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Attenuated morning salivary cortisol concentrations in a population-based sample of cases with chronic fatigue syndrome and well controls.

Nater UM, Maloney E, Boneva RS, Jones JF, Reeves WC, Heim C.
Journal of Clinical Endocrinology & Metabolism 26 December 2007 doi:10.1210/jc.2007-1747.
First published ahead of print December 26, 2007

Summary

The pathophysiology of CFS clearly involves abnormal response to physical and mental stress and research increasingly indicates that hypothalamic pituitary adrenal (HPA) axis dysregulation is involved. Among other things, HPA axis response to stress involves cortisol secretion and results from several studies are consistent with HPA axis hypoactivity in persons with CFS. We conducted this study to compare normal daily HPA axis activity in persons with CFS identified from metropolitan, urban, and rural populations of Georgia. Salivary cortisol reflects HPA axis activity. In general, awakening is the first major stressor in an individual's day and salivary cortisol rapidly peaks within the first hour of awakening and then slowly declines throughout the day. We found that persons with CFS have significantly attenuated awakening salivary cortisol responses compared to healthy controls; these changes could be related to CFS symptoms, as some of our findings indicate, but no statement on a causal relationship can be made at this point. We were surprised that this attenuated awakening response was limited to women and were not observed in men with CFS, and this may in part explain the higher prevalence of CFS in women.

Abstract

Context: A substantial body of research on the pathophysiology of chronic fatigue syndrome (CFS) has focused on hypothalamic-pituitary-adrenal (HPA) axis dysregulation. The cortisol awakening response has received particular attention as a marker of HPA axis dysregulation.

Objective: The objective of the current study was to evaluate morning salivary cortisol profiles in persons with CFS and well controls identified from the general population.

Design: Case-control study.

Setting: This study was conducted at an outpatient research clinic.

Cases and Other Participants: We screened a sample of 19,381 residents of Georgia and identified those with CFS and a matched sample of well controls. Seventy-five medication-free CFS cases and 110 medication-free well controls provided complete sets of saliva samples.

Main Outcome Measures: Free cortisol concentrations in saliva collected on a regular workday, immediately upon awakening, 30 minutes and 60 minutes after awakening.

Results: There was a significant interaction effect, indicating different profiles of cortisol concentrations over time between groups, with the CFS group showing an attenuated morning cortisol profile. Notably, we observed a sex difference in this effect. Women with CFS exhibited significantly attenuated morning cortisol profiles compared with well women. In contrast, cortisol profiles were similar in men with CFS and male controls.

Conclusion: CFS was associated with an attenuated morning cortisol response but the effect was limited to women. Our results suggest that a sex difference in hypocortisolism may contribute to increased risk of CFS in women.

Page last modified on March 4, 2008

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