ME and CFS Medical Abnormalities – Endocrine System

 

Following is a list of articles about abnormalities with the endocrine system in ME and CFS.

Links to the more than 1,000 peer-reviewed journal articles are listed on the ME and CFS Medical Abnormalities page of this website.

 

Sedghamiz H, Morris M, Craddock TJA, Whitley D, Broderick G. High-fidelity discrete modeling of the HPA axis: a study of regulatory plasticity in biology. BMC Syst Biol. 2018 Jul 17;12(1):76. PMID: 30016990

The hypothalamic-pituitary-adrenal (HPA) axis is a central regulator of stress response and its dysfunction has been associated with a broad range of complex illnesses including Gulf War Illness (GWI) and Chronic Fatigue Syndrome (CFS). The authors introduce and apply a generalized discrete formalism to recover multiple stable regulatory programs of the HPA axis using little more than connectivity between physiological components.

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Roerink ME, Roerink SHPP, Skoluda N, van der Schaaf ME, Hermus ARMM, van der Meer JWM, Knoop H, Nater UM. Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome. Horm Behav. 2018 Jul;103:1-6. PMID: 29807037

This study confirms the altered dynamics of the HPA axis in a group of CFS patients, and for the first time shows that this might also be present for long-term cortisol measures.

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Ruiz-Núñez B, Tarasse R, Vogelaar EF, Janneke Dijck-Brouwer DA, Muskiet FAJ. Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case-Control Study. Front Endocrinol (Lausanne). 2018 Mar 20;9:97. PMID: 29615976

CFS patients exhibited similar thyrotropin, but lower free triiodothyronine (FT3), total thyroxine (TT4), total triiodothyronine (TT3), %TT3, sum activity of deiodinases, secretory capacity of the thyroid gland, 24-h urinary iodine, and higher % reverse T3 (rT3). FT3 below the reference range, consistent with the “low T3 syndrome,” was found in 16/98 CFS patients vs. 7/99 controls.

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Vangeel EB, Kempke S, Bakusic J, Godderis L, Luyten P, Van Heddegem L, Compernolle V, Persoons P, Lambrechts D, Izzi B, Freson K, Claes S. Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients. J Psychosom Res. 2018 Jan;104:55-60. PMID: 29275786

Although the precise mechanisms are not yet understood, previous studies have suggested that chronic fatigue syndrome (CFS) is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and trauma in early childhood. This study replicated findings of NR3C1-1F DNA hypomethylation in CFS patients versus controls. Our results support the hypothesis of HPA axis dysregulation and enhanced glutocoricoid sensitivity in CFS.

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Tomic S, Brkic S, Lendak D, Maric D, Medic Stojanoska M, Novakov Mikic A. Neuroendocrine disorder in chronic fatigue syndrome. Turk J Med Sci. 2017 Aug 23;47(4):1097-1103. PMID: 29154201

The aim of this study was to determine the function of the hypothalamic-pituitary-adrenal axis (HPA) and thyroid function in women of reproductive age suffering from CFS. Cortisol serum levels were normal in both groups. The distinctively positive moderate correlation of morning and afternoon cortisol levels that was observed in healthy women was absent in the CFS group. This may indicate a disturbed physiological rhythm of cortisol secretion. Although basal serum T4, T3, and TSH levels were normal in all subjects, concentrations of T3 were significantly lower in the CFS group.

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Milrad SF, Hall DL, Jutagir DR, Lattie EG, Czaja SJ, Perdomo DM, Fletcher MA, Klimas N, Antoni MH. Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model. Int J Psychophysiol. 2017 Sep 14. PMID: 28918107

Since depression is known to be associated with HPA axis dysfunction and greater inflammation, a psychoneuroendocrinological (PNE) model of inflammation was examined in persons diagnosed with CFS in order to uncover underlying biopsychosocial mechanisms in this poorly understood chronic illness. Results highlight the role of depression, cortisol and inflammation in possible biological mechanisms involved in the pathophysiology of CFS.

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Vangeel E, Van Den Eede F, Hompes T, Izzi B, Del Favero J, Moorkens G, Lambrechts D, Freson K, Claes S. Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With HPA Axis Hypofunction and Childhood Trauma. Psychosom Med. 2015 Oct;77(8):853-62. PMID: 26230484

The authors found evidence of NR3C1 promoter hypomethylation in female patients with CFS. The functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (GR hypersuppression).

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Hall DL, Lattie EG, Antoni MH, Fletcher MA, Czaja S, Perdomo D, Klimas NG. Stress management skills, cortisol awakening response, and post-exertional malaise in Chronic Fatigue Syndrome. Psychoneuroendocrinology. 2014 Nov;49:26-31. PMID: 25049069

In a population of CFS patients, greater perceived stress management skills related to greater cortisol awakening response and greater cortisol awakening response related to less post-exertional malaise severity.

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Craddock TJ, Fritsch P, Rice MA Jr, del Rosario RM, Miller DB, Fletcher MA, Klimas NG, Broderick G. A role for homeostatic drive in the perpetuation of complex chronic illness: Gulf War Illness and chronic fatigue syndrome. PLoS One. 2014 Jan 8;9(1):e84839. PMID: 24416298

In female CFS subjects, expression of endocrine-immune markers aligned with an alternate homeostatic state displaying hypocortisolism, high estradiol, and a shift towards an anti-inflammatory Th2 activation. These results support a role for homeostatic drive in perpetuating dysfunctional cortisol levels through persistent interaction with the immune system and HPG axis.

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Nijhof SL1, Rutten JM2, Uiterwaal CS3, Bleijenberg G4, Kimpen JL5, Putte EM6. The role of hypocortisolism in chronic fatigue syndrome. Psychoneuroendocrinology. 2014 Apr;42:199-206. PMID: 24636516

Pre-treatment salivary cortisol levels were significantly lower in CFS patients than in healthy controls. The hypocortisolism found in CFS patients was significantly correlated to the amount of sleep.

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Powell DJ, Liossi C, Moss-Morris R, Schlotz W. Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: A systematic review and subset meta-analysis. Psychoneuroendocrinology. 2013 Nov;38(11):2405-22. PMID: 23916911

Meta-analyses revealed an attenuation of the cortisol-awakening response increase within CFS compared to controls but no statistically significant differences between groups for other markers.

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Aschbacher K, Adam EK, Crofford LJ, Kemeny ME, Demitrack MA, Ben-Zvi A. Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study. Brain Behav Immun. 2012 Oct;26(7):1047-56. PMID: 22687333

A dynamic systems model was used to generate parameters describing a phenotype of Hypothalamic-Pituitary-Adrenal (HPA) behavior in a sample of 36 patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) and 36 case-matched healthy controls.

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Papadopoulos AS, Cleare AJ. Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev Endocrinol. 2011 Sep 27. PMID: 21946893

The weight of current evidence supports the presence of the following factors related to hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with chronic fatigue syndrome (CFS): mild hypocortisolism; attenuated diurnal variation of cortisol; enhanced negative feedback to the HPA axis; and blunted HPA axis responsiveness.

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Ursini F, Succurro E, Grembiale A, Gagliardi DA, Arturi F. The HPA axis in the pathogenesis of chronic fatigue syndrome. Clin Ter. 2010 Sep-Oct;161(5):461-4. PMID: 20949245

A review of evidence about a role of hypothalamic-pituitary-adrenal axis in the pathogenesis of CFS.

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Shishioh-Ikejima N, Ogawa T, Yamaguti K, Watanabe Y, Kuratsune H, Kiyama H. The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients. BMC Neurol. 2010 Aug 23;10:73. PMID: 20731841

CFS patients with a disease duration of <or= 5 years had significantly higher levels of alpha-MSH in their peripheral blood, and this has potential as a biomarker.

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Wyller VB, Evang JA, Godang K, Solhjell KK, Bollerslev J. Hormonal alterations in adolescent chronic fatigue syndrome. Acta Paediatr. 2010 May;99(5):770-3. PMID:20199497

Among CFS patients, plasma antidiuretic hormone was significantly decreased and serum osmolality and plasma renin activity were significantly increased (p < or = 0.001). Serum concentration of aldosterone, cortisol, NT-proBNP and sex hormones were not significantly different in the two groups.

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Fomicheva EE, Filatenkova TA, Rybakina EG. Activity in the hypothalamo-hypophyseal-adrenocortical system on experimental induction of chronic fatigue syndrome. Neurosci Behav Physiol. 2010 Mar;40(3):245-50. PMID: 20146018

In an experimental model, CFS was associated with abnormalities in adrenal function.

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Weaver SA, Janal MN, Aktan N, Ottenweller JE, Natelson BH. Sex differences in plasma prolactin response to tryptophan in chronic fatigue syndrome patients with and without comorbid fibromyalgia. J Womens Health (Larchmt). 2010 May;19(5):951-8. PMID: 20384451

Women with CFS alone, but not CFS plus fibromylgia, showed upregulated plasma prolactin responses compared with controls. There were no differences among groups of men.

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Evans KM, Flanagan DE, Wilkin TJ. Chronic fatigue: is it endocrinology? Clin Med. 2009 Feb;9(1):34-8. PMID: 19271598

CFS patients’ presenting symptoms are not early features of “significant endocrine pathology.”

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Rybakina EG, Shanin SN, Fomicheva EE, Korneva EA. Cellular and molecular mechanisms of interaction between the neuroendocrine and immune systems under chronic fatigue syndrome in experiment. Ross Fiziol Zh Im I M Sechenova. 2009 Dec;95(12):1324-35. PMID: 20141043

In an experimental model, CFS was associated with alterations in HPA axis activity.  This  likely results in changes in both the activity of immune-competent cells and membranes of brain cells.

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Fomicheva EE, Filatenkova TA, Rybakina EG. Activity of hypotnalamic-pituitary-adrenal axis by induction of experimental chronic fatigue syndrome. Ross Fiziol Zh Im I M Sechenova. 2009 Jan;95(1):11-8. PMID: 19323439

CFS patients display disordered HPA axis and adrenal functioning.

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Van Houdenhove B, Van Den Eede F, Luyten P. Does hypothalamic-pituitary-adrenal axis hypofunction in chronic fatigue syndrome reflect a ‘crash’ in the stress system? Med Hypotheses. 2009 Jun;72(6):701-5. PMID: 19237251

The authors hypothesize that that HPA axis hypofunction in CFS, conceptualized within a system-biological perspective, primarily reflects a fundamental and persistent dysregulation of the neurobiological stress system.

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Veldman J, Van Houdenhove B, Verguts J. Chronic fatigue syndrome: a hormonal origin? A rare case of dysmenorrhea membranacea. Arch Gynecol Obstet. 2009 May;279(5):717-20. PMID: 18787800

A case study of involving membranous dysmenorrhea suggests a hormonal dysfunction as a possible cause of CFS.

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Papadopoulos A, Ebrecht M, Roberts AD, Poon L, Rohleder N, Cleare AJ. Glucocorticoid receptor mediated negative feedback in chronic fatigue syndrome using the low dose (0.5 mg) dexamethasone suppression test. J Affect Disord. 2009 Jan;112(1-3):289-94. PMID: 18573538

A low-dose dexamethasone (0.5 mg) suppression test in CFS patients showed no differences with controls except in the patients who also were depressed.

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Fuite J, Vernon SD, Broderick G. Neuroendocrine and immune network re-modeling in chronic fatigue syndrome: an exploratory analysis. Genomics. 2008 Dec;92(6):393-9. PMID: 18775774

This work investigates the significance of changes in association patterns linking indicators of neuroendocrine and immune activity in patients with CFS. Findings align with known mechanisms of chronic inflammation and support possible immune-mediated loss of thyroid function in CFS exacerbated by blunted HPA axis responsiveness.

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Torres-Harding S, Sorenson M, Jason L, Maher K, Fletcher MA, Reynolds N, Brown M. The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome. J Appl Biobehav Res. 2008 Jan 1;13:157-180. PMID: 19701493

CFS patients show deviations from expected patterns of cortisol, and this appears to be associated with fatigue and pain.

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Nater UM, Maloney E, Boneva RS, Gurbaxani BM, Lin JM, Jones JF, Reeves WC, Heim C. Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls. J Clin Endocrinol Metab. 2008 Mar;93(3):703-9. PMID: 18160468

CFS was associated with an attenuated morning cortisol response, but the effect was limited to women.

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Van Den Eede F, Moorkens G, Hulstijn W, Van Houdenhove B, Cosyns P, Sabbe BG, Claes SJ. Combined dexamethasone/corticotropin-releasing factor test in chronic fatigue syndrome. Psychol Med. 2008 Jul;38(7):963-73. PMID: 17803834

CFS is globally associated with reduced cortisol responses in the combined low-dose Dex/CRF test, but this effect is only clearly present in CFS patients without a history of early-life stress.

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Van Den Eede F, Moorkens G, Van Houdenhove B, Cosyns P, Claes SJ. Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. Neuropsychobiology. 2007;55(2):112-20. PMID: 17596739

Hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis is a problem in a proportion of the patients with CFS, possibly as a consequence of other factors.

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Jerjes WK, Taylor NF, Wood PJ, Cleare AJ. Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome. Psychoneuroendocrinology. 2007 Feb;32(2):192-8. PMID: 17276605

There is enhanced sensitivity of the HPA axis to negative feedback in CFS.

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Gräns H, Nilsson M, Dahlman-Wright K, Evengård B. Reduced levels of oestrogen receptor beta mRNA in Swedish patients with chronic fatigue syndrome. J Clin Pathol. 2007 Feb;60(2):195-8. PMID: 16731592

The CFS group showed significantly lower mRNA expression levels of ERbeta wt compared with the healthy control group. This is consistent with an immune-mediated pathogenesis of CFS. A possible connection between oestrogen, oestrogen receptors and CFS should be evaluated further.

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Tanriverdi F, Karaca Z, Unluhizarci K, Kelestimur F. The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome. Stress. 2007 Mar;10(1):13-25. PMID: 17454963

The role of the hypothalamo-pituitary-adrenal (HPA) axis in CFS is discussed.

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Maloney EM, Gurbaxani BM, Jones JF, de Souza Coelho L, Pennachin C, Goertzel BN. Chronic fatigue syndrome and high allostatic load. Pharmacogenomics. 2006 Apr;7(3):467-73. PMID: 16610956

CFS was associated with a high level of allostatic load. The three allostatic load components that best discriminated cases from controls were waist:hip ratio, aldosterone and urinary cortisol.

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Maes M, Mihaylova I, De Ruyter M. Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS. Neuro Endocrinol Lett. 2005 Oct;26(5):487-92. PMID: 16264414

CFS is accompanied by lowered levels of DHEAS, and this may play a role in the immune (defect in the early activation of T cells) and the inflammatory pathophysiology of CFS.

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Segal TY, Hindmarsh PC, Viner RM. Disturbed adrenal function in adolescents with chronic fatigue syndrome. J Pediatr Endocrinol Metab. 2005 Mar;18(3):295-301. PMID: 15813608

Adolescents with CFS have subtle alterations in adrenal function suggesting a reduction in central stimulation of the adrenal glands.

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Di Giorgio A, Hudson M, Jerjes W, Cleare AJ. 24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome. Psychosom Med. 2005 May-Jun;67(3):433-40. PMID: 15911907

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 evidence of subtle dysregulation of the HPA axis in CFS.

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Crofford LJ, Young EA, Engleberg NC, Korszun A, Brucksch CB, McClure LA, Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome. Brain Behav Immun. 2004 Jul;18(4):314-25. PMID: 15157948

CFS patients, fibromyalgia patients and normal controls all look different in their basal circadian architecture of HPA axis hormones.

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Cevik R, Gur A, Acar S, Nas K, Sarac AJ. 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. BMC Musculoskelet Disord. 2004 Dec 8;5:47. PMID: 15588275

There were no significant differences in FSH, LH, estradiol and progesterone levels in both of menstrual phases of CFS patients versus controls. Cortisol levels were significantly lower in patients compared to controls.

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Gaab J, Engert V, Heitz V, Schad T, Schürmeyer TH, Ehlert U. Associations between neuroendocrine responses to the Insulin Tolerance Test and patient characteristics in chronic fatigue syndrome. J Psychosom Res. 2004 Apr;56(4):419-24. PMID: 15094026

CFS patients had a significantly reduced area under the ACTH response curve (AUC) in the ITT. The AUC was significantly associated with the duration of CFS symptoms and the severity of fatigue symptomatology. In addition, duration of CFS was correlated with the severity of fatigue symptoms.

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Zarković M, Pavlović M, Pokrajac-Simeunović A, Cirić J, Beleslin B, Penezić Z, Ognjanović S, Savić S, Poluga J, Trbojević B, Drezgić M. Disorder of adrenal gland function in chronic fatigue syndrome. Srp Arh Celok Lek. 2003 Sep-Oct;131(9-10) 370-4. PMID: 15058215

Regarding the adrenal response to ACTH stimulation CFS subjects present heterogeneous group. In some subjects cortisol response is preserved, while in the others it is similar to one found in secondary adrenal insufficiency.

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Murphy BE, Abbott FV, Allison CM, Watts C, Ghadirian AM. Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome. Psychoneuroendocrinology. 2004 Feb;29(2):245-68. PMID: 14604604

Increases in ring A-reduced progesterone metabolites, particularly isopregnanolone, are associated with CFS. The pathophysiology of CFS is unlikely to be due to depression.

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Gaab J, Hüster D, Peisen R, Engert V, Heitz V, Schad T, Schürmeyer T, Ehlert U. Assessment of cortisol response with low-dose and high-dose ACTH in patients with chronic fatigue syndrome and healthy comparison subjects. Psychosomatics. 2003 Mar-Apr;44(2):113-9. PMID: 12618533

No response differences for salivary and plasma cortisol were detectable after administration of either low-dose or high-dose ACTH for CFS patients vs. controls, indicating that primary adrenal insufficiency is unlikely to play a significant role in the etiology of chronic fatigue syndrome.

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Gaab J, Hüster D, Peisen R, Engert V, Heitz V, Schad T, Schürmeyer TH, Ehlert U. Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation. Psychosom Med. 2002 Nov-Dec;64(6):951-62. PMID: 12461200

CFS patients seem capable of mounting a sufficient cortisol response under different types of stress, but on a central level subtle dysregulations of the HPA axis exist.

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Racciatti D, Guagnano MT, Vecchiet J, De Remigis PL, Pizzigallo E, Della Vecchia R, Di Sciascio T, Merlitti D, Sensi S.Chronic fatigue syndrome: circadian rhythm and hypothalamic-pituitary-adrenal (HPA) axis impairment. Int J Immunopathol Pharmacol. 2001 Jan-Apr;14(1):11-15. PMID: 12622884

The circadian rhythms of prolactin, thyrotropic hormone, adrenocorticotropic hormone and cortisol were statistically significant in both CFS and control groups.

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van Rensburg SJ, Potocnik FC, Kiss T, Hugo F, van Zijl P, Mansvelt E, Carstens ME, Theodorou P, Hurly PR, Emsley RA, Taljaard JJ. Serum concentrations of some metals and steroids in patients with chronic fatigue syndrome with reference to neurological and cognitive abnormalities. Brain Res Bull. 2001 May 15;55(2):319-25. PMID: 11470334

CFS patients had significantly increased serum aluminum and decreased iron compared to controls. In the females, serum iron and dehydroepiandrosterone sulphate were significantly decreased and correlated. Total cholesterol was significantly increased, and significantly negatively correlated with dehydroepiandrosterone sulphate. There were no differences in zinc, copper, cortisol, hemoglobin, transferrin and ferritin concentrations, or in transferrin genetic subtypes.

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Vassallo CM, Feldman E, Peto T, Castell L, Sharpley AL, Cowen PJ. Decreased tryptophan availability but normal post-synaptic 5-HT2c receptor sensitivity in chronic fatigue syndrome. Psychol Med. 2001 May;31(4):585-91. PMID: 11352361

Chronic fatigue syndrome (CFS) has been associated with increased prolactin (PRL) responses to the serotonin (5-HT) releasing agent fenfluramine. The sensitivity of post-synaptic 5-HT2c receptors was not increased in patients with CFS. This suggests that the increased PRL response to fenfluramine in CFS is due to elevated activity of pre-synaptic 5-HT neurones.

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Visser J, Lentjes E, Haspels I, Graffelman W, Blauw B, de Kloet R, Nagelkerken L. Increased sensitivity to glucocorticoids in peripheral blood mononuclear cells of chronic fatigue syndrome patients, without evidence for altered density or affinity of glucocorticoid receptors. J Investig Med. 2001 Mar;49(2):195-204. PMID: 11288761

Peripheral blood mononuclear cells of CFS patients display an increased sensitivity to glucocorticoids.

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Cleare AJ, Blair D, Chambers S, Wessely S. Urinary free cortisol in chronic fatigue syndrome. Am J Psychiatry. 2001 Apr;158(4):641-3. PMID: 11282703

There is mild hypocortisolism in chronic fatigue syndrome.

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Visser JT, De Kloet ER, Nagelkerken L. Altered glucocorticoid regulation of the immune response in the chronic fatigue syndrome. Ann N Y Acad Sci. 2000;917:868-75. PMID: 11268418

In CFS patients a decreased Th1/Th2 balance may be the result of selective effects of glucocortiocoids on the IL-10/IL-12 regulatory circuit.

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Ottenweller JE, Sisto SA, McCarty RC, Natelson BH. Hormonal responses to exercise in chronic fatigue syndrome. Neuropsychobiology. 2001 Jan;43(1):34-41. PMID: 11150897

The authors looked at endocrine measures in CFS patients before and after an exercise challenge, and conclude that post-exertional malaise is not the result of endocrine problems.

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Torpy DJ, Bachmann AW, Grice JE, Fitzgerald SP, Phillips PJ, Whitworth JA, Jackson RV. Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension.J Clin Endocrinol Metab. 2001 Aug;86(8):3692-700. PMID: 11502797

The authors describe a 39-member Italian-Australian family with a novel complete loss of function (null) mutation of the corticosteroid-binding globulin gene. Idiopathic chronic fatigue was present in 12 of 14 adult null heterozygote subjects (86%) and in 2 of 3 null homozygotes. Five cases met the Centers for Disease Control criteria for chronic fatigue syndrome.

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Altemus M, Dale JK, Michelson D, Demitrack MA, Gold PW, Straus SE. Abnormalities in response to vasopressin infusion in chronic fatigue syndrome. Psychoneuroendocrinology. 2001 Feb;26(2):175-88. PMID: 11087963

Patients with chronic fatigue syndrome had a reduced ACTH response to a vasopressin infusion and a more rapid cortisol response to the infusion.

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Scott LV, Svec F, Dinan T. A preliminary study of dehydroepiandrosterone response to low-dose ACTH in chronic fatigue syndrome and in healthy subjects. Psychiatry Res. 2000 Dec 4;97(1):21-8. PMID: 11104854

ACTH significantly elevates DHEA levels, with no difference in output between CFS and healthy subjects. The DHEA/cortisol ratio decreased in response to ACTH stimulation in healthy subjects but not in the CFS cohort. We suggest this divergence of response between the two groups represents an imbalance in the relative synthetic pathways of the CFS group which, if present chronically and if comparable to daily stressors, may manifest itself as an inappropriate response to stress.

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Starr A, Scalise A, Gordon R, Michalewski HJ, Caramia MD. Motor cortex excitability in chronic fatigue syndrome. Clin Neurophysiol. 2000 Nov;111(11):2025-31. PMID: 11068238

Individuals with CFS do not show the normal fluctuations of motor cortical excitability that accompany and follow non-fatiguing repetitive bimanual finger movements.

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Knook L, Kavelaars A, Sinnema G, Kuis W, Heijnen CJ. High nocturnal melatonin in adolescents with chronic fatigue syndrome. J Clin Endocrinol Metab. 2000 Oct;85(10):3690-2. PMID: 11061525

Nocturnal saliva melatonin levels were significantly higher in CFS patients, compared with controls, at midnight, 0100 h, and 0200 h (P < 0.001).

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Berwaerts J, Moorkens G, Abs R. Secretion of growth hormone in patients with chronic fatigue syndrome. Growth Horm IGF Res. 1998 Apr;8 Suppl B:127-9. PMID: 10990147

CFS patients have a tendency for impaired spontaneous nocturnal GH secretion.

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Moorkens G, Berwaerts J, Wynants H, Abs R. Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome. Clin Endocrinol (Oxf). 2000 Jul;53(1):99-106. PMID: 10931086

There was a significant impairment of GH response during insulin-induced hypoglycaemia and a low nocturnal GH secretion in CFS patients. These changes did, however, not lead to different concentrations in serum IGF-I. Significantly increased prolactin and TSH levels were found when compared to controls.

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Scott LV, Teh J, Reznek R, Martin A, Sohaib A, Dinan TG. Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study. Psychoneuroendocrinology. 1999 Oct;24(7):759-68. PMID: 10451910

Adrenal gland size was reduced by over 50% in CFS patients, indicative of significant adrenal atrophy.

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Scott LV, Salahuddin F, Cooney J, Svec F, Dinan TG. Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health. J Affect Disord. 1999 Jul;54(1-2):129-37. PMID: 10403156

DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group. A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS, is suggested.

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Scott LV, Medbak S, Dinan TG. Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers. Biol Psychiatry. 1999 Jun 1;45(11):1447-54. PMID: 10356627

Desmopressin was capable of normalizing the pituitary-adrenal response to corticotropin-releasing hormone in in CFS patients; this suggests there may be increased vasopressinergic responsivity of the anterior pituitary in CFS and/or that desmopressin may be exerting an effect at an adrenal level.

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De Becker P, De Meirleir K, Joos E, Campine I, Van Steenberge E, Smitz J, Velkeniers B. Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome. Horm Metab Res. 1999 Jan;31(1):18-21. PMID: 10077344

CFS patients in this study had normal basal DHEA levels, but a blunted serum DHEA response curve to i.v. ACTH injection.

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Kuratsune H, Yamaguti K, Sawada M, Kodate S, Machii T, Kanakura Y, Kitani T. Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome. Int J Mol Med. 1998 Jan;1(1):143-6. PMID: 9852212

The majority of Japanese patients with CFS had a serum dehydroepiandrosterone sulfate (DHEA-S) deficiency, possibly related to phenomena such as memory, stress, anxiety, sleep and depression.

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Scott LV, Medbak S, Dinan TG. The low dose ACTH test in chronic fatigue syndrome and in health. Clin Endocrinol (Oxf). 1998 Jun;48(6):733-7. PMID: 9713562

This study provides evidence for a subtle pituitary-adrenal insufficiency in subjects with chronic fatigue syndrome compared to healthy volunteers.

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Cannon JG, Angel JB, Abad LW, O’Grady J, Lundgren N, Fagioli L, Komaroff AL. Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. J Clin Immunol. 1998 Jul;18(4):291-8. PMID: 9710746

The results of this study suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.

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Peroutka SJ. Chronic fatigue disorders: an inappropriate response to arginine vasopressin? Med Hypotheses. 1998 Jun;50(6):521-3. PMID: 9710328

Altered water metabolism resulting from inappropriate release and/or response to arginine vasopressin (AVP) is proposed as a pathophysiological basis of certain chronic fatigue disorders.

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Scott LV, Medbak S, Dinan TG. Blunted adrenocorticotropin and cortisol responses to corticotropin-releasing hormone stimulation in chronic fatigue syndrome. Acta Psychiatr Scand. 1998 Jun;97(6):450-7. PMID: 9669518

The release of ACTH was significantly attenuated in a group of CFS patients (P < 0.005), as was the release of cortisol.

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Demitrack MA, Crofford LJ. Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann N Y Acad Sci. 1998 May 1;840:684-97. PMID: 9629295

The authors studied the detailed, pulsatile characteristics of the HPA axis in a group of CFS patients. Results were consistent with the view that patients with CFS have a reduction of HPA axis activity due, in part, to impaired central nervous system drive.

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Scott LV, Burnett F, Medbak S, Dinan TG. Naloxone-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome. Psychol Med. 1998 Mar;28(2):285-93. PMID: 9572086

The release of ACTH (but not cortisol) was significantly blunted in the CFS subjects compared with controls.

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Dinan TG, Majeed T, Lavelle E, Scott LV, Berti C, Behan P. Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome. Psychoneuroendocrinology. 1997 May;22(4):261-7. PMID: 9226729

Release of ACTH (but not cortisol) in response to ipsapirone challenge was significantly blunted in patients with CFS. The authors conclude that serotonergic activation of the hypothalamic-pituitary-adrenal axis is defective in CFS.

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Cannon JG, Angel JB, Abad LW, Vannier E, Mileno MD, Fagioli L, Wolff SM, Komaroff AL. Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome. J Clin Immunol. 1997 May;17(3):253-61. PMID: 9168406

IL-1Ra secretion for CFS patients was twofold higher than controls during the follicular phase, but luteal-phase levels were similar between groups. In both phases of the menstrual cycle, IL-1sRII release was significantly higher for CFS patients compared to controls. These results suggest that an abnormality exists in IL-1 beta secretion in CFS patients that may be related to altered sensitivity to estradiol and progesterone. The increased release of IL-1Ra and sIL-1RII by cells from CFS patients is consistent with the hypothesis that CFS is associated with chronic, low-level activation of the immune system.

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Allain TJ, Bearn JA, Coskeran P, Jones J, Checkley A, Butler J, Wessely S, Miell JP. Changes in growth hormone, insulin, insulinlike growth factors (IGFs), and IGF-binding protein-1 in chronic fatigue syndrome. Biol Psychiatry. 1997 Mar 1;41(5):567-73. PMID: 9046989

In CFS patients, the authors found attenuated basal levels of IGF-I and IGF-II; reduced GH response to hypoglycemia; higher insulin levels; and lower IGFBP-1 levels.

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Sharpe M, Clements A, Hawton K, Young AH, Sargent P, Cowen PJ. Increased prolactin response to buspirone in chronic fatigue syndrome. J Affect Disord. 1996 Nov 4;41(1):71-6. PMID: 8938208

Patients with CFS had significantly higher plasma prolactin concentrations and experienced more nausea in response to buspirone than did controls.

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Bearn J, Allain T, Coskeran P, Munro N, Butler J, McGregor A, Wessely S. Neuroendocrine responses to d-fenfluramine and insulin-induced hypoglycemia in chronic fatigue syndrome. Biol Psychiatry. 1995 Feb 15;37(4):245-52. PMID: 7711161

In a group of CFS patients, the researchers found attenuated prolactin responses to hypoglycemia, a greater ACTH response and higher peak ACTH concentrations.

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Jefferies WM. Mild adrenocortical deficiency, chronic allergies, autoimmune disorders and the chronic fatigue syndrome: a continuation of the cortisone story. Med Hypotheses. 1994 Mar;42(3):183-9. PMID: 8057974

The author hypothesizes that CFS may be related to mild adrenocorticoid deficiency.

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Bakheit AM, Behan PO, Watson WS, Morton JJ. Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome. Acta Neurol Scand. 1993 Mar;87(3):234-8. PMID: 8475696

Patients with post viral fatigue syndrome had significantly low baseline arginine-vasopressin levels and evidence of increased total body water content, suggesting hypothalmic dysfunction.

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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 Dec;73(6):1224-34. PMID: 1659582

CFS patients demonstrated significantly reduced basal evening glucocorticoid levels  and low 24-h urinary free cortisol excretion, but elevated basal evening ACTH concentrations. There was increased adrenocortical sensitivity to ACTH, but a reduced maximal response. Patients showed attenuated net integrated ACTH responses to oCRH.

 

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