E2 ModeratePreliminaryPEM not requiredCross-SectionalPeer-reviewedReviewed
Salivary cortisol profiles in chronic fatigue syndrome.
Wood, B, Wessely, S, Papadopoulos, A et al. · Neuropsychobiology · 1998 · DOI
Quick Summary
This study measured cortisol (a stress hormone) levels in the saliva of 10 people with ME/CFS and 10 healthy people over a 16-hour period. Contrary to some earlier research, people with ME/CFS actually had slightly higher cortisol levels on average than healthy controls. This finding suggests that low cortisol is not the cause of fatigue in ME/CFS.
Why It Matters
This study challenges the hypothesis that low cortisol causes ME/CFS fatigue, redirecting research toward other biological mechanisms. Understanding cortisol's actual role in ME/CFS is important for developing targeted treatments and for validating or ruling out potential biomarkers.
Observed Findings
- Mean salivary cortisol concentration over 16 hours was significantly greater in CFS patients than matched healthy controls (p < 0.05)
- CFS patients in this cohort did not show hypocortisolaemia (low cortisol state)
- Findings were obtained from 10 CFS patients without concurrent depressive disorder, carefully matched to controls
Inferred Conclusions
- Fatigue in CFS is not caused by cortisol deficiency (hypocortisolaemia)
- Cortisol dysregulation in CFS, if present, may involve mechanisms other than overall reduction in hormone levels
- The earlier reports of low cortisol in CFS may not represent the typical CFS pathophysiology or may apply only to specific subgroups
Remaining Questions
- Does the daily cortisol rhythm (timing and pattern of peaks and troughs) differ between CFS and healthy controls, even if mean levels are elevated?
- Do cortisol levels vary across different CFS patient subgroups, and if so, what factors define these subgroups?
- What other endocrine or neuroendocrine abnormalities might explain fatigue if cortisol deficiency is not the primary cause?
What This Study Does Not Prove
This study does not prove that cortisol plays no role in ME/CFS pathology—elevated levels do not exclude cortisol dysregulation or abnormal cortisol signaling. The finding of higher mean cortisol does not explain the cause of fatigue or identify what dysregulation might be occurring. It also does not apply to CFS patients with concurrent depression, which was excluded.
Tags
Symptom:Fatigue
Biomarker:Blood Biomarker
Method Flag:PEM Not DefinedSmall SampleExploratory OnlyWeak Case Definition
Metadata
- DOI
- 10.1159/000026469
- PMID
- 9438265
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 12 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 →
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