Background & objectives: Cortisol response to 250 micrograms adrenocorticotropin (ACTH) exhibits no circadian variation. Information on the circadian variation, if any, in cortisol response to 1 microgram ACTH, which is considered as a physiological dose is not available. As the 1 microgram ACTH stimulation test is projected as an outpatients procedure with no time constraint, this information is very important. Hence, this study was designed to assess whether any circadian variability exists in cortisol response to 1 microgram ACTH in healthy subjects.
Methods: Thirty six healthy volunteers (23 male and 13 female) with mean age of 32.2 +/- 9.0 yr were consecutively studied after obtaining informed consent. On day 1, prestimulated and stimulated plasma cortisol samples were collected at 0800 h and, at 30 and 60 min following an intravenous bolus of 1 microgram ACTH, and on day 3, plasma cortisol samples were similarly collected at 1600 h. Cortisol estimation was done by a sensitive and specific radioimmunoassay. Stimulated plasma cortisol of 500 nmol/1 or more was defined as a normal response.
Results: The prestimulated and peak cortisol levels at 0800 h (377.5 +/- 93.3 and 729.1 +/- 183.2 nmol/l) were higher (P < 0.001 and P < 0.01) than those at 1600 h (230.1 +/- 75.7 and 665.8 +/- 138.6 nmol/l). However, a stimulated cortisol response of 500 nmol/l or more was observed at both 0800 h and 1600 h in all subjects at 30 min but not at 60 min. The [symbol: see text] (peak-basal) response was higher at 1600 h than that at 0800 h (432.8 +/- 136.8 vs 351.5 +/- 177.3, P < 0.01).
Interpretation & conclusion: The demonstration of normal cortisol response to 1 microgram ACTH both at 0800 h and 1600 h suggests that the test can be performed at any time of the day.