Cortisol response in relation to the severity of stress and illness

J Clin Endocrinol Metab. 2005 Aug;90(8):4579-86. doi: 10.1210/jc.2005-0354. Epub 2005 May 10.


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 microg 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-microg 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 microg compared with 1 microg 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 < or = 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 microg compared with 1 mug ACTH. Data from our study give insight into the physiological adaptations of the hypothalamic-pituitary-adrenal axis to stress.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Adrenocorticotropic Hormone* / administration & dosage
  • Adrenocorticotropic Hormone* / blood
  • Adult
  • Aged
  • Coronary Artery Bypass
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / surgery
  • Diagnostic Techniques, Endocrine / standards
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Hypothalamo-Hypophyseal System / physiology
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiology
  • Reproducibility of Results
  • Severity of Illness Index*
  • Stress, Physiological / blood*
  • Stress, Physiological / diagnosis


  • Adrenocorticotropic Hormone
  • Hydrocortisone