Results of Adrenal and Pituitary Stimulation Tests in Patients With Multiple Sclerosis

Ketelaer, Ch. J.; Delmotte, P.

doi:10.1111/j.1600-0404.1972.tb07568.x

Cited by 5 publications

(4 citation statements)

References 3 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From other studies in patients with MS that measured corticosteroids in plasma and urine at baseline or following stimulation conflicting data emerged, showing increased, decreased or unaltered HPA activity (Cazzullo et al, 1968;Ketelaer & Delmotte, 1972;Klapps et al, 1992;Maida & Summer, 1979;Millac et al, 1969). Following insulin hypoglycemia the plasma cortisol increase was found to be blunted in MS, which was interpreted as indicative of an impaired ability to adapt to a humoral stressor (Teasdale et al, 1967).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of hypothalamic-pituitary-adrenal system response to a combined dexamethasone-CRH test in multiple sclerosis

Grasser¹,

Møller²,

Backmund³

et al. 2009

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

The endocrine system participates in the regulation of the immune and neural systems and therefore hormonal factors probably play an important role in the development and course of multiple sclerosis (MS). Specifically, the hypothalamic-pituitary-adrenal (HPA) system seems crucial because (a) the inflammatory response is accompanied by HPA activation; (b) animal models with an inherited HPA defect are prone to developing experimental autoimmune encephalitis; and (c) most important, corticosteroids are still the most widely used treatment. We administered a recently developed neuroendocrine function test that combines dexamethasone suppression (1.5 mg orally at 2300 h) and corticotropin-releasing hormone (CRH) stimulation (100 micrograms i.v. at 1500 h the following day) and measured the response of plasma cortisol and corticotrophin (ACTH) secretion in 19 patients with an acute exacerbation of MS. These patients had a significantly higher mean plasma cortisol response than age-matched controls (peak minus baseline; 48.1 +/- 10.5 ng/ml [mean +/- SEM] versus 19.8 +/- 4.2 ng/ml; p < 0.05), but the corresponding ACTH values for the two groups were indistinguishable (13.4 +/- 1.4 pg/ml [mean +/- SEM] versus 11.3 +/- 1.4 pg/ml; n.s.). The response range in the patients was broader and we identified six patients with excessive cortisol release (peak minus baseline: 100.5 +/- 14.4 ng/ml [mean +/- SEM]), whereas four patients failed to respond at all. The hormonal response patterns were not related to previous treatments with corticosteroids or other immunosuppressants or to psychopathological features. These results point to a heterogeneity of HPA system function, most likely at the corticosteroid receptor level, which has clinical implications for all those treatments that affect the HPA system and the course of MS.

show abstract

Section: Introductionmentioning

confidence: 99%

Heterogeneity of hypothalamic-pituitary-adrenal system response to a combined dexamethasone-CRH test in multiple sclerosis

Grasser¹,

Møller²,

Backmund³

et al. 2009

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

show abstract

“…Although earlier reports on the regulation of the HPA system in MS yielded variable results (7)(8)(9), recent literature more consistently shows hyperactivity of the HPA axis under basal conditions (10), in dynamic testing (10 -14), or postmortem (15)(16)(17). Using the combined dexamethasone-CRH test (Dex-CRH test), we previously showed hyperactivity of the HPA system in MS patients, which was significantly correlated to the clinical course of MS (12,18).…”

Section: Ultiple Sclerosis (Ms) Is a Chronic Inflammatorymentioning

confidence: 86%

Combined Treatment with Corticosteroids and Moclobemide Favors Normalization of Hypothalamo-Pituitary-Adrenal Axis Dysregulation in Relapsing-Remitting Multiple Sclerosis: A Randomized, Double Blind Trial

Bergh

Kümpfel

Grasser

et al. 2001

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0--6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS.

show abstract

“…Basal plasma cortisol levels have been found to be generally normal [1, 17,21,33,42,45], or elevated in acutely relapsed patients [25], and elevated with a disturbed circadian rhythm and an abnormally low ACTHto-cortisol ratio [24]. In assessing dynamic features of the HPA system, highly variable and often blunted secretion of cortisol following ACTH administration at diagnostic or therapeutic doses is reported, especially in patients with long-standing MS [6, 16,21,39]. Response to insulin-induced hypoglycemia has been found inadequate in a proportion of MS patients in other studies [16,17,42].…”

Section: Introductionmentioning

confidence: 99%

“…In assessing dynamic features of the HPA system, highly variable and often blunted secretion of cortisol following ACTH administration at diagnostic or therapeutic doses is reported, especially in patients with long-standing MS [6, 16,21,39]. Response to insulin-induced hypoglycemia has been found inadequate in a proportion of MS patients in other studies [16,17,42]. Michelson et al [24] reported ACTH secretion to be normal upon injection of CRH but blunted upon vasopressin, suggesting a similar situation as in experimental chronic inflammatory disorders, where vasopressin appears to be the dominant ACTH secretagogue [13].…”

Section: Introductionmentioning

confidence: 99%

Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis

Bergh

Grasser

Trenkwalder

et al. 1999

Journal of Neurology

View full text Add to dashboard Cite

Although the exact etiology of multiple sclerosis (MS) remains unresolved, immune reactions are believed to be the central pathogenic mechanisms. Endogenous and therapeutic steroid hormones affect the immune system, and inflammatory diseases are associated with activation of the hypothalamic-pituitary-adrenal axis, providing evidence of an immune-endocrine interplay. Function tests in MS have revealed dysregulation of the hypothalamic-pituitary-adrenal system in a substantial proportion of patients. We characterized glucocorticoid receptor (GR) binding in peripheral blood lymphocytes from 39 MS patients and 14 age- and sex-matched controls with respect to dissociation constant and binding capacity, using a whole-cell binding assay with [3H]dexamethasone as the ligand. GR binding parameters did not differ significantly between patients (Kd 8.98 +/- 1.07 nM, Bmax 183 +/- 29.8 fmol/mg) and controls (Kd 9.36 +/- 1.17 nM, Bmax 158 +/- 16 fmol/mg). No effect of age, sex, course, duration or severity of disease, or prior steroid treatments was detected. GR binding parameters were analyzed in relation to the results of the combined dexamethasone-CRH test, which reflects corticosteroid receptor function at the hypothalamus, in 30 patients and 9 controls. While controls showed a moderate correlation between binding affinity of the GR in lymphocytes and regulatory function at the hypothalamic level, the patients did not. These data suggest that the physiological relationship between binding and function of the glucocorticoid receptor is disturbed in MS.

show abstract

Results of Adrenal and Pituitary Stimulation Tests in Patients With Multiple Sclerosis

Cited by 5 publications

References 3 publications

Heterogeneity of hypothalamic-pituitary-adrenal system response to a combined dexamethasone-CRH test in multiple sclerosis

Heterogeneity of hypothalamic-pituitary-adrenal system response to a combined dexamethasone-CRH test in multiple sclerosis

Combined Treatment with Corticosteroids and Moclobemide Favors Normalization of Hypothalamo-Pituitary-Adrenal Axis Dysregulation in Relapsing-Remitting Multiple Sclerosis: A Randomized, Double Blind Trial

Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis

Contact Info

Product

Resources

About