ONE MICROGRAM IS THE LOWEST ACTH DOSE TO CAUSE A MAXIMAL CORTISOL RESPONSE - THERE IS NO DIURNAL-VARIATION OF CORTISOL RESPONSE TO SUBMAXIMAL ACTH STIMULATION

There are many suggestions in the literature that the adrenal gland is moro sensitive to ACTH in the evening than in the morning. However, a ll these studies in humans were conducted when the basal cortisol leve l was not suppressed, and were based on the observation that, after st imulation, the increases in cortisol differed, though the peak values were the same, To examine this, we established the lowest ACTH dose th at caused a maximal cortisol stimulation even when the basal cortisol was suppressed and used a smaller dose of ACTH for morning and evening stimulation. The lowest ACTH dose to achieve maximal stimulation was found to be 1.0 mu g, with which dose cortisol concentration increased to 607.2 +/- 182 nmol/l, compared with 612.7 +/- 140.8 nmol/l with th e 250 mu g test (P > 0.3). The use of smaller doses of ACTH (0.8 and 0 .6 mu g) achieved significantly lower cortisol responses (312 +/- 179. 4 and 323 +/- 157.3 nmol/l respectively; both P < 0.01 compared with t he 1 mu g test). When a submaximal ACTH dose (0.6 mu g) was used to st imulate the adrenal at 0800 and 1600 h. after pretreatment with dexame thasone, no difference in response was noted at either 15 min 1372.6 /- 116 compared with 394.7 +/- 129.7 nmol/l) or 30 min (397.4 +/- 176. 6 compared with 403 +/- 226.3 nmol/l, P > 0.3 for both times). These r esults show that 1.0 mu g ACTH, used latterly as a low-dose test, is v ery potent in stimulating the adrenal, even when baseline cortisol is suppressed; smaller doses cause reduction of this potency. Our data sh ow that there is probably no diurnal variation in the response of the adrenal to ACTH, if one eliminates the influence of the basal cortisol level and uses physiologic rather than superphysiologic stimuli.