Abnormal glandular functions & Abnormal HPA axis (Hypothalmus Pituary Adrenal axis)

(a) Shrunken adrenal glands and low hormone output

(b) Abnormal HPA axis (Hypothalmus Pituary Adrenal axis)

 

(a) Shrunken adrenal glands and low hormone output.

The result of excessive pressure or strain on the adrenal glands over time.

  • Scott LV, The J, Reznek R, Martin A, Sohaib A, Dinan TG. 1999 Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study. Endocrinology 24:759-768.
  • "There are striking similarities between chronic fatigue syndrome and Addison's disease, which share 26 features, including all of the neuropsychological symptoms"
    Canadian Medical Association Journal
    http://www.cma.ca/cmaj/vol-160/issue-5/0636a.htm
  • Professor Ted Dinan and Dr. Lucinda Scott, St. Batholomew's Hospital, London. Radiology, 1998, 209 (supl) 411-412.

  • De Becker P, Roeykens J, Reynders M, Mc Gregor N, De Meirleir K. Exercise capacity in chronic fatigue syndrome. Arch Intern Med. 2000;160:3270-3277

  • Bell, David S., M.D. The Doctor’s Guide to Chronic Fatigue Syndrome. 1993 Addison Wesley, pp. 115.

  • Shrunken adrenal glands confirmed by Research at St. James Hospital, Dublin, Ireland, in 2001.

  • Demitrack M, et al. Evidence for impaired activation of the hypothalamic-adrenal-pituitary axis in patients with CFS. J Clin Endocrin Metab 1991;73:1224-34.

  • McKenzie R, et al. Low-dose hydrocortisone for treatment of CFS. JAMA1998;280:1061-66.

  • Scott LV, Dinan TG: Urinary free cortisol excretion in chronic fatigue syndrome, major depression and in healthy volunteers. J Affect Disord 1998, 47:49-54.

  • Scott LV, et al. Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study. Psychoneuroendocrinology 1999;24:759-68.

  • Teitelbaum, Jacob, M.D., From Fatigued to Fantastic: A Manual for Moving Beyond Chronic Fatigue and Fibromyalgia. 1995 Deva Press, pp.36.

  • The theories of Alfred J Plechner D.V.M. state that low amounts of free adrenal cortisone combined with too much adrenal estrogen and the subsequent binding of thyroid hormones by estrogen from the adrenals can contribute to a wide range of health related problems has support from other experts. The Great Smokies Diagnostic Laboratory (www.gsdl.com) states in their Adrenal Cortex Stress Profile that "Researchers have proposed that CFS is actually a disease of the hypothalamic-pituitary-adrenal axis. Unlike ordinary fatigue, however, CFS is typically characterized by low free cortisol levels and adrenal insufficiency. Raising cortisol levels by even small amounts has been found to improve unexplained fatigue symptoms in many CFS patients."

  • Demitrack MA et al. J Clin Endocrinol Metab 1991; 73: 1224

  • Demitrack, Mark A., Janet K. Dale, Stephen E. Straus et al.; "Evidence for the Impaired Activation of the Hypothalamic-Pituitary-Adrenal Axis in Patients With Chronic Fatigue Syndrome"; Journal of Clinical Endocrinology and Metabolism, December 1991.

  • NEUROENDOCRINE STUDIES IN CHRONIC FATIGUE SYMPTOMS
    Dr Anthony J Cleare, Senior Lecturer in Psychological Medicine, Guy's King's and St Thomas' school of Medicine, London.

  • Cleare AJ. The neuroendocrinology of chronic fatigue syndrome.Endocr Rev.2003; 24:236–52.25.
  • Jason LA, Sorenson M, Porter N, Belkairous N (2010), "An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome", Neuroscience & Medicine, 2011, 2, 14-27, PMID: 21892413
  • Cleare AJ, O'Keane V, Miell J. Plasma leptin in chronic fatigue syndrome and a placebo-controlled study of the effects of low dose hydrocortisone on leptin secretion. Clin Endocrinol (Oxf).2001; 55:113–9
  • McKenzie R, O'Fallon A, Dale J, et al. Low-dose hydrocortisone for treatment of chronic fatigue syndrome : a randomized controlled trial. JAMA.1998;280:1061–6
  • Cleare AJ, Heap E, Malhi G S, et al. Low-dose hydrocortisone in chronic fatigue syndrome : a randomised cross over trial.Lancet.1999;353:455–8

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(b) Abnormal HPA axis (Hypothalmus Pituary Adrenal axis)

  • Evidence for impaired activation of hypothalmic-pituary axis in patients with CFS. Journal of Clinical Endocrinology and Metabolism, 1991, 73, 1224-1234. MA. Demitrack.
  • Hypothalamic–pituitary–adrenal axis dysfunction in chronic fatigue syndrome. Andrew S. Papadopoulos & Anthony J. Cleare. Nature Reviews Endocrinology 8, 22-32 (January 2012)
  • M. Demitrack and L. Crofford, "Evidence For and Pathophysiologic Implications of Hypothalamic-Pituitary -Adrenal Axis Dysregulation in Fibromyalgia and Chronic Fatigue Syndrome," Annals of the New York Academy of Sciences, Vol. 840, 1998, pp. 684-697.
  • Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. Bakheit, AMO., Behan, PO., Dinan, TG., Gray, CE and O'Keane, VO.; British Medical Journal, 1992, 304, 1010-2.
  • L. V. Scott, S. Medbak and T. G. Dinan, "Blunted Adrenocorticotropin and Cortisol Responses to Corticotropin- Releasing Hormone Stimulation in Chronic Fatigue
    Syndrome," Acta Psychiatrica Scandinavica, Vol. 97, 1998, pp. 450-457.
  • Adler GK, Manfredsdottir VF, Rackow RM. 2002 Hypothalamic-pituitary-adrenal axis function in fibromyalgia and chronic fatigue sydrome. The Endocrinologist 12:513-524.

  • Indication of endocrine abnormality induced by dysfunction of 5-HT system in CFS. 5-HT transporter gene polyphormism in CFS patients. Dysfunction in 5-HT system in the animal models. Reduced binding potential of 5-HTT in CFS patients.
    Neuroscience of Fatigue and CFS/ME by Using PET Molecular Imaging and Functional Neuroimaging
    Yasuyoshi Watanabe, Masaski Tanaka, Kei Mizuno, Akira Ishii, Emi Yamano, Sanae Fukuda, Yasuhito Nakatomi, Kouzi Yamaguti, and Hirohiko Kuratsune. IACFS/ME Conference. Translating Science into Clinical Care. March 20-23, 2014 • San Francisco, California, USA

  • Scott LV, Dinan TG: Urinary free cortisol excretion in chronic fatigue syndrome, major depression and in healthy volunteers. J Affect Disord 1998, 47:49-54.
  • Ottenweller JE, Sisto SA, McCarty RC, Natelson BH. 2001 Hormonal responses to exercise in chronic fatigue syndrome. Neuropsychobiology 43:34-41.
  • Clinical spectrum of postviral fatigue syndrome. Behan, PO and Bakheit, AMO; British Medical Bulletin, 1991, 47, 4, 793-808.

  • Torpy DJ. 2001 Neuroendocrinology, genetics and chronic fatigue syndrome. CFS Res Rev 2(4):1-3.

  • Neeck G, Crofford LJ. 2000 Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am 26:989-1002.

  • Contrasting neuroendocrine responses in depression and chronic fatigue syndrome. Cleare, AJ., Bearn, J., Allain, T., McGregor, A., Wessely, S., Murray, RM and O'Keane, V.; Journal of Affective Disorders, 1995, 35, 283-289.

  • Kurup RK, Kurup PA. 2003 Hypothalamic digoxin, cerebral chemical dominance and myalgic encephalomyelitis. Int J Neurosci 113:445-457.
  • Evidence for impaired activation of the hypothalamic- pituitary-adrenal axis in patients with chronic fatigue syndrome. Demitrack, MA, Dale, JK, Straus, SE., Laue, L., Listwalk, SJ., Kruesi, MJP., Chrousos, GP and Gold, PW.; Journal of Clinical Endocrinology and Metabolism, 1991, 73, 1224-1234.

  • Defective dexamethasone induced growth hormone release in chronic fatigue syndrome: evidence for glucocorticoid receptor resistance and lack of plasticity? Majeed, T., Dinan, TG., Thakore, J., Gray, C and Behan, PO.; Journal of the Irish Colleges of Physicians and Surgeons, 1995, 24, 1, 20-24.

  • Disturbance of hypothalamic function and evidence for persistent enteroviral infection in patients with chronic fatigue syndrome. Richardson, J.; Journal of Chronic Fatigue Syndrome, 1995, 1, 2, 59-66.

  • Ur E et al. Eur Arch Psychiatry Clin Neurosci l992; 241: 317

  • Scott LV, Dinan TG. J Affect Disord 1998; 47: 49

  • Scott LV, Medbak S, Dinan TG. The low dose ACTH test in chronic fatigue syndrome and in health. Clin Endocrinol (Oxf).1998; 48:733–7.
  • Crofford LJ, Young EA, Engleberg NC, et al. Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome .Brain Behav Immun. 2004;18:314–25.33.
  • Buskila D, Press J. Neuroendocrine mechanisms in fibromyalgia-chronic fatigue.Best Pract Res Clin Rheumatol.2001; 15:747–58
  • Bakheit AM et al. Acta Neurol Scand l993; 87: 234 "Arginine-vasopressin secretion was found to be erratic in patients with CFS and also total body water content was increased. The investigators suggested that these findings might indicate hypothalamic dysfunction in CFS, perhaps triggered by a persistent viral infection."
  • Bakheit AM et al. BMJ 1992; 304: 1010

  • "Association of Corticosteroid-Binding Globulin Gene Polymorphisms with Chronic Fatigue Syndrome"
    Torpy, et al . Medical University of Queensland, Brisbane (Australia)
    Research findings presented to the 84th Annual Meeting of The Endocrine Society, held on June 19-22, 2001, in San Francisco

  • "Dr Vesselinova has been measuring blood and salivary melatonin levels through the night and found them to be depressed in CFS patients. This is to be expected since we know that hormone output from the hypothalamus/pituitary/adrenal axis is abnormal, so the pineal, a similar gland, is likely to be affected."
    Dr. Sarah Myhill, Wales, UK.  Dr Vesselinova is a doctor at Lister Hospital in London, England.

  • Altered Interrelations among Plasma Stress Hormones during Treadmill Exercise in Females with Chronic Fatigue Syndrome.
    Habib et al. The Clinical Nuroendocrinology Branch of the NIMH in Bethesda, MD, USA
    This project found "significant abnormalities in the interaction between the sympathetic-adrenal limb and the HPA limb of the stress system in CFS". This suggests that the abnormal catecuolamine metabolism could very well contribute to the deficient stress response in ME/CFIDS patients
    Research findings presented to the 84th Annual Meeting of The Endocrine Society, held on June 19-22, 2001, in San Francisco.

  • Thyroid abnormalities in CFS patients.  "in CFS patients the hypothalamic-pituitary-adrenal axis is damaged and not working properly. Therefore one sees a normal or low TSH and depressed T4 in CFS."
    Research by Dr. Sarah Myhill, author of  book "Diagnosing and treating Chronic Fatigue Syndrome",  www.drmyhill.co.uk

  • Alterations in Diurnal Salivary Cortisol Rhythm in a Population-Based Sample of Cases With Chronic Fatigue Syndrome
    Urs M. Nater et al. Psychosomatic Medicine April 2008 vol. 70 no. 3 298-305
  • An article in the Journal of Affective Disorders described a study in which cortisol levels were measured in 10 patients with CFS, 15 patients with major depression, and 25 healthy controls. Baseline circulating cortisol levels were highest in the depressed patients; lowest in the CFS patients; and intermediate between the two in the control group of 25 healthy individuals. Prolactin responses to the selective serotonin-releasing agent d-fenfluramine were lowest in the depressed patients, highest in the CFS patients, and intermediate between both in the healthy group. The authors concluded that depression is associated with hypercortisolemia and reduced central serotonin neurotransmission and suggest that CFS may be associated with hypocortisolemia and increased 5-HT function (Cleare et al. 1995).
  • Abnormal 5 H-T axis and abnormal production of cortisol. (Professor Peter Behan, The Institute of Neurological Sciences, University of Glasgow, Scotland.)

  • Jason LA, Sorenson M, Porter N, Belkairous N (2010), "An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome", Neuroscience & Medicine, 2011, 2, 14-27, PMID: 21892413

  • Dr. Straus, working with researchers at the National Institute of Mental Health and the National Institute of Child Health and Human Development, found that CFS patients have decreased amounts of a hormone called cortisol, which is part of the natural "fight or flight" response. CFS patients also have decreased amounts of the hormone that instructs the brain to produce cortisol, which is called CRH (which is short for "corticotropin releasing hormone").

  • Torpy DJ, Bachmann AW, Grice JE, et al. 2001 Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension. J Clin Endocrinol Metab 86:3692-3700.

  • Torpy DJ, Bachmann AW, Gartside M, et al. 2004 Association between chronic fatigue syndrome and the corticosteroid-binding globulin geen ALA SER224 polymorphism. Endocrine Res 30:417-429.

  • Scott LV, Dinan TG: Urinary free cortisol excretion in chronic fatigue syndrome, major depression and in healthy volunteers. J Affect Disord 1998, 47:49-54.

  • Narita M, Nishigami N, Narita N, et al. 2003 Association between serotonin transported gene polymorphism and chronic fatigue syndrome. Biochem Biophys Res Commun 311:264-266.

  • I. J. Elenkov, R.L. Wilder, G. P. Chrousos and E. S. Vizi, "The Sympathetic Nerve—An Integrative Interface Between Two Supersystems: The Brain and the Immune System," Pharmacological Reviews, Vol. 52, No. 2, 2000, pp. 595-638.
  • B. V. Van Houdenhove, F. Van Den Eede and P. Luyten, "Does Hypothalamic-Pituitary-Adrenal Axis Hypofunction in Chronic Fatigue Syndrome Reflect a 'Crash in the Stress System?" Medical Hypothesis, Vol. 72, No. 6,2009, pp. 701-705. .
  • Straus, Stephen E. et al.; "Lymphocyte Phenotype and Function in the Chronic Fatigue Syndrome"; Journal of Clinical Immunology 13(1):30, 1993.

  • Straus, Stephen E. et al.; "Allergy and the Chronic Fatigue Syndrome"; Journal of Allergy and Clinical Immunology 81:791, May 1988.

 

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