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24-Hour Pituitary and Adrenal Hormone Profiles in Chronic Fatigue Syndrome

From the Department of Neurological and Psychiatric Services, University of Bari, Bari, Italy (A.D.G.); the Section of Neurobiology of Mood Disorders, Division of Psychological Medicine (A.D.G., A.J.C., M.H.) and the Department of Clinical Biochemistry (W.J.), The Institute of Psychiatry and Guy’s, King’s and St Thomas’ School of Medicine, London, UK; and the National Affective Disorders Unit, Bethlem Royal and Maudsley Hospitals, London, UK (A.J.C.).

Address correspondence and reprint requests to Anthony J. Cleare, BSc, MBBS, MRCPsych, PhD, Head, Section of Neurobiology of Mood Disorders, Division of Psychological Medicine, The Institute of Psychiatry, 103 Denmark Hill, London SE5 8AZ, UK. E-mail: a.cleare{at}iop.kcl.ac.uk

Objectives: Disturbances of neuroendocrine function, particularly the hypothalamo–pituitary–adrenal (HPA) axis, have been implicated in the pathophysiology of chronic fatigue syndrome (CFS). However, few studies have attempted to measure blood levels of pituitary or adrenal hormones across a whole 24-hour period in CFS, and those that did so have used infrequent sampling periods. Our aim was to assess 24-hour pituitary and adrenal function using frequent blood sampling.

Methods: We recruited 15 medication-free patients with CFS without comorbid psychiatric disorder and 10 healthy control subjects. Blood samples were collected over 24 hours and assayed for cortisol, corticotropin (ACTH), growth hormone (GH), and prolactin (PRL) levels on an hourly basis during daytime hours (10 am to 10 pm) and every 15 minutes thereafter (10 pm to 10 am).

Results: Repeated-measures analyses of variance were undertaken using hormone levels averaged over 2-hour blocks to smooth curves by reducing the influence of sample timing relative to secretory burst. For ACTH, there was both a main effect of group, suggesting reduced mean ACTH secretion in patients with CFS over the whole monitoring period, and a group-by-time interaction, suggesting a differential pattern of ACTH release. Post hoc analysis showed reduced ACTH levels in CFS during the 8 am to 10 am period. In contrast, there were no significant abnormalities in the levels of cortisol, GH, and PRL in patients with CFS over the full cycle compared with control subjects. Cosinor analysis found no differences in the cortisol circadian rhythm parameters, but the ACTH rhythm did differ, patients with CFS showing an earlier acrophase.

Conclusions: Patients with CFS demonstrated subtle alterations in HPA axis activity characterized by reduced ACTH over a full circadian cycle and reduced levels during the usual morning physiological peak ACTH secretion. This provides further evidence of subtle dysregulation of the HPA axis in CFS. Whether this dysregulation is a primary feature of the illness or instead represents a biologic effect secondary to having the illness itself remains unclear.

Key Words: chronic fatigue syndrome • neuroendocrinology • cortisol • hypothalamo–pituitary–adrenal axis • ACTH • circadian rhythm

Abbreviations: PRL = prolactin; GH = growth hormone; ACTH = corticotrophin; CFS = chronic fatigue syndrome; HPA = hypothalamo–pituitary–adrenal; BMI = body mass index; CDC = Centers for Disease Control and Prevention; DSM-IV = Diagnostic and Statistical Manual, Fourth Edition; RIA = radioimmunoassay; IRMA = immunoradiometric assay; NETRIA = North East Thames radioimmunoassay; ANOVA = analysis of variance; CV = coefficient of variance; MESOR = midline estimate statistic of rhythm; CRH = corticotrophin-releasing hormone; CI = confidence interval; SD = standard deviation.

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