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) patients, a chronic disease in whose pathogenesis modifications of the steroid milieu are involved.


METHODS
We studied the basal and dynamic response of ACTH and adrenal steroids to various stimuli acting on the hypophysis or directly on the adrenal gland.


METHODS
We studied ten RA patients (39.8 +/- 7.4 (S.D.) years), defined according to the American Rheumatism 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 microg i.v.), ovine corticotropin-releasing hormone (oCRH) (1 microg/kg body weight) and low-dose ACTH (5 microg 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 levels 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 microg/l) than in controls (207.0 +/- 37.9 microg/l). Mean baseline dehydroepiandrosterone (DHEA) and delta4-androstenedione levels of the four tests were significantly (P < 0.05) lower in RA patients than in controls. In RA, a negative correlation was found between mean DHEA levels, class of 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 area under curves (AUCs) was found between RA patients and controls. After DDAVP no cortisol or ACTH response was found in RA patients, while a significant (P < 0.05) ACTH release was found in controls. Only in RA patients was DDAVP able to induce a significant (P < 0.01) DHEA increase. After oCRH a similar significant 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 significant (P < 0.01) cortisol response was found in both RA patients and controls; indeed in RA patients DHEA AUC (2196.0 +/- 321.8 nmol/l per 90 min) 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), though not abnormal, 17-hydroxyprogesterone response to ACTH was found in both groups.


CONCLUSIONS
Our study underlines reduced adrenal steroid and IGF-I levels, but not the previously described cortisol resistance 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 levels could reflect both a reduced sensitivity of the adrenal gland to exogenous corticotropin and a decreased steroid synthesis due to a partial adrenal enzymatic defect (P450 17,20 lyase).
Foppiani
L
L
Cattedra di Endocrinologia, DiSEM, Universita' di Genova, Italy.
Cutolo
M
M
Sessarego
P
P
Sulli
A
A
Prete
C
C
Seriolo
B
B
Giusti
M
M
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects* / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D015331:Cohort Studies; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D008875:Middle Aged; D010912:Pituitary-Adrenal Function Tests / Q000379:methods; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D012016:Reference Values; D012756:Sheep
D003687:Dehydroepiandrosterone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003894:Deamino Arginine Vasopressin; D006854:Hydrocortisone