Abstract
Rheumatoid arthritis (RA) is associated with neuroendocrine and immunologic dysfunction leading to rheumatoid cachexia. Although excess proinflammatory cytokines can decrease somatotropic axis activity, little is known about the effects of RA on growth hormone/insulin-like growth factor-1 (GH/IGF-I) axis function. We tested the hypothesis that patients with active RA exhibit decreased GH/IGF-I axis activity. To do so, we conducted a pilot case-control study at a clinical research center in 7 pre- and perimenopausal women with active RA and 10 age- and body mass index-matched healthy women. Participants underwent blood sampling every 20 minutes for 24 hours (8 a.m. to 8 a.m.), and sera were assayed for GH, cortisol, and dehydroepiandrosterone (DHEA). Sera obtained after overnight fasting were assayed for IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, C-reactive protein (CRP), interleukin-6 (IL-6), glucose, insulin, and lipids. Body composition and bone mineral density were evaluated by DEXA (dual emission x-ray absorptiometry) scans. In patients with RA, mean disease duration was 7.6 ± 6.8 years, and erythrocyte sedimentation rate, CRP, and IL-6 were elevated. GH half-life was shorter than in control subjects (p = 0.0037), with no other significant group differences in GH deconvolution parameters or approximate entropy scores. IGF-I (p = 0.05) and IGFBP-3 (p = 0.058) were lower, whereas IGFBP-1 tended to be higher (p = 0.066), in patients with RA, with nonsignificantly increased 24-hour total GH production rates. There were no significant group differences in cortisol or DHEA secretion. Lean body mass was lower in patients with RA (p = 0.019), particularly in the legs (p = 0.01). Women with active RA exhibit a trend toward GH insensitivity and relatively diminished diurnal cortisol and DHEA secretion for their state of inflammation. Whether these changes contribute to rheumatoid cachexia remains to be determined.NCT00034060.
Highlights
Rheumatoid arthritis (RA) is a chronic, autoimmune-mediated, inflammatory arthritis that occurs in approximately 0.5% to 1%of the general population and affects women 2.5 times more often than it does men
Patients were allowed to be on stable doses of methotrexate, but past use of all other disease-modifying agents or anti-tumor necrosis factor (TNF) agents or glucocorticoid was allowed only if (a) the total exposure had not been more than 3 months and (b) there had been no exposure in the 3 months prior to enrollment
Patient characteristics There were no significant differences in age or body mass index (BMI) between patients with RA and control subjects
Summary
Rheumatoid arthritis (RA) is a chronic, autoimmune-mediated, inflammatory arthritis that occurs in approximately 0.5% to 1%of the general population and affects women 2.5 times more often than it does men. ACTH = adrenocorticotropic hormone; ApEn = approximate entropy; BMD = bone mineral density; BMI = body mass index; CRH = corticotropinreleasing hormone; CRP = C-reactive protein; CV = coefficient of variation; DEXA = dual energy x-ray absorptiometry; DHEA = dehydroepiandrosterone; ESR = erythrocyte sedimentation rate; FSH = follicle-stimulating hormone; GFR = glomerular filtration rate; GH = growth hormone; HDL = high-density lipoprotein; HPA = hypothalamic-pituitary-adrenal; IGF-I = insulin-like growth factor-1; IGFBP = insulin-like growth factor-binding protein; IL-6 = interleukin-6; IV = intravenous; LBM = lean body mass; MDRD = Modification of Diet in Renal Disease; NIH = National Institutes of Health; RA = rheumatoid arthritis; RIA = radioimmunoassay; TNF = tumor necrosis factor. The hypothalamic-pituitary-adrenal (HPA) axis is affected to varying degrees in patients with RA, independent of the use of exogenous glucocorticoids. Most reports indicate that circulating levels of cortisol and dehydroepiandrosterone (DHEA) are normal, and not elevated, in the setting of increased proinflammatory activity, suggesting a relative hypoadrenalism in patients with RA, possibly due to reduced corticotropin-releasing hormone (CRH) activity [8,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
