Cortisol response in relation to the severity of stress and illness

Background: The aim of the study was to compare the adrenal response, the course of the ACTH/cortisol ratio, as well as the variance and the diagnostic performance of different cutoffs after 1 and 250 mu g ACTH stimulation in different stress situations. Methods: We investigated three groups with increasing stress levels: ambulatory controls ( group A; n = 20), hospitalized medical patients ( group B; n = 25), and patients undergoing coronary artery bypass grafting ( group C; n = 29). All subjects underwent four consecutive ACTH stimulation tests and were randomized to either a 1- or 250-mu g dose. Results: Stimulated cortisol levels in group A were similar to basal cortisol levels under maximal stress (C3; P = 0.8). Peak cortisol concentrations were higher after 250 mu g compared with 1 mu g ACTH in group B (P = 0.006) and under maximal stress after extubation ( group C3; P = 0.027), whereas there were no differences in group A. The ACTH/cortisol ratio was lower in surgical patients after extubation compared with unstressed conditions (P <= 0.03) The within-subject variance was similar in ambulatory controls and medical patients and after both ACTH doses (all 17-36% of total variance). Cutoff dependent, the diagnosis of relative adrenal insufficiency would have been made in 0-58.3%, respectively. Conclusion: In moderate and major stress situations, cortisol concentrations in patients without hypothalamic-pituitary-adrenal disease were higher after stimulation with 250 mu g compared with 1 mu g ACTH. Data from our study give insight into the physiological adaptations of the hypothalamic-pituitary-adrenal axis to stress.