Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome

OBJECTIVE Enhancement of negative feedback control of the HPA axis in patients with chronic fatigue syndrome (CFS) has been reported using the low dose dexamethasone suppression test. We have developed the use of prednisolone (5mg) as a more physiologically appropriate alternative to dexamethasone in the investigation of mild degrees of glucocorticoid resistance or supersensitivity. The objective of the study was to use this test to look for alterations in negative feedback control of the HPA axis in CFS patients. METHODS Fifteen patients with CFS were recruited after fulfilling strict criteria including the absence of comorbid psychiatric diagnosis. They collected urine between 0900 and 1800h and saliva at 0900h pre-prednisolone. At midnight, they took prednisolone (5mg) orally and then collected urine and saliva at the same intervals the following day. RESULTS Salivary cortisol was lower in CFS subjects pre-prednisolone than controls. Urinary cortisol metabolites were lower in CFS subjects pre-prednisolone, but did not reach significance. Both measures were significantly lower in CFS subjects post-dose. Mean percentage suppression of both salivary cortisol and urinary cortisol metabolites was significantly higher in CFS compared to controls. CONCLUSION There is enhanced sensitivity of the HPA axis to negative feedback in CFS as demonstrated using the prednisolone suppression test. This provides further evidence of alterations in the control of the HPA axis in patients with established CFS.

[1]  Ian Hickie,et al.  The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study , 1994, Annals of Internal Medicine.

[2]  M. Stein,et al.  Enhanced Dexamethasone Suppression of Plasma Cortisol in Adult Women Traumatized by Childhood Sexual Abuse , 1997, Biological Psychiatry.

[3]  G. Chrousos,et al.  The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. , 1999, Proceedings of the Association of American Physicians.

[4]  J. Dunn,et al.  Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma. , 1981, The Journal of clinical endocrinology and metabolism.

[5]  A. Cleare,et al.  Plasma leptin in chronic fatigue syndrome and a placebo‐controlled study of the effects of low‐dose hydrocortisone on leptin secretion , 2001, Clinical endocrinology.

[6]  Simon Wessely,et al.  Chronic Fatigue Syndrome , 1996, BMJ : British Medical Journal.

[7]  E. Giller,et al.  Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without posttraumatic stress disorder. , 1995, Archives of general psychiatry.

[8]  S. Wessely,et al.  Urinary Cortisol and Cortisol Metabolite Excretion in Chronic Fatigue Syndrome , 2006, Psychosomatic medicine.

[9]  M. Joëls,et al.  Brain corticosteroid receptor balance in health and disease. , 1998, Endocrine reviews.

[10]  W. Kuis,et al.  Disturbed neuroendocrine-immune interactions in chronic fatigue syndrome. , 2000, The Journal of clinical endocrinology and metabolism.

[11]  S. Wessely,et al.  Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome. , 2006, Journal of psychosomatic research.

[12]  D. Hellhammer,et al.  Abuse-Related Posttraumatic Stress Disorder and Alterations of the Hypothalamic-Pituitary-Adrenal Axis in Women With Chronic Pelvic Pain , 1998, Psychosomatic medicine.

[13]  S. Bourgeois,et al.  Expression of an mdr gene is associated with a new form of resistance to dexamethasone-induced apoptosis. , 1993, Molecular endocrinology.

[14]  G. Huston.  The Hospital Anxiety and Depression Scale. , 1987, The Journal of rheumatology.

[15]  E. D. de Kloet,et al.  CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone. , 1998, The Journal of infectious diseases.

[16]  V. Kostic,et al.  Prolonged psychological stress suppresses cortisol secretion , 2003, Clinical endocrinology.

[17]  S. Wessely,et al.  Diurnal patterns of salivary cortisol and cortisone output in chronic fatigue syndrome. , 2005, Journal of affective disorders.

[18]  R. Yehuda,et al.  Basal cortisol, dexamethasone suppression of cortisol, and MHPG in adolescents after the 1988 earthquake in Armenia. , 1996, The American journal of psychiatry.

[19]  G. Chrousos,et al.  Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. , 1997, Neuroimmunomodulation.

[20]  M. Demitrack,et al.  Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. , 1991, The Journal of clinical endocrinology and metabolism.

[21]  S. Wessely,et al.  Chronic fatigue syndrome. A practical guide to assessment and management. , 1997, General hospital psychiatry.

[22]  I. Hickie,et al.  The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. , 1994, Annals of internal medicine.

[23]  B. Kudielka,et al.  Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. , 1999, Psychosomatic medicine.

[24]  C. Kirschbauma,et al.  Awakening cortisol responses are influenced by health status and awakening time but not by menstrual cycle phase , 2002 .

[25]  J. Thompson.  Behavioural Psychotherapy: Maudsley Pocket Book of Clinical Management. , 1992 .

[26]  J. Amsterdam,et al.  Neuroendocrine Aspects of Chronic Fatigue Syndrome , 2004, Neuroimmunomodulation.

[27]  S. Wessely,et al.  Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial , 1999, The Lancet.

[28]  Ulrike Ehlert,et al.  Low-Dose Dexamethasone Suppression Test in Chronic Fatigue Syndrome and Health , 2002, Psychosomatic medicine.

[29]  D. Murphy,et al.  Reduced Sensitivity to Glucocorticoid Feedback and Reduced Glucocorticoid Receptor mRNA Expression in the Luteal Phase of the Menstrual Cycle , 1997, Neuropsychopharmacology.

[30]  W. Drake,et al.  Modulation of cortisol metabolism by the growth hormone receptor antagonist pegvisomant in patients with acromegaly. , 2001, The Journal of clinical endocrinology and metabolism.

[31]  R. Snaith,et al.  The Hospital Anxiety and Depression Scale , 1983 .

[32]  M. Melamed,et al.  Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[33]  B. Carroll,et al.  Dexamethasone metabolism in dexamethasone suppression test suppressors and nonsuppressors , 2000, Biological Psychiatry.

[34]  A. Cleare,et al.  Assessment of subtle changes in glucocorticoid negative feedback using prednisolone: comparison of salivary free cortisol and urinary cortisol metabolites as endpoints. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[35]  K. Nas,et al.  Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones , 2004, BMC musculoskeletal disorders.

[36]  Daniel J Buysse,et al.  The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research , 1989, Psychiatry Research.

[37]  R. Abs,et al.  Effect of growth hormone treatment in patients with chronic fatigue syndrome: a preliminary study. , 1998, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[38]  S. Wessely,et al.  Development of a fatigue scale. , 1993, Journal of psychosomatic research.

[39]  B. Kudielka,et al.  Awakening cortisol responses are influenced by health status and awakening time but not by menstrual cycle phase , 2003, Psychoneuroendocrinology.

[40]  M. Demitrack,et al.  Abnormalities in response to vasopressin infusion in chronic fatigue syndrome , 2001, Psychoneuroendocrinology.

[41]  E. Lentjes,et al.  Increased Sensitivity to Glucocorticoids in Peripheral Blood Mononuclear Cells of Chronic Fatigue Syndrome Patients, Without Evidence for Altered Density or Affinity of Glucocorticoid Receptors , 2001, Journal of Investigative Medicine.

[42]  M. Hotopf,et al.  Predictors of fatigue following the onset of infectious mononucleosis , 2003, Psychological Medicine.

[43]  C. Kirschbaum,et al.  Burnout, perceived stress, and cortisol responses to awakening. , 1999, Psychosomatic medicine.

[44]  R. Snaith,et al.  The hospital anxiety and depression scale. , 2013, Acta psychiatrica Scandinavica.

[45]  A. Cleare,et al.  The neuroendocrinology of chronic fatigue syndrome. , 2003, Endocrine reviews.