Normal opioid tone and hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome despite marked functional impairment

Abstract

Objective: To determine whether the functional impairment seen in chronic fatigue syndrome (CFS) is associated with reduced levels of central opioids and/or deficiency of the hypothalamic-pituitary-adrenal (HPA) axis.

Design: Single-blinded case-control study measuring functional and psychological status, basal hormonal parameters and ACTH/cortisol response to naloxone and ovine corticotrophin-releasing hormone (oCRH) vs. placebo in people with CFS and healthy controls.

Patients: Twelve people with CFS and 11 age-matched controls.

Measurements: Hormonal parameters: basal levels of 09:00 h plasma cortisol, dehydroepiandrosterone sulfate (DHEAS) and IGF-1. 24-h urinary free cortisol. Plasma ACTH and cortisol response to naloxone 125 microg/kg, oCRH 1 microg/kg and placebo (normal saline). Psychological parameters: SF-36, Hamilton Depression Score, Hospital Anxiety and Depression Scale and Fatigue Scale.

Results: There were highly significant differences between the CFS subjects and the controls with respect to the measures of fatigue and physical functioning. However, there were no differences in basal levels of 09:00 h cortisol (367 +/- 37 vs. 331 +/- 39 nmol/l, P = 0.51), DHEAS (4.2 +/- 0.6 vs. 4.0 +/- 0.5 micromol/l, P = 0.81), 24-h urinary free cortisol (182 +/- 27 vs. 178 +/- 21 nmol/24 h, P = 0.91) or IGF-1 (145 +/- 19 vs. 130 +/- 11 microg/l, P = 0.52) between the CFS group and controls, respectively. There was also no difference between the groups with respect to the ACTH and cortisol response to either oCRH or naloxone.

Conclusions: Our data do not support an aetiological role for deficiency in central opioids or the HPA axis in the symptoms of CFS.