Hypothalamic-pituitary-adrenocortical axis function in premenopausal women with rheumatoid arthritis not treated with glucocorticoids

J Rheumatol. 1999 Feb;26(2):282-8.


Objective: To assess hypothalamic-pituitary-adrenocortical axis function in patients with rheumatoid arthritis (RA) not previously treated with glucocorticoids in relation to their inflammatory condition and in comparison to healthy controls.

Methods: We evaluated, in 10 premenopausal patients with RA and 7 age matched controls, plasma dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and cortisol concentrations, together with inflammatory cytokine levels [interleukin 6 (IL-6) and IL-12], both in basal conditions and after stimulation with ovine corticotropin releasing hormone (oCRH) and with low dose intravenous (5 microg) adrenocorticotropic hormone (ACTH).

Results: DHEA and DHEAS basal concentrations were found to be significantly lower (p<0.05) in premenopausal patients with RA than in controls. As expected, significantly higher basal levels of IL-6 and IL-12 (p<0.05) were found in patients with RA. After the low dose ACTH testing, the DHEA area under the curve value was found to be significantly lower (p<0.01) in patients than controls. Similar results, but without statistical significance, were observed after oCRH stimulation. DHEA levels at basal time showed a significant negative correlation with the erythrocyte sedimentation rate and platelet count, as well as with the Steinbrocker class of the disease (p<0.05). Normal plasma cortisol levels during oCRH and ACTH testing were found in patients with RA in spite of their inflammatory condition. After ACTH testing, IL-6 levels decreased significantly (p<0.05), whereas IL-12 levels were unchanged. No significant changes in IL-6 and IL-12 levels were found after oCRH testing.

Conclusion: The abnormal androgen concentrations observed during testing in patients with RA might support the implication of adrenal androgens in the immune/inflammatory cytokine mediated mechanisms involved in the pathophysiology and clinical aspects of RA.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adrenocorticotropic Hormone / pharmacology
  • Adult
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy
  • Corticotropin-Releasing Hormone / pharmacology
  • Dehydroepiandrosterone / blood
  • Dehydroepiandrosterone Sulfate / blood
  • Dexamethasone / pharmacology
  • Estradiol / blood
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / metabolism*
  • Interleukin-12 / blood
  • Interleukin-6 / blood
  • Pituitary-Adrenal System / metabolism*
  • Premenopause / metabolism*
  • Radioimmunoassay
  • Testosterone / blood
  • Time Factors


  • Glucocorticoids
  • Interleukin-6
  • Interleukin-12
  • Testosterone
  • Dehydroepiandrosterone
  • Estradiol
  • Dehydroepiandrosterone Sulfate
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Hydrocortisone