Blunted adrenocorticotropin and cortisol responses to corticotropin-releasing hormone stimulation in chronic fatigue syndrome

Hypofunctioning of the pituitary-adrenal axis has been suggested as the pathophysiological basis for chronic fatigue syndrome (CFS). Blunted adrenocorticotropin (ACTH) responses but normal cortisol responses to exogenous corticotropin-releasing hormone (CRH), the main regulator of this axis, have been previously demonstrated in CFS patients, some of whom had a comorbid psychiatric disorder. We wished to re-examine CRH activation of this axis in CFS patients free from concurrent psychiatric illness. A sample of 14 patients with CDC-diagnosed CFS were compared with 14 healthy volunteers. ACTH and cortisol responses were measured following the administration of 100 mu g ovine CRH. Basal ACTH and cortisol values did not differ between the two groups. The release of ACTH was significantly attenuated in the CFS group (P<0.005), as was the release of cortisol (P<0.05). The blunted response of ACTH to exogenous CRH stimulation may be due to an abnormality in CRH levels with a resultant alteration in pituitary CRH receptor sensitivity, or it may reflect a dysregulation of vasopressin or other factors involved in HPA regulation. A diminished output of neurotrophic ACTH, causing a reduced adrenocortical secretory reserve, inadequately compensated for by adrenoceptor upregulation, may explain the reduced cortisol production demonstrated in this study.