Tag: dexamethasone

Glucocorticoid receptor mediated negative feedback in chronic fatigue syndrome using the low dose (0.5 mg) dexamethasone suppression test

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is associated with hypocortisolism, but it is not yet clear the extent to which enhanced negative feedback may underlie this finding.

METHODS: We undertook a low-dose dexamethasone (0.5 mg) suppression test in 18 CFS patients and 20 matched, healthy controls. We measured salivary cortisol levels at 0800 h, 1200 h, 1600 h and 2000 h before and after the administration of 0.5 mg of dexamethasone.

RESULTS: Basal cortisol output was raised in this group of CFS patients compared to controls. Overall, the percentage suppression following dexamethasone administration was no different between CFS (mean+/-sem: 80.4+/-4.4%) and controls (76.2+/-4.9 %). However, the sub-group of patients with CFS and comorbid depression (n=9) showed a significant hypersuppression of salivary cortisol in response to dexamethasone (89.0+/-1.9%; p<0.05 v controls).

LIMITATIONS: The sub-group analysis was on small numbers and should be considered preliminary. Dexamethasone probes only glucocorticoid medicated negative feedback but does not probe mineralocorticoid feedback, the other main physiological feedback mechanism.

CONCLUSION: We found partial support for the hypothesis of enhanced negative feedback in CFS but only in patients with comorbid depression and also in the context of a sample of patients with elevated basal cortisol levels, which is an atypical finding in the literature.

 

Source: 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. doi: 10.1016/j.jad.2008.05.001. Epub 2008 Jun 24. https://www.ncbi.nlm.nih.gov/pubmed/18573538

 

Combined dexamethasone/corticotropin-releasing factor test in chronic fatigue syndrome

Abstract:

BACKGROUND: Studies of hypothalamic-pituitary-adrenal (HPA) axis function in chronic fatigue syndrome (CFS) point to hypofunction, although there are negative reports. Suggested mechanisms include a reduced hypothalamic or supra-hypothalamic stimulus to the HPA axis and enhanced sensitivity to the negative feedback of glucocorticoids. The aim of the current study was to investigate HPA axis function in CFS with the dexamethasone/corticotropin-releasing factor (Dex/CRF) test, in analogy with research in affective disorders.

METHOD: Thirty-four well-characterized female CFS patients and 25 healthy control subjects participated in the low-dose Dex/CRF test. Current major depressive episode was an exclusion criterion. History of early-life stress (ELS) was assessed with the Structured Trauma Interview.

RESULTS: Salivary cortisol responses after 0.5 mg Dex were lower in CFS patients than in controls (before 100 microg CRF, p=0.038; after 100 microg CRF, p=0.015). A secondary analysis revealed an influence of early-life stress and of oestrogen intake. After removal of the 10 participants who were taking an oral oestrogen, patients without a history of ELS showed lower cortisol responses than patients with ELS and controls (before CRF, p=0.005; after CRF, p=0.008).

CONCLUSIONS: 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 ELS. This study provides further support for an enhanced glucocorticoid negative feedback and/or a reduced central HPA axis drive in CFS. Furthermore, it demonstrates that ELS is an important variable to consider in CFS research.

 

Source: 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. Epub 2007 Sep 6. https://www.ncbi.nlm.nih.gov/pubmed/17803834

 

Low-dose dexamethasone suppression test in chronic fatigue syndrome and health

Abstract:

OBJECTIVE: Subtle dysregulations of the hypothalamus-pituitary-adrenal axis in chronic fatigue syndrome have been described. The aim of this study was to examine the negative feedback regulations of the hypothalamus-pituitary-adrenal axis in chronic fatigue syndrome.

METHODS: In 21 patients with chronic fatigue syndrome and 21 healthy control subjects, awakening

and circadian salivary free cortisol profiles were assessed over 2 consecutive days and compared with awakening and circadian salivary free cortisol profiles after administration of 0.5 mg of dexamethasone at 11:00 PM the previous day.

RESULTS: Patients with chronic fatigue syndrome had normal salivary free cortisol profiles but showed enhanced and prolonged suppression of salivary free cortisol after the administration of 0.5 mg of dexamethasone in comparison to the control subjects.

CONCLUSIONS: Enhanced negative feedback of the hypothalamus-pituitary-adrenal axis could be a plausible explanation for the previously described alterations in hypothalamus-pituitary-adrenal axis functioning in chronic fatigue syndrome. Because similar changes have been described in stress-related disorders, a putative role of stress in the pathogenesis of the enhanced feedback is possible.

 

Source: Gaab J, Hüster D, Peisen R, Engert V, Schad T, Schürmeyer TH, Ehlert U. Low-dose dexamethasone suppression test in chronic fatigue syndrome and health. Psychosom Med. 2002 Mar-Apr;64(2):311-8. http://www.ncbi.nlm.nih.gov/pubmed/11914448

 

LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone

Abstract:

Several causes have been held responsible for the chronic fatigue syndrome (CFS), including an altered hypothalamus-pituitary-adrenal gland (HPA)-axis activity, viral infections and a reduced Th1 activity. Therefore, it was investigated whether the regulation of IL-10 is different in CFS.

LPS-induced cytokine secretion in whole blood cultures showed a significant increase in IL-10 and a trend towards a decrease in IL-12 as compared with healthy controls. In patients and controls, IL-12 secretion was equally sensitive to suppression by dexamethasone, whereas IL-10 secretion appeared more sensitive in CFS-patients. In controls, IL-10 and IL-12 secretion were inversely correlated with free serum cortisol (r=-0.492, p<0.02 and r=-0.434, p<0.05, respectively). In CFS, such an inverse correlation was found for IL-12 (r=-0.611, p<0.02) but not for IL-10 (r=-0.341, ns).

These data are suggestive for a disturbed glucocorticoid regulation of IL-10 in CFS.

 

Source: Visser J, Graffelman W, Blauw B, Haspels I, Lentjes E, de Kloet ER, Nagelkerken L. LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone. J Neuroimmunol. 2001 Oct 1;119(2):343-9. http://www.ncbi.nlm.nih.gov/pubmed/11585638

 

Disturbed neuroendocrine-immune interactions in chronic fatigue syndrome

Abstract:

The present study was designed to investigate the interaction between neuroendocrine mediators and the immune system in chronic fatigue syndrome (CFS). We examined the sensitivity of the immune system to the glucocorticoid agonist dexamethasone and the beta2-adrenergic agonist terbutaline in 15 adolescent girls with CFS and 14 age- and sex-matched controls.

Dexamethasone inhibits T-cell proliferation in healthy controls and in CFS patients. However, the maximal effect of dexamethasone on T-cell proliferation is significantly reduced in CFS patients as compared with controls. The beta2-adrenergic receptor agonist terbutaline inhibits tumor necrosis factor-alpha production and enhances interleukin-10 production by monocytes. Our data demonstrate that the capacity of a beta2-adrenergic agonist to regulate the production of these two cytokines is also reduced in CFS patients.

We did not observe differences in baseline or CRH-induced cortisol and ACTH between CFS patients and controls. Baseline noradrenaline was similar in CFS and controls, whereas baseline adrenaline levels were significantly higher in CFS patients. We conclude that CFS is accompanied by a relative resistance of the immune system to regulation by the neuroendocrine system. Based on these data, we suggest CFS should be viewed as a disease of deficient neuroendocrine-immune communication.

 

Source: Kavelaars A, Kuis W, Knook L, Sinnema G, Heijnen CJ. Disturbed neuroendocrine-immune interactions in chronic fatigue syndrome. J Clin Endocrinol Metab. 2000 Feb;85(2):692-6. http://www.ncbi.nlm.nih.gov/pubmed/10690878

 

CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone

Abstract:

A disturbed hypothalamus-pituitary-adrenal gland axis and alterations at the immune system level have been observed in patients with chronic fatigue syndrome (CFS). Glucocorticoids are known to modulate T cell responses; therefore, purified CD4 T cells from CFS patients were studied to determine whether they have an altered sensitivity to dexamethasone (DEX).

CD4 T cells from CFS patients produced less interferon-gamma than did cells from controls; by contrast, interleukin-4 production and cell proliferation were comparable. With CD4 T cells from CFS patients (compared with cells from controls), a 10- to 20-fold lower DEX concentration was needed to achieve 50% inhibition of interleukin-4 production and proliferation, indicating an increased sensitivity to DEX in CFS patients.

Surprisingly, interferon-gamma production in patients and controls was equally sensitive to DEX. A differential sensitivity of cytokines or CD4 T cell subsets to glucocorticoids might explain an altered immunologic function in CFS patients.

 

Source: Visser J, Blauw B, Hinloopen B, Brommer E, de Kloet ER, Kluft C, Nagelkerken L. CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone. J Infect Dis. 1998 Feb;177(2):451-4. http://jid.oxfordjournals.org/content/177/2/451.long