Demitrack, M A, Dale, J K, Straus, S E et al. · The Journal of clinical endocrinology and metabolism · 1991 · DOI
This study examined whether ME/CFS patients have a problem with their body's stress hormone system, specifically the network that controls cortisol production. Researchers found that ME/CFS patients had lower cortisol levels than healthy people, but their bodies were responding unusually to stimulation—suggesting the problem lies in the brain's control center rather than the adrenal glands themselves.
This foundational study provided early evidence that ME/CFS involves objective biological abnormalities in the HPA axis—a critical regulatory system governing stress response, energy production, and immune function. Demonstrating that the problem originates centrally (brain) rather than peripherally (adrenal glands) shifted understanding of ME/CFS pathophysiology and opened investigation into neurochemical deficiencies that might underlie fatigue and other symptoms.
This study does not establish that HPA axis dysfunction causes ME/CFS symptoms or that correcting cortisol levels will resolve the condition. The normal CSF CRH levels suggest the mechanism may not be simple CRH deficiency alone, leaving the underlying etiology of the central defect undetermined. Additionally, cross-sectional design cannot establish causality or temporal relationships.
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
Demitrack, M A, Dale, J K, Straus, S E, Laue, L, Listwak, S J, Kruesi, M J, et al. (1991). Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome.. The Journal of clinical endocrinology and metabolism. https://doi.org/10.1210/jcem-73-6-1224
BibTeX
@article{mecfsatlas-demitrack-1991-evidence-impaired,
author = {Demitrack, M A and Dale, J K and Straus, S E and Laue, L and Listwak, S J and Kruesi, M J and Chrousos, G P and Gold, P W},
title = {Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome.},
journal = {The Journal of clinical endocrinology and metabolism},
year = {1991},
doi = {10.1210/jcem-73-6-1224},
note = {PubMed: 1659582},
url = {https://www.mecfsatlas.com/evidence/demitrack-1991-evidence-impaired},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/demitrack-1991-evidence-impaired
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