Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome.
Jerjes, Walid K, Peters, Timothy J, Taylor, Norman F et al. · Journal of psychosomatic research · 2006 · DOI
Quick Summary
This study measured stress hormone levels in urine samples from ME/CFS patients and healthy people throughout the day. Researchers found that ME/CFS patients had lower levels of certain stress hormones (cortisol and cortisone) compared to healthy controls, though the daily pattern of these hormones was normal. Interestingly, when they looked at other related hormone measurements, they didn't see the same difference, which suggests the stress response system may not be working as hard in ME/CFS.
Why It Matters
Understanding the hormonal basis of ME/CFS is crucial for developing targeted treatments and validating the biological nature of the disease. This study provides objective evidence of altered stress hormone physiology in carefully characterized patients, helping establish that ME/CFS involves measurable biological changes rather than being primarily psychological. These findings could guide future research into whether restoring normal HPA function might improve symptoms.
Observed Findings
ME/CFS patients had significantly lower urinary free cortisol concentrations throughout the 24-hour cycle compared to controls.
Urinary cortisone levels were also significantly reduced in CFS patients while maintaining a normal diurnal rhythm.
Cortisol metabolite concentrations and metabolite ratios were not significantly different between CFS and control groups at any time point.
Both groups showed normal diurnal rhythm patterns (higher in morning, lower in evening).
The timing of the diurnal rhythm was similar between CFS patients and controls.
Inferred Conclusions
CFS involves reduced basal HPA axis function as evidenced by lower free cortisol and cortisone levels.
The reduced cortisol and cortisone are not explained by altered circadian rhythm timing.
The discrepancy between free steroid reduction and normal metabolite levels suggests possible HPA axis dysfunction at a specific physiological level rather than global impairment.
CFS patients with uncomplicated presentation (no medications, no psychiatric comorbidity) show measurable neuroendocrine alterations.
Remaining Questions
Why do free cortisol and cortisone levels differ from metabolite measures, and what does this discrepancy reveal about the specific site of HPA axis dysfunction?
What This Study Does Not Prove
This study does not establish whether low cortisol causes ME/CFS symptoms or results from the illness. The conflicting results between free cortisol and metabolite measures mean the authors cannot definitively conclude the exact nature of HPA axis dysfunction. The cross-sectional design cannot determine causality, and the findings apply only to unmedicated patients without psychiatric comorbidities, limiting generalizability.
Does reduced cortisol contribute to ME/CFS symptoms, or is it a consequence of the disease process?
How do these findings apply to ME/CFS patients with comorbid psychiatric conditions or those taking medications that affect the HPA axis?
Does HPA axis function change over the course of illness, and might it differ between CFS patients with different symptom profiles or disease severity?