Objective To estimate the dose dependence of endogenous ACTH stimulation of adrenal cortisol secretion overnight. Design 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). Subjects Healthy adults. Measurements ACTH dose-responsive estimates. Results 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 50s 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. Conclusions 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.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism