Adrenocorticotropin, glucocorticoid, and androgen secretion in patients with new onset synovitis/rheumatoid arthritis: Relations with indices of inflammation

To determine whether alterations in adrenocortical function occur early in the development of inflammatory joint disease, we examined patients with ne w onset synovitis (<1 yr) prior to treatment with corticosteroids or other disease-modifying antirheumatic drugs. Thirty-two patients with new onset s ynovitis, including 15 fitting criteria for rheumatoid arthritis (RA), taki ng 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 11 00 h. Plasma ACTH, cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, f ree and total testosterone, erythrocyte sedimentation rate, C-reactive prot ein, 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 mal es age greater than or equal to 45 yr), but similar levels of ACTH, cortiso l, DHEA, DHEA sulfate, and total testosterone. In addition, the positive co rrelations between ACTH-cortisol, ACTH-DHEA, and cortisol-DHEA, observed in the normal controls, were weakened or abolished in the patients (both tota l and RA subset). No positive relations between inflammatory indices and AC TH 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 wit h new onset synovitis. We conclude that patients with synovitis (including those fitting criteria for RA) have adrenocortical hormone alterations with in a year of disease onset. Paradoxically, these patients have no positive relation between indices of inflammation and ACTH or cortisol, but rather s erum androgen levels are inversely correlated with these indices. In additi on, the relations between ACTH, the classic stimulus of cortisol and adrena l androgens, and these hormones are weakened or abolished, whereas the nega tive relation between age and zona reticularis function is steeper than tha t of controls.