Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites 
in chronic fatigue syndrome

Journal of Psychosomatic Research, Volume 60, Issue 2, February 
2006, Pages 145-153

Walid K. Jerjes [a, *], Timothy J. Peters [a], Norman F. Taylor 
[a], Peter J. Wood [b], Simon Wessely [c] and Anthony J. Cleare [d, e]

Affiliations:
[a] Department of Clinical Biochemistry, Guy's, King's and St Thomas' 
School of Medicine, Bessemer Road, SE5 9RS London, UK
[b] Regional Endocrine Unit, Southampton General Hospital, SO16 6YD 
Southampton, UK
[c] Section of General Hospital Psychiatry, Division of Psychological 
Medicine, Institute of Psychiatry, King's College London, De Crespigny 
Park, SE5 8AF London, UK
[d] Section of Neurobiology of Mood Disorders, Division of Psychological 
Medicine, Institute of Psychiatry, King's College London, De Crespigny 
Park, SE5 8AF London, UK
[e] National Affective Disorders Unit, Bethlem Royal and Maudsley 
Hospitals, Monk's Orchard Road, Beckenham, BR3 3BS Kent, UK

[*] Corresponding author. Tel.: +44 020 7346 4131; fax: +44 0207 737 7434. 
E-mail: jerjes@kcl.ac.uk

Received 3 February 2005;  revised 5 July 2005;  accepted 19 July 
2005.  Available online 24 January 2006.


Abstract
Objective: The aim of this study was to obtain comprehensive information on 
basal hypothalamic-pituitary-adrenal (HPA) axis activity in chronic fatigue 
syndrome (CFS) patients who were not affected by medication or comorbid 
psychiatric disorder likely to influence the HPA axis.

Method: Steroid analysis of urine collections from 0600 to 2100 h at 3-h 
intervals in CFS patients and in controls.

Results: Urinary free cortisol and cortisone concentrations showed a 
significant normal diurnal rhythm, but levels were lower across the cycle 
in CFS. In contrast, while urinary cortisol metabolites also showed a 
normal diurnal rhythm, levels were not significantly different between the 
CFS and controls at any time. Derived metabolite ratios were similar in 
both groups.

Conclusion: This study provides further evidence for reduced basal HPA axis 
function in patients with CFS, based on lower free cortisol and cortisone 
levels, but this is not corroborated by cortisol metabolite data. The 
difference between these measures cannot be explained by an altered timing 
of the diurnal rhythm.


Keywords: Chronic fatigue syndrome (CFS); Diurnal rhythm; Metabolism; 
Urinary cortisol; Urinary cortisone