Abstract
Since the introduction of operationalized criteria, there has been considerable interest in the pathophysiology of chronic fatigue syndrome (CFS). There is an increasing volume of evidence to support the view that patients with this syndrome have unique neuroendocrinology patterns. Central to this endocrine dysfunction is altered hypothalamic-pituitary-adrenal axis (HPA) activity. The cardinal findings include attenuated adrenocorticotrophic hormone (ACTH) responses to corticotropin-releasing hormone (CRH) and low 24-hour urinary cortisol. These are compatible with a mild central adrenal insufficiency. Adrenal steroids have widespread impact in the brain, and of particular importance is their dense concentration on serotonergic and noradrenergic neurotransmitter pathways. Using a variety of different challenge drugs, a supersensitivity of the serotonergic 5-HT 1A receptor has been demonstrated although the results have not been entirely consistent. A blunting of dexamethasone-induced growth hormone release has been described and may reflect a relative subsensitivity of the steroid receptor. It is proposed that the disruption of the HPA, which may be triggered by a number of stressors including infections, may represent a primary phenomenon, and that the neurotransmitter abnormalities described are in fact secondarily heralded by prolonged HPA dysregulation.