Crofford, L J · Zeitschrift fur Rheumatologie · 1998 · DOI
This review examines the stress response system (HPA axis) in fibromyalgia and chronic fatigue syndrome. The authors suggest that problems with this stress system may be connected to common symptoms like pain, exhaustion, sleep problems, and mood changes. Several treatments that help patients—including exercise and certain antidepressants—appear to work partly by affecting this stress response system.
Understanding the role of the HPA axis in ME/CFS is crucial because it provides a potential biological mechanism explaining multiple symptoms simultaneously. If HPA dysfunction is central to the disease, it could guide development of targeted treatments and explain why some existing therapies help certain patients.
This review does not establish causality—that HPA axis abnormalities directly cause ME/CFS symptoms. It does not prove which specific HPA perturbations matter most for individual patients, and the presence of HPA changes in multiple stress-related disorders means this finding is not unique to ME/CFS.
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, L J (1998). The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome.. Zeitschrift fur Rheumatologie. https://doi.org/10.1007/s003930050239
BibTeX
@article{mecfsatlas-crofford-1998-hypothalamic-pituitary,
author = {Crofford, L J},
title = {The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome.},
journal = {Zeitschrift fur Rheumatologie},
year = {1998},
doi = {10.1007/s003930050239},
note = {PubMed: 10025087},
url = {https://www.mecfsatlas.com/evidence/crofford-1998-hypothalamic-pituitary},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/crofford-1998-hypothalamic-pituitary
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