Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects

OBJECTIVE The standard ACTH test in clinical use employs a pharmacological dose of ACTH which assesses the maximum secretory capacity of the adrenal cortex. We have investigated the responses of plasma adrenocortical steroids including cortisol, aldosterone and dehydroepiandrosterone (DHEA) to physiological doses of ACTH (ACTH 1–24, tetracosactide, Cortrosyn) and determined the minimal dose which induces a response equivalent to that induced by a pharmacological dose of ACTH. DESIGN Rapid ACTH tests at various physiological (0.1, 0.5, 1 and 5μg) and standard pharmacological (250μg) intravenous doses. SUBJECTS Seven healthy normal volunteers. MEASUREMENTS Plasma cortisol, aldosterone and DHEA were measured. Peak value and the increment from basal value were used as indices of responses. RESULTS Each steroid responded to physiological doses of ACTH in a dose dependent manner. The minimum dose inducing an equivalent response to 250μg ACTH was 0.5μg for peak and incremental values in cortisol and DHEA, while that for aldosterone was 0.1μg. The time to peak for each steroid was delayed as the dose increased. Plasma aldosterone and DHEA peaked significantly earlier than plasma cortisol in 1–5μg and 0.5–5-μg ACTH tests, respectively. CONCLUSIONS These results suggest that the sensitivity of secretion to physiological doses of ACTH in descending order is aldosterone > DHEA = cortisol. When peak and incremental values are used, sufficient doses of ACTH are 0.1μg for plasma aldosterone and 0.5μg for plasma cortisol and DHEA in the rapid ACTH test.