title: Increased DHEAS levels in patients with rheumatoid arthritis after treatment with tumor necrosis factor antagonists: evidence for improved adrenal function.
abstract: OBJECTIVE
  To determine if major reduction of inflammation with longterm tumor necrosis factor (TNF) antagonist treatment has any influence on the adrenal and gonadal axes in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Forty-eight patients with RA were treated with infliximab or etanercept for 2 years. Disease activity, clinical response, and physical function were evaluated and serum levels of high sensitivity C-reactive protein and interleukin 6 were analyzed before start of treatment and after 1 and 2 years. At the same timepoints adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone sulfate (DHEAS) were analyzed; luteinizing hormone (LH), estradiol, and testosterone were analyzed as well in 18 male patients.
  
  
  RESULTS
  DHEAS increased (p <or= 0.05) after 1 and 2 years of treatment with TNF antagonists. No change in serum levels of ACTH, cortisol, LH, estradiol, or testosterone was recorded during the 2 years. The increased levels of DHEAS correlated with improved physical function measured by Health Assessment Questionnaire (p <or= 0.01). There was no correlation between hormone levels and clinical response or inflammatory markers. A longitudinal stability in individual hormone levels was found between baseline and 2 years, most markedly for DHEAS levels (rs = 0.90, p <or= 0.01). A female subgroup characterized by low levels of DHEAS had a lower age at disease onset.
  
  
  CONCLUSIONS
  The increased DHEAS levels may indicate an improved adrenal function during 2 years' treatment with TNF antagonists. Improved physical function, correlated to increased DHEAS levels, may be an effect of better adrenal function during powerful antiinflammatory treatment. The stability in individual hormone levels suggests a stable hormonal homeostasis, independent of inflammatory activity.
authors.affiliation: Department of Rheumatology, Division of Clinical Chemistry, Karolinska Institute at Karolinska University Hospital, Huddinge, Stockholm, Sweden. sofia.ernestam@karolinska.se
authors.forename: Sofia
authors.initials: S
authors.lastname: Ernestam
authors.forename: Ingiäld
authors.initials: I
authors.lastname: Hafström
authors.forename: Sigbritt
authors.initials: S
authors.lastname: Werner
authors.forename: Kjell
authors.initials: K
authors.lastname: Carlström
authors.forename: Birgitta
authors.initials: B
authors.lastname: Tengstrand
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000032:analysis; D003687:Dehydroepiandrosterone / Q000097:blood*; D000068800:Etanercept; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006304:Health Status; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007074:Immunoglobulin G / Q000627:therapeutic use*; D000069285:Infliximab; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D012739:Gonadal Steroid Hormones; D007074:Immunoglobulin G; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003687:Dehydroepiandrosterone; D002097:C-Reactive Protein; D000069285:Infliximab; D000068800:Etanercept