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Cortisol Response in Relation to the Severity of Stress and Illness

Division of Endocrinology, Diabetes, and Clinical Nutrition (I.E.W., J.J.P., C.K., J.G., B.M.), Division of Operative Critical Care (H.P.), and Clinic of Cardio-Thoracic Surgery (H.R.Z.), University Hospital, CH-4031 Basel, Switzerland

Address all correspondence and requests for reprints to: Dr. Jardena J. Puder, Clinic of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital, CH-4031 Basel, Switzerland. E-mail: puderj{at}uhbs.ch.

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 µg 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-µg 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 µg compared with 1 µg 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 µg compared with 1 µg ACTH. Data from our study give insight into the physiological adaptations of the hypothalamic-pituitary-adrenal axis to stress.

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