The neuroendocrinology of chronic fatigue syndrome and fibromyalgia

Background. Disturbance of the HPA axis may be important in the pathophysio logy of chronic fatigue syndrome (CFS) and fibromyalgia. Symptoms may be du e to: (1) low circulating cortisol; (2) disturbance of central neurotransmi tters; or (3) disturbance of the relationship between cortisol and central neurotransmitter function. Accumulating evidence of the complex relationshi p between cortisol and 5-HT function, make some form of hypothesis (3) most likely. We review the methodology and results of studies of the HPA and ot her neuroendocrine axes in CFS. Method. Medline, Embase and Psychlit were searched using the Cochrane Colla boration strategy. A search was also performed on the King's College CFS da tabase, which includes over 3000 relevant references, and a citation analys is was run on the key paper (Demitrack et al. 1991). Results. One-third of the studies reporting baseline cortisol found it to b e significantly low, usually in one-third of patients. Methodological diffe rences may account for some of the varying results. More consistent is the finding, of reduced HPA function, and enhanced 5-HT function on neuroendocr ine challenge tests. The opioid system, and arginine vasopressin (AVP) may also be abnormal, though the growth hormone (GH) axis appears to be intact, in CFS. Conclusions. The significance of these changes, remains unclear. We have li ttle understanding of how neuroendocrine changes relate to the experience o f symptoms, and it is unclear whether these changes are primary, or seconda ry to behavioural changes in sleep or exercise. Longitudinal studies of pop ulations at risk for CFS will help to resolve these issues.