Comparison of the cortisol responses to testing with two doses of ACTH in patients with suspected adrenal insufficiency

Objectives: To compare the cortisol response of the 1 mu g and the 250 mu g ACTH test in a large study of patients with suspected adrenal insufficiency. Design: Retrospective cohort study. Methods: Single center study assessing patients tested for primary or secondary adrenal insufficiency between January 2004 and December 2007, who had both ACTH tests (1 mu g and 250 mu g; n = 207) within a time interval of 6 weeks. Test results were compared with a Bland-Altman plot and McNemar's test. Results: The mean difference between the cortisol responses in the two ACTH tests was 26 nmol/l (95% confidence interval (CI) 13, 40), showing a marginally higher response for the 250 mu g test. The diagnostic performances of the two tests were similar (P = 0.49) using a cut-off value for cortisol of 550 nmol/l. A normal cortisol response to the 1 mu g ACTH test could be accompanied by an abnormal response to the 250 mu g ACTH test, and vice versa. Conclusion: This study shows that the 1 mu g and the 250 mg ACTH tests have comparable cortisol responses in patients with suspected adrenal insufficiency. However, in individual patients, the difference in cortisol response to the two tests can be substantial, and the response in the 250 mu g test is not invariably higher than the response in a 1 mu g test