Crofford, Leslie J, Young, Elizabeth A, Engleberg, N Cary et al. · Brain, behavior, and immunity · 2004 · DOI
This study measured stress hormones (ACTH and cortisol) throughout a 24-hour period in patients with fibromyalgia, chronic fatigue syndrome, or both, compared to healthy controls. Researchers found that fibromyalgia patients had abnormal cortisol patterns—particularly elevated levels in the evening and delayed decline throughout the day—suggesting their stress hormone system doesn't recover properly. Chronic fatigue syndrome patients showed some differences but they were smaller and not statistically significant.
HPA axis dysfunction is a proposed biological mechanism in both ME/CFS and fibromyalgia. This study provides objective evidence of abnormal stress hormone patterns, particularly in fibromyalgia, which could help explain fatigue, pain, and immune dysregulation. Understanding whether HPA axis changes are disease-causing or secondary could inform future treatments targeting the stress response system.
This study does not establish causation—abnormal cortisol patterns could be a consequence of chronic illness rather than a cause. The findings in CFS patients were not statistically significant, so no firm conclusions about HPA axis dysfunction in CFS alone can be drawn from this data. The study excluded patients with psychiatric disorders, so findings may not apply to patients with comorbid depression or anxiety.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Crofford, Leslie J, Young, Elizabeth A, Engleberg, N Cary, Korszun, Ania, Brucksch, Christine B, McClure, Leslie A, et al. (2004). Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome.. Brain, behavior, and immunity. https://doi.org/10.1016/j.bbi.2003.12.011
BibTeX
@article{mecfsatlas-crofford-2004-basal-circadian,
author = {Crofford, Leslie J and Young, Elizabeth A and Engleberg, N Cary and Korszun, Ania and Brucksch, Christine B and McClure, Leslie A and Brown, Morton B and Demitrack, Mark A},
title = {Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome.},
journal = {Brain, behavior, and immunity},
year = {2004},
doi = {10.1016/j.bbi.2003.12.011},
note = {PubMed: 15157948},
url = {https://www.mecfsatlas.com/evidence/crofford-2004-basal-circadian},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/crofford-2004-basal-circadian
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