Van Houdenhove, Boudewijn, Van Den Eede, Filip, Luyten, Patrick · Medical hypotheses · 2009 · DOI
This study explores why many ME/CFS patients have problems with their stress hormone system, particularly a gland in the brain called the hypothalamus. The researchers suggest that ME/CFS might involve a breakdown in how the body normally responds to stress, leading to an imbalance that triggers excessive inflammation and sickness symptoms like exhaustion and pain sensitivity.
Understanding the mechanisms behind HPA axis dysfunction could help clinicians recognize ME/CFS as a distinct neuroendocrine-immune disorder and move beyond viewing it as primarily psychological. If validated, this framework could direct research toward the immune-endocrine interface and inform development of mechanism-targeted therapies rather than generic fatigue treatments.
This theoretical review does not establish causation or present new experimental evidence—it synthesizes existing literature and proposes a hypothesis. The study cannot definitively prove that HPA dysfunction causes ME/CFS symptoms or explain the relative contributions of stress system dysregulation versus other potential pathogenic factors. The authors acknowledge uncertainty about whether neuroendocrine disturbances are primary drivers or secondary consequences of illness.
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
Van Houdenhove, Boudewijn, Van Den Eede, Filip, & Luyten, Patrick (2009). Does hypothalamic-pituitary-adrenal axis hypofunction in chronic fatigue syndrome reflect a 'crash' in the stress system?. Medical hypotheses. https://doi.org/10.1016/j.mehy.2008.11.044
BibTeX
@article{mecfsatlas-van-houdenhove-2009-does-hypothalamic,
author = {Van Houdenhove, Boudewijn and Van Den Eede, Filip and Luyten, Patrick},
title = {Does hypothalamic-pituitary-adrenal axis hypofunction in chronic fatigue syndrome reflect a 'crash' in the stress system?},
journal = {Medical hypotheses},
year = {2009},
doi = {10.1016/j.mehy.2008.11.044},
note = {PubMed: 19237251},
url = {https://www.mecfsatlas.com/evidence/van-houdenhove-2009-does-hypothalamic},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/van-houdenhove-2009-does-hypothalamic
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