E3 PreliminaryPreliminaryPEM unclearReview-NarrativePeer-reviewedMachine draft
The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome.
Crofford, L J · Zeitschrift fur Rheumatologie · 1998 · DOI
Quick Summary
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.
Why It Matters
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.
Observed Findings
- HPA axis abnormalities are present in fibromyalgia and chronic fatigue syndrome
- Common treatments for these conditions (exercise, tricyclic antidepressants, SSRIs) affect HPA axis function
- Symptoms in FM and CFS (pain, fatigue, sleep disturbance, psychological distress) are also seen in other disorders with HPA axis disturbances
- HPA axis dysfunction appears across multiple stress-related syndromes, not only FM/CFS
Inferred Conclusions
- There may be a relationship between abnormal HPA axis function and the clinical manifestations of FM and CFS
- Both basal (resting) and dynamic (responsive) HPA axis function warrant investigation in relation to symptom expression
- Therapeutic interventions in these conditions may work partly through normalizing HPA axis function
Remaining Questions
- Which specific HPA axis abnormalities (cortisol levels, ACTH response, etc.) correlate with individual symptom clusters?
- Does correcting HPA axis dysfunction directly improve patient symptoms, or is improvement indirect?
- Are HPA axis abnormalities a primary cause of ME/CFS or a secondary consequence of chronic illness?
What This Study Does Not Prove
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.
Tags
Symptom:Cognitive DysfunctionUnrefreshing SleepPainFatigue
Biomarker:Blood Biomarker
Method Flag:Weak Case DefinitionExploratory Only
Metadata
- DOI
- 10.1007/s003930050239
- PMID
- 10025087
- Review status
- Machine draft
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 8 April 2026
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 →
Spotted an error in this entry? Report it →