Plasma Dehydroepiandrosterone, Dehydroepiandrosterone Sulphate and Androsterone Sulphate Levels and Their Interaction with Plasma Proteins in Rheumatoid Arthritis

Fehér, Katalin G.; Fehér, T

doi:10.1055/s-0029-1210387

Cited by 23 publications

(3 citation statements)

References 6 publications

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“…DHEAS levels were also associated with both severity 19 and duration of RA 16 as well as with higher mortality, 20 and coronary heart disease. 21 Decreased levels of 4-androsten-3beta,17-beta-diol disulfate 2, 17 androsterone sulfate, 22 and cortisol 17 were previously observed in RA patients compared with controls. Lower levels of 4-androsten-3-beta,17-beta-diol disulfate 2 (androstenediol), a metabolite in the pathway of dehydroepiandrosterone (DHEA), 17 were observed in prerheumatoid arthritis subjects 17 and correlated with lower levels of cortisol in the same patient population.…”

Section: Diagnostic Analysismentioning

confidence: 78%

“…Lower levels of 4-androsten-3-beta,17-beta-diol disulfate 2 (androstenediol), a metabolite in the pathway of dehydroepiandrosterone (DHEA), were observed in prerheumatoid arthritis subjects and correlated with lower levels of cortisol in the same patient population . Lower androsterone sulfate levels were observed in RA patients irrespective of their age ranges. These steroids as well as the putative steroids (X-12844, X-11444, and X-11470) have shown their highest significance on comparing groups that have JI symptoms to controls (Table ), suggesting that the chronic inflammation or polyarthritis self-reported symptoms affects steroid metabolism more obviously than does the worn-out joint (WO) symptom; however, there is not enough statistical power to confirm that observation.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic and Prognostic Metabolites Identified for Joint Symptoms in the KORA Population

et al. 2016

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This study aims at identifying metabolites that significantly associate with self-reported joint symptoms (diagnostic) and metabolites that can predict the change from a symptom-free status to the development of self-reported joint symptoms after a 7 years period (prognostic). More than 300 metabolites were analyzed for 2246 subjects from the longitudinal study of the KORA (Cooperative Health Research in the Region of Augsburg, Germany), specifically the fourth survey S4 and its 7-year follow-up study F4. Two types of self-reported symptoms, chronic joint inflammation and worn out joints, were used for the analyses. Diagnostic analysis identified dysregulated metabolites in cases with symptoms compared with controls. Prognostic analysis identified metabolites that differentiate subjects in S4 who remained symptom-free after 7 years (F4) from those who developed any combination of symptoms. 48 metabolites were identified as nominally significantly (p < 0.05) associated with the self-reported symptoms in the diagnostic analysis, among which steroids show Bonferroni significance. 45 metabolites were identified as nominally significantly associated with developing symptoms after 7 years, among which hippurate showed Bonferroni significance. We show that metabolic profiles of self-reported joint symptoms are in line with metabolites known to associate with various forms of arthritis and suggest that future studies may benefit from that by investigating the possible use of self-reporting/questionnaire along with metabolic markers for the early referral of patients for further diagnostic workup and treatment of arthritis.

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Section: Diagnostic Analysismentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Diagnostic and Prognostic Metabolites Identified for Joint Symptoms in the KORA Population

et al. 2016

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“…In contrast, we have recently shown that DHEA also undergoes similar intracrine processing in human salivary glands and that particularly conversion of DHEA to dihydrotestosterone is impaired in Sjögren's syndrome, probably at least in part due to a deficiency of type I 5α‐reductase (18, 19). It may therefore be that the impaired synthesis of DHEA in the reticular zone of the cortex of the suprarenal gland in Sjögren's syndrome only represents a premature adrenopause or inhibition of DHEA synthesis as is seen secondary to autoimmune inflammation in rheumatoid arthritis and systemic lupus erythematosus (20–22). This further aggravates the local intracrine conversion defect in salivary glands.…”

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA‐deficient patients with primary Sjögren's Syndrome

Virkki¹,

Porola²,

Forsblad-d’Elia³

et al. 2009

Arthritis Care & Research

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Objective. Primary Sjö gren's syndrome (SS) is characterized by fatigue and low levels of serum dehydroepiandrosterone/ dehydroepiandrosterone sulfate (DHEA/DHEAS). Our aim was to study whether SS patients with severe fatigue and low serum DHEAS values benefit from DHEA substitution (50 mg/day). Methods. A multicenter, investigator-based, powered, randomized controlled clinical trial (crossover, washout design) using fatigue as the primary outcome measure was performed on patients with primary SS (n ‫؍‬ 107) who had a general fatigue score >14 on the 20-item Multiple Fatigue Inventory (MFI-20), combined with age-and sex-adjusted serum DHEAS values below the mean. Fatigue was assessed using MFI-20 subscales, i.e., general fatigue, physical fatigue, mental fatigue, reduced motivation, and activity (scale 4 -20), and with a visual analog scale (VAS; scale 0 -100). Results. In an intent-to-treat analysis, a 50-mg DHEA substitution dose and placebo similarly improved fatigue. All of the MFI-20 subscales and the fatigue VAS improved from the baseline levels as a result of treatment (P < 0.001), but with negligible differences between these 2 treatments. The mean between-treatment difference was ؊0.1 for general fatigue (the primary outcome measure), 0.0 for physical fatigue, 0.0 for mental fatigue, 0.0 for reduced motivation, 0.3 for reduced activity, and 2.2 for the fatigue VAS. None of these differences was statistically significant. Conclusion. Similar to earlier results using pharmacologic doses, substitution treatment with 50 mg of DHEA in DHEA-deficient and severely tired primary SS patients does not help against fatigue better than placebo. This may relate to the prohormone nature of DHEA and its recently described defective intracrine tissue-specific conversion to active sex steroids in SS.

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Tumor necrosis factor inhibits conversion of dehydroepiandrosterone sulfate (DHEAS) to DHEA in rheumatoid arthritis synovial cells: A prerequisite for local androgen deficiency

Weidler¹,

S²,

Schmidt³

et al. 2005

Arthritis & Rheumatism

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Objective. Use of anti-tumor necrosis factor (anti-TNF) antibody therapy in rheumatoid arthritis (RA) has expanded our understanding of possible mechanisms by which this treatment reduces inflammation. Beyond its effects on local immune responses, anti-TNF treatment may also modulate the local hormone supply. Because androgens are thought to inhibit immune responses, their presence in inflamed tissue is an additional important antiinflammatory factor.Methods. We investigated conversion of the ubiquitous dehydroepiandrosterone sulfate (DHEAS), the biologically inactive precursor of DHEA, to the androgen DHEA in mixed synovial cells from patients with RA and patients with osteoarthritis (OA), making use of thin-layer chromatography and phosphorimaging. Using immunohistochemical analysis, we detected the key enzyme, steroid sulfatase.Results. DHEAS-to-DHEA conversion in synovial cells from patients with RA was significantly lower than that in synovial cells from patients with OA (mean ؎ SEM 3.3 ؎ 0.5% versus 6.0 ؎ 0.9% of applied 3 H-DHEAS per 10 6 synovial cells; P ‫؍‬ 0.042). In RA, but not in OA, the level of converted 3 H-DHEA was inversely correlated with the density of synovial macrophages (for RA, R rank ‫؍‬ ؊0.725, P ‫؍‬ 0.005; for OA, R rank ‫؍‬ 0.069, P not significant [NS]) and T cells (for RA, R rank ‫؍‬ ؊0.621, P ‫؍‬ 0.024; for OA, R rank ‫؍‬ 0.247, P NS). Double immunohistochemistry analysis revealed that steroid sulfatase was located mainly in synovial macrophages but was also observed in fibroblasts. Neutralization of TNF largely up-regulated the conversion of DHEAS to DHEA in RA, but not in OA. A similar neutralizing effect was observed with polyclonal human immunoglobulins; this effect is most probably mediated via TNF neutralization at low TNF concentrations.Conclusion. These data indicate that TNF inhibits the conversion of DHEAS to DHEA in RA synovial cells. Because androgens are antiinflammatory mediators, TNF-induced inhibition of the local androgen supply is a supplementary proinflammatory factor. Consequently, anti-TNF strategies may also exert their positive effects by increasing tissue androgens.

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Plasma Dehydroepiandrosterone, Dehydroepiandrosterone Sulphate and Androsterone Sulphate Levels and Their Interaction with Plasma Proteins in Rheumatoid Arthritis

Cited by 23 publications

References 6 publications

Diagnostic and Prognostic Metabolites Identified for Joint Symptoms in the KORA Population

Diagnostic and Prognostic Metabolites Identified for Joint Symptoms in the KORA Population

Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA‐deficient patients with primary Sjögren's Syndrome

Tumor necrosis factor inhibits conversion of dehydroepiandrosterone sulfate (DHEAS) to DHEA in rheumatoid arthritis synovial cells: A prerequisite for local androgen deficiency

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