DESMOPRESSIN AND LOW-DOSE ACTH TEST IN RHEUMATOID-ARTHRITIS

Objective: To ascertain whether a different regulation and sensitivity of the hypothalamic-pituitary-adrenal axis exists and whether a type of cortisol resistance is present in rheumatoid arthritis (RA) patient s, a chronic disease in whose pathogenesis modifications of the steroi d milieu are involved. Design: We studied the basal and dynamic respon se of ACTH and adrenal steroids to various stimuli acting on the hypop hysis or directly on the adrenal gland.Methods: We studied ten RA pati ents (39.8 +/- 7.4 (S.D.) years), defined according to the American Rh eumatism Association, and seven healthy control patients (34.1 +/- 9.6 (S.D.) years). All subjects underwent testing, in random order, with placebo, desmopressin (DDAVP) (10 mu g i.v.), ovine corticotrophin-rel easing hormone (oCRH) (1 mu g/kg body weight) and low-dose ACTH (5 mu g i.v.), during the follicular phase of two different menstrual cycles . Blood samples were collected at different times for ACTH and adrenal steroids assay. Baseline estradiol (E2), testosterone and IGF-I level s were also evaluated. All subjects collected urine specimens for 24 h urine free cortisol (UFC). Results: No difference in E2, testosterone or UFC was found between RA patients and controls. IGF-I levels were significantly (P < 0.01) lower in RA patients (110.6 +/- 6.4 mu g/l) t han in controls (207.0 +/- 37.9 mu g/l). Mean baseline dehydroepiandro sterone (DHEA) and Delta 4-androstenedione levels of the four tests we re significantly (P < 0.05) lower in RA patients than in controls. In RA, a negative correlation was found between mean DHEA levels, class o f disease (r = -0.67, P < 0.05) and erythrocyte sedimentation rate (r = -0.63, P < 0.05). After placebo no difference in ACTH and cortisol a rea under curves (AUCs) was found between RA patients and controls. Af ter DDAVP no cortisol or ACTH response was found in RA patients, while a significant (P < 0.01) DHEA increase. After oCRH a similar signific ant response in ACTH (P < 0.05), cortisol (P < 0.01), and DHEA (P < 0. 01) was found in both groups. After low-dose ACTH, a similar significa nt (P < 0.01) cortisol response was found in both RA patients and cont rols; indeed in RA patients DHEA AUC (2196.0 +/- 321.8 nmol/l per 90 m in) was significantly lower (P < 0.01) than DHEA AUC (4280.8 +/- 749.0 nmol/l per 90 min) in controls. A similar significant (P < 0.01), tho ugh not abnormal, 17-hydroxyprogesterone response to ACTH was found in both groups. Conclusions: Our study underlines reduced adrenal steroi d and IGF-I levels, but not the previously described cortisol resistan ce in RA patients; it shows that baseline and dynamic cortisol levels are 'normal' but inadequate in the setting of a sustained inflammatory disease like RA. The reduced basal and low-dose ACTH-induced DHEA lev els could reflect both a reduced sensitivity of the adrenal gland to e xogenous corticotrophin and a decreased steroid synthesis due to a par tial adrenal enzymatic defect.