Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis

Hypothalamic-pituitary-adrenal underactivity has been reported in rheumatoi d arthritis (RA). This phenomenon has implications with regard to the patho genesis and treatment of the disease. The present study was designed to eva luate the secretion of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) and its relation to clinical variables in RA, spondyloarthropathy ( Spa), and undifferentiated inflammatory arthritis (UIA). Eighty-seven patie nts (38 with RA, 29 with Spa, and 20 with UIA) were studied, of whom 54 wer e women. Only 12 patients (14%) had taken glucocorticoids previously. Age-m atched, healthy women (134) and men (149) served as controls. Fasting blood samples were taken for determination of the erythrocyte sedimentation rate (ESR), serum DHEAS and insulin, and plasma glucose. Insulin resistance was estimated by the homeostasis-model assessment (HOMA(IR)). DHEAS concentrat ions were significantly decreased in both women and men with inflammatory a rthritis (IA) (P < 0.001). In 24 patients (28%), DHEAS levels were below th e lower extreme ranges found for controls. Multiple intergroup comparisons revealed similarly decreased concentrations in each disease subset in both women and men. After the ESR, previous glucocorticoid usage, current treatm ent with nonsteroidal antiinflammatory drugs, duration of disease and HOMA( IR) were controlled for, the differences in DHEAS levels between patients a nd controls were markedly attenuated in women (P = 0.050) and were no longe r present in men (P = 0.133). We concluded that low DHEAS concentrations ar e commonly encountered in IA and, in women, this may not be fully explainab le by disease-related parameters. The role of hypoadrenalism in the pathoph ysiology of IA deserves further elucidation. DHEA replacement may be indica ted in many patients with IA, even in those not taking glucocorticoids.