy adults. ACTH dose-responsive estimates. Twenty-four hour ACTH-cortisol concentration pairs yielded an estimated EC(50) (one-half maximally stimulatory ACTH concentration) of 5·1 (2·2-9·5) pmol/l [median (range)]. This did not differ from EC(50) s based on 8- or 6-h data [5·9 (3·5-11) and 7·5 (3·7-41) pmol/l] in the same individuals. ACTH efficacy (maximally stimulatable cortisol secretion rate) was 8·4 (3·1-20), 11 (5·9-24) and 15 (5·9-22) nmol/l/min, when calculated over 24, 8 and 6 h, respectively (P = NS). Adrenal sensitivity (slope term) was also consistent across sampling durations, viz. 14 (1·3-95), 18 (1·3-64) and 20 (1·3-64) slope units. Compared with placebo, metyrapone reduced ACTH efficacy from 11 (6·2-62) to 2·8 (1·5-4·5) nmol/l/min for cortisol (n = 9, P < 0·001), while increasing ACTH efficacy for 11-desoxycortisol from 2·3 (0·9-2·9) to 99 (70-218) nmol/l/min (n = 6, P < 0·01), thus affirming face validity. Combined ACTH and cortisol responses to hypoglycaemia allowed an estimate of ACTH efficacy of 28 (22-81) nmol/l/min, compared with the control value of 8·7 (5·6-26), suggesting enhanced adrenal responsiveness. The results suggest that endogenous ACTH-adrenal drive can be approximated from overnight 8-h sampling of paired ACTH and cortisol concentrations. This strategy may have merit in clinical research in childhood, pregnancy, anxiety states and frail elderly individuals, when ACTH injections are not desired.