title: The hypothalamic-pituitary-adrenocortical and gonadal axis function in rheumatoid arthritis.
abstract: The altered cortisol and adrenal androgen (i.e., dehydroepiandrosterone sulfate = DHEAS) secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with corticosteroids, should be clearly regarded as a "relative adrenal insufficiency" in the setting of a sustained inflammatory process, as shown by high serum IL-6 levels. Androgens seem implicated in the pathophysiology of autoimmune disorders, including RA, as natural immunosuppressors. Low plasma and synovial fluid testosterone concentrations are observed in male RA patients; low plasma DHEAS levels are mainly observed in female RA patients. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). Gene polymorphisms for enzymes involved in the steroidogenesis seem to further complicate the role of sex hormones in the susceptibility to autoimmunity. Acquired changes of sex steroid metabolism seem to also play a role in the peripheral sex hormone levels. In conclusion, a complex interaction between the hypothalamus-pituitary-adrenocortical and gonadal axis functions is evident in RA.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Genova-Italy, Viale Benedetto XV, 6 I-16132 Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cutolo
authors.forename: M
authors.initials: M
authors.lastname: Giusti
authors.forename: L
authors.initials: L
authors.lastname: Foppiani
authors.forename: B
authors.initials: B
authors.lastname: Seriolo
authors.forename: M
authors.initials: M
authors.lastname: Briata
authors.forename: A
authors.initials: A
authors.lastname: Bisso
authors.forename: F
authors.initials: F
authors.lastname: Faelli
authors.forename: L
authors.initials: L
authors.lastname: Felli
authors.forename: C
authors.initials: C
authors.lastname: Prete
authors.forename: C
authors.initials: C
authors.lastname: Pizzorni
authors.forename: A
authors.initials: A
authors.lastname: Sulli
mesh_terms: D000309:Adrenal Insufficiency / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D013739:Testosterone / Q000097:blood*
chemical_list: D015850:Interleukin-6; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D006854:Hydrocortisone