Dehydroepiandrosterone Response to the Adrenocorticotropin Test and the Combined Dexamethasone and Corticotropin-Releasing Hormone Test in Patients with Multiple Sclerosis

Kümpfel, Tania; Bergh, Florian Then; Frieß, Elisabeth; Uhr, Manfred; Yassouridis, Alexander; Trenkwalder, Claudia; Holsboer, Florian

doi:10.1159/000054505

Cited by 25 publications

(9 citation statements)

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“…An increased cortisol/DHEAS ratio has been found to be a surrogate for neurodegenerative diseases[31]–[33]. Therefore, an alternative hypothesis is that the cortisol/DHEAS ratio may represent a slightly lower cerebral DHEAS production in relation to cortisol already before the stroke in predisposing patients.…”

Section: Discussionmentioning

confidence: 99%

“…In longitudinal studies, an increased cortisol/DHEAS ratio has been found to accelerate atherosclerosis-related diseases [27] and to be predictive for cardiovascular diseases [28] and all-cause-mortality [29]. In chronic stress [30] and neurodegenerative diseases [31]–[33], higher cortisol and lower serum DHEA and DHEAS values with a consecutive higher cortisol/DHEAS-ratio have been found. In the acute setting, high cortisol and an increased cortisol/DHEAS – ratio upon admission is associated with severity of illness in intensive care patients [34], corresponding to an impaired adrenal androgen action [35].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Value of Dehydroepiandrosterone-Sulfate and Other Parameters of Adrenal Function in Acute Ischemic Stroke

et al. 2013

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Background and PurposeAcute stroke has a high morbidity and mortality. We evaluated the predictive value of adrenal function testing in acute ischemic stroke. MethodsIn a cohort of 231 acute ischemic stroke patients, we measured dehydroepiandrosterone (DHEA), DHEA-Sulfate (DHEAS), cortisol at baseline and 30 minutes after stimulation with 1 ug ACTH. Delta cortisol, the amount of rise in the 1 ug ACTH-test, was calculated. Primary endpoint was poor functional outcome defined as modified Rankin scale 3–6 after 1 year. Secondary endpoint was nonsurvival after 1 year.ResultsLogistic regression analysis showed that DHEAS (OR 1.21, 95% CI 1.01–1.49), but not DHEA (OR 1.01, 95% CI 0.99–1.04), was predictive for adverse functional outcome. Neither DHEA (OR 0.99, 95% CI 0.96–1.03) nor DHEAS (OR 1.10, 95% CI 0.82–1.44) were associated with mortality. Baseline and stimulated cortisol were predictive for mortality (OR 1.41, 95% CI 1.20–1.71; 1.35, 95% CI 1.15–1.60), but only basal cortisol for functional outcome (OR 1.20, 95% CI 1.04–1.38). Delta cortisol was not predictive for functional outcome (OR 0.86, 95% CI 0.71–1.05) or mortality (OR 0.92, 95% CI 0.72–1.17). The ratios cortisol/DHEA and cortisol/DHEAS discriminated between favorable outcome and nonsurvival (both p<0.0001) and between unfavorable outcome and nonsurvival (p = 0.0071 and 0.0029), but are not independent predictors for functional outcome or mortality in multivariate analysis (adjusted OR for functional outcome for both 1.0 (95% CI 0.99–1.0), adjusted OR for mortality for both 1.0 (95% CI 0.99–1.0 and 1.0–1.01, respectively)).ConclusionDHEAS and the cortisol/DHEAS ratio predicts functional outcome 1 year after stroke whereas cortisol levels predict functional outcome and mortality.Trial RegistrationClinicalTrials.gov NCT00390962 (Retrospective analysis of this cohort).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Dehydroepiandrosterone-Sulfate and Other Parameters of Adrenal Function in Acute Ischemic Stroke

et al. 2013

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“…The remaining four subjects did not respond (Grasser et al 1996). Subsequent studies have confirmed that MS patients are able to escape from dexamethasone suppression following challenge with CRF, suggesting a hyperactivity of the HPA axis that is significantly correlated to disease activity (Fassbender et al 1998;Kumpfel et al 1999;Then Bergh et al 1999). However, although one study related this escape to higher depression and anxiety scores in MS patients compared to controls (Fassbender et al 1998), others have not found any evidence to relate the cortisol response to CRF with increased incidence of depression (Kumpfel et al 1999;Then Bergh et al 1999).…”

Section: Is the Hpa Axis Altered In Patients With Autoimmune Disease?mentioning

confidence: 99%

Neuroendocrine Function and Chronic Inflammatory Stress

Harbuz

2002

Experimental Physiology

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The HPA axis and the response to acute stress The end-point of the activation of the HPA axis is the release of glucocorticoids (cortisol in man, corticosterone in rodents) from the adrenal cortex into the general circulation. The synthesis and release of glucocorticoids are controlled by ACTH released from the anterior pituitary gland. ACTH is synthesised from the precursor proopiomelanocortin (POMC) mRNA. The release of ACTH is regulated by the corticotrophin releasing factors corticotrophin-releasing factor(1-41) (CRF) and arginine vasopressin (AVP), which are released from the median eminence and synthesised in the parvocellular cells of the paraventricular nucleus (PVN). Under normal conditions approximately 50 % of these CRF neurons contain AVP; the remainder contain CRF but no vasopressin. CRF and AVP exert a synergistic action on the release of ACTH. The PVN acts as a co-ordinating centre receiving signals from many brain areas to regulate the response to stress. The glucocorticoids are able to regulate their own synthesis by negative feedback mediated by two corticosteroid receptors, the type II (glucocorticoid) receptor, which is found in the pituitary, PVN and other brain areas such as the hippocampus, and the type I receptor, which is found in the hippocampus. The hippocampus has a tonic inhibitory input to the PVN. In response to acute stress, the HPA axis is activated evoking the release of CRF and AVP into the The factors regulating susceptibility and severity of autoimmune diseases are poorly understood. That neuroendocrine factors are critical modulators in this regard is self-evident. For example, there are major gender differences in susceptibility with women at greater risk than men of, for example, rheumatoid arthritis (RA) and multiple sclerosis (MS). The hypothalamo-pituitary-adrenal (HPA) axis has rightly attracted a considerable amount of attention. Of particular interest has been the hypothesis that susceptibility to autoimmune disease may be related to an impaired responsiveness of the HPA axis; that is, an inability to mount an appropriate cortisol response with which to down-regulate the immune system might allow the immune system to rampage unchecked and attack self. This hypothesis links regulation of the release from the adrenal gland of the potent anti-inflammatory glucocorticoids to the disease process. Endogenous glucocorticoids are crucial for the regulation of the severity of the disease process. The hypothesis proposing a link between a hyporesponsive HPA axis and susceptibility to disease is compelling. However, evidence from a number of sources has suggested that this may not be the entire story and alterations in the activity of the HPA axis have not been consistently observed in patients with RA. This review will concentrate on recent findings concerning the HPA axis in determining susceptibility to, and in regulating the severity of, inflammatory processes in autoimmune disease. These studies have revealed that a single exposure to endotoxin can confer protection to sub...

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“…[1][2][3][4][5][6][7][8][9] Interestingly, hypoandrogenicity is a very common phenomenon in many chronic inflammatory diseases. [10][11][12][13][14][15][16][17] In RA and other autoimmune diseases it has been stated that alteration of androgen secretion has an impact on perpetuation of the disease. 18 19 Treatment with dehydroepiandrosterone (DHEA), as the starting-point of androgen conversion (fig 1), has been proved to be a therapeutic alternative in SLE [20][21][22] and, possibly, in patients with chronic inflammatory bowel disease.…”

mentioning

confidence: 99%

Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis

Härle

Pongratz²,

Weidler³

et al. 2004

Annals of the Rheumatic Diseases

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Background: Hypoandrogenicity is common in obesity and in chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Adrenal androgens such as androstenedione (ASD) and dehydroepiandrosterone (DHEA) sulphate are low, which partly depends on the influence of TNF in chronic inflammatory diseases. Leptin is stimulated by TNF and is associated with hypoandrogenicity in non-inflammatory conditions. Objective: To study the interrelation between serum levels of leptin and adrenal steroids in SLE and RA. Methods: In a retrospective study, serum levels of leptin, ASD, DHEA, and 17-hydroxyprogesterone (17OHP) were measured by ELISA, and serum levels of cortisol by radioimmunoassay in 30 patients with RA, 32 with SLE, and 54 healthy control subjects (HS). Results: In SLE and RA but not HS, serum levels of ASD correlated negatively with serum levels of leptin (p,0.01) independently of prior prednisolone treatment in patients with SLE (p = 0.013) and tended to be independent of prednisolone in patients with RA (p = 0.067). In a partial correlation analysis, this interrelation remained significant after controlling for daily prednisolone dose in both patient groups. In both patient groups, serum leptin levels correlated negatively with the molar ratio of serum ASD/serum cortisol and serum ASD/serum 17OHP, and positively with the molar ratio of serum DHEA/serum ASD. Conclusions: The negative correlation of serum leptin and ASD or, particularly, ASD/17OHP, together with its known anti-androgenic effects indicate that leptin is also involved in hypoandrogenicity in patients with SLE and RA. Leptin may be an important link between chronic inflammation and the hypoandrogenic state.

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Dehydroepiandrosterone Response to the Adrenocorticotropin Test and the Combined Dexamethasone and Corticotropin-Releasing Hormone Test in Patients with Multiple Sclerosis

Cited by 25 publications

References 50 publications

Prognostic Value of Dehydroepiandrosterone-Sulfate and Other Parameters of Adrenal Function in Acute Ischemic Stroke

Prognostic Value of Dehydroepiandrosterone-Sulfate and Other Parameters of Adrenal Function in Acute Ischemic Stroke

Neuroendocrine Function and Chronic Inflammatory Stress

Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis

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