There may be a connection between chronic fatigue syndrome (CFS) and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Research has shown that many patients with CFS exhibit altered stress-hormone signaling rather than classic adrenal failure.
CFS is defined as a persistent or relapsing debilitating fatigue lasting at least six months and is often accompanied by symptoms such as low-grade fevers, arthralgias, myalgias, painful lymph nodes, post-exertional fatigue, neuropsychological complaints, and sleep disturbances. A review article published in Annals of Medicine (1994) reported that only one of sixteen CFS patients showed suppression on dexamethasone testing. Similar findings have been reported in fibromyalgia, where fewer than 5% of patients show suppression.
Several studies have found that individuals with CFS tend to have lower basal cortisol levels or blunted cortisol responses to stress when compared with healthy controls. This pattern overlaps with symptoms seen in relative glucocorticoid insufficiency, including profound fatigue, increased inflammatory symptoms, allergic flares, and disturbances of mood and sleep—particularly following a physiological stressor.
One proposed trigger for this pattern is infection. Viral illnesses such as Epstein–Barr virus (EBV), cytomegalovirus (CMV), and others have been investigated as possible initiating stressors. Earlier work, including a hypothesis paper published in Medical Hypotheses (1991), noted that cortisol levels may decline during certain infections, potentially altering immune regulation.
Research published in the Journal of Clinical Endocrinology and Metabolism (1991) reported reduced cortisol levels in a subset of patients with CFS and cautioned against the routine use of cortisol therapy, noting that exogenous steroids may further suppress endogenous adrenal signaling.
