Cleare, A J, Miell, J, Heap, E et al. · The Journal of clinical endocrinology and metabolism · 2001 · DOI
This study examined whether ME/CFS patients have problems with their stress hormone system (called the HPA axis) and whether a low dose of the steroid hormone hydrocortisone could help. Researchers found that ME/CFS patients had lower levels of cortisol (a stress hormone) in their urine and a reduced response to certain hormone challenges, suggesting their adrenal glands may not be producing enough cortisol. When some patients received hydrocortisone treatment, their fatigue improved and their hormone responses normalized.
This study is important because it identifies a potentially treatable endocrine abnormality (reduced adrenal cortisol output) in ME/CFS and demonstrates that low-dose hydrocortisone can restore hormone function and reduce fatigue in a subset of patients. Understanding the HPA axis abnormality helps explain some of ME/CFS's physiological basis and may guide personalized treatment approaches.
This study does not prove that HPA axis dysfunction causes ME/CFS—the abnormality could be secondary to other disease mechanisms. It also does not demonstrate that all ME/CFS patients will benefit from hydrocortisone, nor does it address long-term safety and efficacy of this treatment. The mechanism explaining why some patients respond and others do not remains unknown.
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
Cleare, A J, Miell, J, Heap, E, Sookdeo, S, Young, L, Malhi, G S, et al. (2001). Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy.. The Journal of clinical endocrinology and metabolism. https://doi.org/10.1210/jcem.86.8.7735
BibTeX
@article{mecfsatlas-cleare-2001-hypothalamo-pituitary,
author = {Cleare, A J and Miell, J and Heap, E and Sookdeo, S and Young, L and Malhi, G S and O'Keane, V},
title = {Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy.},
journal = {The Journal of clinical endocrinology and metabolism},
year = {2001},
doi = {10.1210/jcem.86.8.7735},
note = {PubMed: 11502777},
url = {https://www.mecfsatlas.com/evidence/cleare-2001-hypothalamo-pituitary},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/cleare-2001-hypothalamo-pituitary
Contribute
Private, reviewed by a human. Not a public comment thread.