The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome.
Tanriverdi, F, Karaca, Z, Unluhizarci, K et al. · Stress (Amsterdam, Netherlands) · 2007 · DOI
Quick Summary
This review examines how the stress response system (called the HPA axis) works differently in people with ME/CFS and fibromyalgia. The HPA axis is normally responsible for managing how your body responds to stress. Most studies show that in these conditions, the system is underactive and produces lower levels of cortisol (a stress hormone), though some studies have found different results.
Why It Matters
Understanding HPA axis dysfunction is crucial for ME/CFS because it may explain why standard stress-response hormones are abnormal in this disease, potentially informing treatment approaches. If the low cortisol is the body's adaptive response rather than a defect, it changes how researchers think about whether to treat this finding and how.
Observed Findings
Most studies demonstrate HPA axis hypoactivity and hypocortisolemia in ME/CFS and fibromyalgia patients
No structural abnormalities of the hypothalamus, pituitary gland, or adrenal glands have been detected
Some contradictory results exist regarding the direction and magnitude of HPA axis alterations
HPA axis dysfunction is also found in other stress-related disorders (chronic pelvic pain, post-traumatic stress disorder)
Variations in findings correlate with differences in patient selection, assessment methodology, and disease stage at testing
Inferred Conclusions
HPA axis hypoactivity in stress-related disorders appears to be functional rather than structural in nature
Low cortisol levels in ME/CFS and fibromyalgia may represent an adaptive physiological response to chronic stress rather than a pathogenic defect
Inconsistencies in HPA axis findings across studies reflect methodological and patient selection differences rather than fundamental disagreement about dysfunction presence
Standardized protocols for HPA axis assessment are needed to clarify the exact nature of axis alterations in these conditions
Remaining Questions
Does HPA axis underactivity cause disease symptoms, or does chronic illness cause the axis dysfunction?
What This Study Does Not Prove
This review does not establish causation—whether HPA axis underactivity causes ME/CFS symptoms or results from the chronic illness itself. It also cannot definitively resolve contradictory findings in the literature or determine which testing methods are most accurate. The study does not prove that HPA axis dysfunction is the primary mechanism driving ME/CFS pathology.