Perspectives on the relationship of adrenal steroids to rheumatoid arthritis

An expanded model of RA is presented that incorporates cumulative multifactorial processes operating over a prolonged physiological phase prior to initial clinical manifestations. During this phase, progressive imbalances in the homeostasis of core neuroendocrine, immunological, and microvascular systems are believed to occur. Normal adrenal function plays an essential role in helping to maintain homeostasis of core systems in health. In RA, chronic adrenal hypocompetence is suspected to occur in a minority subset of females who have younger clinical onset and males who have associated low serum testosterone levels. Chronic, relative glucocorticoid insufficiency is believed to contribute to development of inflammatory manifestations in RA patients. Androgenic deficiencies, particularly of gonadal origin in males, may also contribute to RA, particularly its decreased anabolic features. Precise influences of hypocompetent adrenal steroid function on long-term modeling of the immunological compartment and control of microvascular activation processes are not well understood. These complex mechanisms need to be elucidated for better understanding of the physiopathogenesis of RA. Nevertheless, at a clinical level, sufficient data are currently available to endorse further controlled studies of early clinical onset patients and prospective investigations to determine more definitively the roles of adrenal (and gonadal) steroids in subsets of RA patients and unaffected susceptible persons in the population.