REPRODUCIBILITY OF THE CORTISOL RESPONSE TO STIMULATION WITH A LOW-DOSE OF ACTH(1-24) - THE EFFECT OF BASAL CORTISOL-LEVELS AND COMPARISON OF LOW-DOSE WITH HIGH-DOSE SECRETORY DYNAMICS

We compared the reproducibility and repeatability of the acute adrenal response to low doses (90 and 500 ng/ 1-73 m2) of Synacthen (ACTH(1-24)) with that of the standard dose (250 mug/1.73 m2). We also examined the effect of basal cortisol levels on peak values achieved after stimulation with a low dose. ACTH (1-24) was given to six male volunteers: 90 ng/1.73 m2 twice at 90-min intervals on day 1, and 90 and 500 ng/1.73 m2 once on day 2 and 250 mug/1.73 m2 once on day 3. The rise in serum cortisol concentration with repeated low doses of ACTH was not attenuated (161 +/- 49 (S.D.) nmol/l on initial vs 150 +/- 41 nmol//l on repeat stimulation; P=0.5) and this was reproducible (161 +/- 49 nmol/l on day 1 vs 148 +/- 15 nmol/l on day 2; P=0.6). A dose of 500 ng ACTH(1-24)/1.73 m2 produced a maximal adrenal response in that the rise in serum cortisol concentration at 20 min was identical with that produced at the same time by the standard dose of 250 mug/1.73 m2. There was a strong positive correlation between the basal cortisol level and peak cortisol concentration after low-dose ACTH stimulation (r=0.93, P<0.001) but not between the basal cortisol level and the incremental rise (r=-0.1, P=0.69). These results suggest that the cortisol response to low-dose ACTH stimulation is reproducible and not attenuated by repeat stimulation at 90-min intervals. The incremental rise in serum cortisol concentration after ACTH stimulation appears constant in these situations and is not influenced by the basal cortisol level. When there is concern that the standard dose may be excessive and mask subtle but important changes in adrenal function, the low dose (500 ng) of ACTH should be used.