The hypothalamic-pituitary-adrenocortical and gonadal axis function in rheumatoid arthritis

The altered cortisol and adrenal androgen (i.e., dehydroepiandrosterone sul fate = DHEAS) secretion, observed during testing in rheumatoid arthritis (R A) patients not treated with corticosteroids, should be clearly regarded as a "relative adrenal insufficiency" in the setting of a sustained inflammat ory process, as shown by high serum IL-6 levels. Androgens seem implicated in the pathophysiology of autoimmune disorders, including RA, as natural im munosuppressors. Low plasma and synovial fluid testosterone concentrations are observed in male RA patients; low plasma DHEAS levels are mainly observ ed in female RA patients. The menopausal peak of RA suggests that estrogens and/or progesterone defic iency also play a role in the disease, and many data indicate that estrogen s suppress cellular immunity, but stimulate humoral immunity (i.e., deficie ncy promotes cellular Th 1-type immunity). Gene polymorphisms for enzymes i nvolved in the steroidogenesis seem to further complicate the role of sex h ormones in the susceptibility to autoimmunity. Acquired changes of sex ster oid metabolism seem to also play a role in the peripheral sex hormone level s. In conclusion, a complex interaction between the hypothalamus-pituitary- adrenocortical and gonadal axis functions is evident in RA.