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Vol. 55, No. 2, 2007
Issue release date: July 2007
Editor's Choice -- Free Access
Neuropsychobiology 2007;55:112–120
(DOI:10.1159/000104468)

Hypothalamic-Pituitary-Adrenal Axis Function in Chronic Fatigue Syndrome

Van Den Eede F.a, c, d · Moorkens G.b · Van Houdenhove B.e · Cosyns P.a, c · Claes S.J.d, e
Departments of aPsychiatry and bInternal Medicine, University Hospital Antwerp, Edegem, cCollaborative Antwerp Psychiatric Research Institute, University of Antwerp, dDepartment of Molecular Genetics VIB8, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, and eDepartment of Psychiatry, University Hospital Gasthuisberg, Leuven, Belgium
email Corresponding Author

Abstract

There is evidence for a hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis in a proportion of the patients with chronic fatigue syndrome (CFS), despite the negative studies and methodological difficulties. In this review, we focus on challenge studies and on the role of the HPA axis in the pathogenesis of CFS. Mild hypocortisolism, blunted adrenocorticotropin response to stressors and enhanced negative feedback sensitivity to glucocorticoids are the main findings. Several underlying mechanisms have been proposed. Currently, it is a matter of debate whether these disturbances have a primary role in the pathogenesis of CFS. However, even if the HPA axis dysfunctions are secondary to other factors, they are probably a relevant factor in symptom propagation in CFS.


 goto top of outline Key Words

  • Challenge test
  • Cortisol
  • Corticotropin-releasing factor
  • Fatigue
  • Neuroendocrinology
  • Stress

 goto top of outline Abstract

There is evidence for a hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis in a proportion of the patients with chronic fatigue syndrome (CFS), despite the negative studies and methodological difficulties. In this review, we focus on challenge studies and on the role of the HPA axis in the pathogenesis of CFS. Mild hypocortisolism, blunted adrenocorticotropin response to stressors and enhanced negative feedback sensitivity to glucocorticoids are the main findings. Several underlying mechanisms have been proposed. Currently, it is a matter of debate whether these disturbances have a primary role in the pathogenesis of CFS. However, even if the HPA axis dysfunctions are secondary to other factors, they are probably a relevant factor in symptom propagation in CFS.

Copyright © 2007 S. Karger AG, Basel


 goto top of outline References
  1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A: The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994;121:953–959.
  2. Cleare AJ: The neuroendocrinology of chronic fatigue syndrome. Endocr Rev 2003;24:236–252.
  3. Poteliakhoff A: Adrenocortical activity and some clinical findings in acute and chronic fatigue. J Psychosom Res 1981;25:91–95.
  4. Afari N, Buchwald D: Chronic fatigue syndrome: a review. Am J Psychiatry 2003;160:221–236.
  5. Hatcher S, House A: Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study. Psychol Med 2003;33:1185–1192.
  6. Heim C, Wagner D, Maloney E, Papanicolaou DA, Solomon L, Jones JF, Unger ER, Reeves WC: Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Arch Gen Psychiatry 2006;63:1258–1266.
  7. Kato K, Sullivan PF, Evengard B, Pedersen NL: Premorbid predictors of chronic fatigue. Arch Gen Psychiatry 2006;63:1267–1272.
  8. Prins JB, van der Meer JW, Bleijenberg G: Chronic fatigue syndrome. Lancet 2006;367:346–355.
  9. Theorell T, Blomkvist V, Lindh G, Evengard B: Critical life events, infections, and symptoms during the year preceding chronic fatigue syndrome (CFS): an examination of CFS patients and subjects with a nonspecific life crisis. Psychosom Med 2005;61:304–310.
  10. Van Houdenhove B, Neerinckx E, Lysens R, Vertommen H, Van Houdenhove L, Onghena P, Westhovens R, D’Hooghe MB: Victimization in chronic fatigue syndrome and fibromyalgia in tertiary care: a controlled study on prevalence and characteristics. Psychosomatics 2001;42:21–28.
  11. Van Houdenhove B, Neerinckx E, Onghena P, Lysens R, Vertommen H: Premorbid ‘overactive’ lifestyle in chronic fatigue syndrome and fibromyalgia. An etiological factor or proof of good citizenship? J Psychosom Res 2001;51:571–576.
  12. Fries E, Hesse J, Hellhammer J, Hellhammer DH: A new view on hypocortisolism. Psychoneuroendocrinology 2005;30:1010–1016.
  13. Gold PW, Chrousos GP: Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 2002;7:254–275.
  14. Heim C, Ehlert U, Hellhammer DH: The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 2000;25:1–35.
  15. Parker AJ, Wessely S, Cleare AJ: The neuroendocrinology of chronic fatigue syndrome and fibromyalgia. Psychol Med 2001;31:1331–1345.
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  17. Jerjes WK, Peters TJ, Taylor NF, Wood PJ, Wessely S, Cleare AJ: Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome. J Psychosom Res 2006;60:145–153.
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  19. Di Giorgio A, Hudson M, Jerjes W, Cleare AJ: 24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome. Psychosom Med 2005;67:433–440.
  20. Demitrack MA, Dale JK, Straus SE, Laue L, Listwak SJ, Kruesi MJ, Chrousos, GP, Gold PW: Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab 1991;73:1224–1234.
  21. Demitrack MA, Crofford LJ: Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann NY Acad Sci 1998;840:684– 697.
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  82. Cleare AJ, Heap E, Malhi GS, Wessely S, O’Keane V, Miell J: Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet 1999;353:455–458.
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 goto top of outline Author Contacts

Filip Van Den Eede, PhD
Department of Psychiatry, University Hospital Antwerp (UZA)
Wilrijkstraat 10
BE–2650 Edegem (Belgium)
Tel. +32 3 821 49 11, Fax +32 3 825 16 41, E-Mail filip.van.den.eede@uza.be


 goto top of outline Article Information

Received: August 29, 2006
Accepted after revision: March 17, 2007
Published online: June 27, 2007
Number of Print Pages : 9
Number of Figures : 1, Number of Tables : 1, Number of References : 83


 goto top of outline Publication Details

Neuropsychobiology (International Journal of Experimental and Clinical Research in Biological Psychiatry, Pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography)

Vol. 55, No. 2, Year 2007 (Cover Date: July 2007)

Journal Editor: Strik, W. (Bern)
ISSN: 0302–282X (print), 1423–0224 (Online)

For additional information: http://www.karger.com/NPS


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

There is evidence for a hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis in a proportion of the patients with chronic fatigue syndrome (CFS), despite the negative studies and methodological difficulties. In this review, we focus on challenge studies and on the role of the HPA axis in the pathogenesis of CFS. Mild hypocortisolism, blunted adrenocorticotropin response to stressors and enhanced negative feedback sensitivity to glucocorticoids are the main findings. Several underlying mechanisms have been proposed. Currently, it is a matter of debate whether these disturbances have a primary role in the pathogenesis of CFS. However, even if the HPA axis dysfunctions are secondary to other factors, they are probably a relevant factor in symptom propagation in CFS.



 goto top of outline Author Contacts

Filip Van Den Eede, PhD
Department of Psychiatry, University Hospital Antwerp (UZA)
Wilrijkstraat 10
BE–2650 Edegem (Belgium)
Tel. +32 3 821 49 11, Fax +32 3 825 16 41, E-Mail filip.van.den.eede@uza.be


 goto top of outline Article Information

Received: August 29, 2006
Accepted after revision: March 17, 2007
Published online: June 27, 2007
Number of Print Pages : 9
Number of Figures : 1, Number of Tables : 1, Number of References : 83


 goto top of outline Publication Details

Neuropsychobiology (International Journal of Experimental and Clinical Research in Biological Psychiatry, Pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography)

Vol. 55, No. 2, Year 2007 (Cover Date: July 2007)

Journal Editor: Strik, W. (Bern)
ISSN: 0302–282X (print), 1423–0224 (Online)

For additional information: http://www.karger.com/NPS


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A: The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994;121:953–959.
  2. Cleare AJ: The neuroendocrinology of chronic fatigue syndrome. Endocr Rev 2003;24:236–252.
  3. Poteliakhoff A: Adrenocortical activity and some clinical findings in acute and chronic fatigue. J Psychosom Res 1981;25:91–95.
  4. Afari N, Buchwald D: Chronic fatigue syndrome: a review. Am J Psychiatry 2003;160:221–236.
  5. Hatcher S, House A: Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study. Psychol Med 2003;33:1185–1192.
  6. Heim C, Wagner D, Maloney E, Papanicolaou DA, Solomon L, Jones JF, Unger ER, Reeves WC: Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Arch Gen Psychiatry 2006;63:1258–1266.
  7. Kato K, Sullivan PF, Evengard B, Pedersen NL: Premorbid predictors of chronic fatigue. Arch Gen Psychiatry 2006;63:1267–1272.
  8. Prins JB, van der Meer JW, Bleijenberg G: Chronic fatigue syndrome. Lancet 2006;367:346–355.
  9. Theorell T, Blomkvist V, Lindh G, Evengard B: Critical life events, infections, and symptoms during the year preceding chronic fatigue syndrome (CFS): an examination of CFS patients and subjects with a nonspecific life crisis. Psychosom Med 2005;61:304–310.
  10. Van Houdenhove B, Neerinckx E, Lysens R, Vertommen H, Van Houdenhove L, Onghena P, Westhovens R, D’Hooghe MB: Victimization in chronic fatigue syndrome and fibromyalgia in tertiary care: a controlled study on prevalence and characteristics. Psychosomatics 2001;42:21–28.
  11. Van Houdenhove B, Neerinckx E, Onghena P, Lysens R, Vertommen H: Premorbid ‘overactive’ lifestyle in chronic fatigue syndrome and fibromyalgia. An etiological factor or proof of good citizenship? J Psychosom Res 2001;51:571–576.
  12. Fries E, Hesse J, Hellhammer J, Hellhammer DH: A new view on hypocortisolism. Psychoneuroendocrinology 2005;30:1010–1016.
  13. Gold PW, Chrousos GP: Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 2002;7:254–275.
  14. Heim C, Ehlert U, Hellhammer DH: The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 2000;25:1–35.
  15. Parker AJ, Wessely S, Cleare AJ: The neuroendocrinology of chronic fatigue syndrome and fibromyalgia. Psychol Med 2001;31:1331–1345.
  16. Wood B, Wessely S, Papadopoulos A, Poon L, Checkley S: Salivary cortisol profiles in chronic fatigue syndrome. Neuropsychobiology 1998;37:1–4.
  17. Jerjes WK, Peters TJ, Taylor NF, Wood PJ, Wessely S, Cleare AJ: Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome. J Psychosom Res 2006;60:145–153.
  18. Roberts AD, Wessely S, Chalder T, Papadopoulos A, Cleare AJ: Salivary cortisol response to awakening in chronic fatigue syndrome. Br J Psychiatry 2004;184:136–141.
  19. Di Giorgio A, Hudson M, Jerjes W, Cleare AJ: 24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome. Psychosom Med 2005;67:433–440.
  20. Demitrack MA, Dale JK, Straus SE, Laue L, Listwak SJ, Kruesi MJ, Chrousos, GP, Gold PW: Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab 1991;73:1224–1234.
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