OBJECTIVE The standard ACTH test in clinical use employs a pharmacolog
ical dose of ACTH which assesses the maximum secretory capacity of the
adrenal cortex. We have investigated the responses of plasma adrenoco
rtical steroids including cortisol, aldosterone and dehydroepiandroste
rone (DHEA) to physiological doses of ACTH (ACTH 1-24, tetracosactide,
Cortrosyn) and determined the minimal dose which induces a response e
quivalent to that induced by a pharmacological dose of ACTH. DESIGN Ra
pid ACTH tests at various physiological (0.1, 0.5 , 1 and 5 mu g) and
standard pharmacological (250 mu g) intravenous doses. SUBJECTS Seven
healthy normal volunteers. MEASUREMENTS Plasma cortisol, aldosterone a
nd DHEA were measured. Peak value and the increment from basal value w
ere used as indices of responses. RESULTS Each steroid responded to ph
ysiological doses of ACTH in a dose dependent manner. The minimum dose
inducing an equivalent response to 250 mu g ACTH was 0.5 mu g for pea
k and incremental values in cortisol and DHEA, while that for aldoster
one was 0.1 mu g The time to peak for each steroid was delayed as the
dose increased. Plasma aldosterone and DHEA peaked significantly earli
er than plasma cortisol in 1-5 mu g and 0.5-5 mu g ACTH tests, respect
ively. CONCLUSIONS These results suggest that the sensitivity of secre
tion to physiological doses of ACTH in descending order is aldosterone
> DHEA=cortisol. When peak and incremental values are used, sufficien
t doses of ACTH are 0.1 mu g for plasma aldosterone and 0.5 mu g for p
lasma cortisol and DHEA in the rapid ACTH test.