Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome.
Van Den Eede, Filip, Moorkens, Greta, Van Houdenhove, Boudewijn et al. · Neuropsychobiology · 2007 · DOI
Quick Summary
This review examined research on the stress-response system (called the HPA axis) in ME/CFS patients. Scientists found that many people with ME/CFS have lower-than-normal stress hormone levels and don't respond typically to stress. While it's unclear whether this hormone imbalance causes ME/CFS or develops because of it, the authors suggest it likely plays a role in how symptoms develop and persist.
Why It Matters
Understanding HPA axis dysfunction in ME/CFS may explain why patients often feel unable to mount appropriate stress responses and may inform treatment approaches targeting hormone regulation. This review consolidates fragmented evidence and identifies whether hormone abnormalities are a core feature or secondary consequence, which is essential for developing targeted interventions.
Observed Findings
Mild hypocortisolism (lower-than-normal cortisol levels) observed in a proportion of ME/CFS patients
Blunted adrenocorticotropin (ACTH) response to physical and psychological stressors
Enhanced negative feedback sensitivity to glucocorticoids, indicating altered hormone regulation
Methodological variation and inconsistency across studies examining HPA function
Inferred Conclusions
HPA axis hypofunction is present in at least a subset of ME/CFS patients, characterized by reduced cortisol and blunted stress hormone responses
Whether HPA dysfunction is primary or secondary to other pathophysiological mechanisms remains unclear
Even if secondary, HPA axis abnormalities likely contribute to symptom propagation and maintenance in ME/CFS
Remaining Questions
Is HPA axis dysfunction a primary pathogenic factor in ME/CFS or a secondary consequence of other biological disturbances?
Does HPA dysfunction occur uniformly across all ME/CFS patients or only in specific patient subgroups?
What are the specific underlying mechanisms driving HPA hypofunction—immune activation, central sensitivity, genetic factors, or others?
What This Study Does Not Prove
This review does not prove that HPA axis dysfunction causes ME/CFS or that it occurs in all patients with the condition. The authors explicitly note methodological difficulties across studies and that the causal relationship remains unresolved—HPA abnormalities could be secondary to other disease mechanisms rather than primary drivers.