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Adrenocorticotropin, Glucocorticoid, and Androgen Secretion in Patients with New Onset Synovitis/Rheumatoid Arthritis: Relations with Indices of Inflammation¹

Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (K.S.K., M.L.C., C.H.Y., R.L.W.), and National Institute of Child Health and Human Development (G.P.C.), National Institutes of Health, Bethesda, Maryland 20892; and School of Medicine (H.R.S.), University of Pennsylvania, Philadelphia, Pennsylvania 19104

Address all correspondence and requests for reprints to: Keith S. Kanik, M.D., Division of Rheumatology, University of South Florida College of Medicine, Tampa, Florida 33612. E-mail: kkanik{at}com1.med.usf.edu

To determine whether alterations in adrenocortical function occur early in the development of inflammatory joint disease, we examined patients with new onset synovitis (<1 yr) prior to treatment with corticosteroids or other disease-modifying antirheumatic drugs. Thirty-two patients with new onset synovitis, including 15 fitting criteria for rheumatoid arthritis (RA), taking no medications, were referred for study by local rheumatologists; 32 age- and sex-matched healthy individuals were recruited as controls. Patients and controls had blood drawn under identical conditions between 0900 and 1100 h. Plasma ACTH, cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, free and total testosterone, erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor were measured. Compared with controls, patients had higher inflammatory indices (erythrocyte sedimentation rate, C-reactive protein) and lower basal morning levels of free testosterone (lower in males age 45 yr), but similar levels of ACTH, cortisol, DHEA, DHEA sulfate, and total testosterone. In addition, the positive correlations between ACTH-cortisol, ACTH-DHEA, and cortisol-DHEA, observed in the normal controls, were weakened or abolished in the patients (both total and RA subset). No positive relations between inflammatory indices and ACTH or cortisol were noted, yet an inverse correlation between these indices and DHEA and testosterone was observed. Moreover, a steeper age-associated decline in DHEA was observed in our cross-sectional sample of patients with new onset synovitis. We conclude that patients with synovitis (including those fitting criteria for RA) have adrenocortical hormone alterations within a year of disease onset. Paradoxically, these patients have no positive relation between indices of inflammation and ACTH or cortisol, but rather serum androgen levels are inversely correlated with these indices. In addition, the relations between ACTH, the classic stimulus of cortisol and adrenal androgens, and these hormones are weakened or abolished, whereas the negative relation between age and zona reticularis function is steeper than that of controls.

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