Determinants of adrenal androgen hypofunction in premenopausal females with rheumatoid arthritis.

The aim of our study was to investigate adrenocortical function in the context of disease activity and inflammatory status in premenopausal RA females. Adrenal glucocorticoid and androgen responses to the 1 microg ACTH 1-24 test were investigated in 23 premenopausal RA and in 15 age- and BMI-matched healthy females. Twelve RA patients were on low-dose prednisone (<8.5 mg/day). Patients with DAS28>3.2 had lower (p<0.05) total plasma cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone and androstenedione responses in the ACTH test compared to healthy controls. Patients with DAS28>3.2 had lower (p<0.05) dehydroepiandrosterone response in the ACTH test compared to patients with DAS28

Measurement of salivary aldosterone: validation by low-dose ACTH test and gender differences.

The aim of the present study was to validate the feasibility of measurement of the salivary aldosterone concentrations by performing a low-dose adrenocorticotropic hormone (ACTH) test. Moreover, the presence of gender differences in salivary aldosterone, considering the phase of the menstrual cycle in women, was verified. The sample consisted of 107 volunteers (60 men, 21 women in the follicular phase and 26 women in the luteal phase of the menstrual cycle). Saliva samples were taken by the subjects themselves around 08:00 AM, at least 60 min after awaking. A separate group of female subjects in the follicular phase underwent low-dose ACTH test (1µg synthetic ACTH i.v.) performed at 08:30 AM with blood and saliva sampling every 30 min for 120 min. Modification of the commercial aldosterone radioimmunoassay methodology for the salivary aldosterone measurement was performed. Salivary aldosterone concentrations rose in response to low-dose ACTH test and positive significant correlation in aldosterone concentrations between plasma and saliva was found. The results showed that women in the luteal phase of the menstrual cycle exhibited significantly higher morning concentrations in salivary aldosterone than men and women in the follicular phase. This study clearly demonstrates suitability of measurement of salivary aldosterone concentrations in the low-dose ACTH test and reveals gender differences in salivary aldosterone levels. The results show high validity of the presented method and its usefulness for assessment of the aldosterone concentrations in saliva.

Chronic inflammation and low-dose glucocorticoid effects on glucose metabolism in premenopausal females with rheumatoid arthritis free of conventional metabolic risk factors.

Chronic systemic inflammation is associated with increased cardiovascular mortality in patients with rheumatoid arthritis (RA). The aim of our study was to investigate association of glucose metabolism and inflammatory markers in a group of patients with rheumatoid arthritis free of other metabolic risk factors. Twenty-two premenopausal RA females (11 patients on low-dose GC (<8.5 mg/day of prednisone or equivalent), 11 patients without glucocorticoid therapy) and 15 age- and BMI-matched healthy females underwent the oral glucose tolerance test. The insulin sensitivity indices according Matsuda (ISI(MAT)) and Cederholm (ISI(CED)) as well as HOMA2 %S were calculated. Cytokines, lipid profile, non-esterified fatty acids (NEFA) and plasminogen activator inhibitor-1 (PAI-1) were measured in baseline blood samples. Despite elevated interleukin IL-6 and TNF alpha, glucose, insulin and C-peptide responses to oral glucose load as well as ISI(MAT), ISI(CED), PAI-1 and NEFA were comparable in both RA groups and healthy controls. HOMA2 %S correlated with disease activity. In conclusions, low-dose glucocorticoid treatment does not lead to glucose metabolism impairment in RA patients without other metabolic risk factors. Increased cardiovascular mortality and morbidity is probably due to a direct effect of systemic inflammation on myocardium and/or blood vessels.

[Evaluation of 11beta-hydroxysteroid dehydrogenase type 1 activity in female patients with rheumatoid arthritis]. / Hodnotenie aktivity 11beta-hydroxysteroid dehydrogenázv typu 1 u pacientiek s reumatoidnou artritídou.

INTRODUCTION: Cortisol levels in patients with rheumatoid arthritis (RA) are considered inadequate to ongoing inflammation. One possible mechanism ofthe relative cortisol deficit can be decreased 11beta-hydroxysteroid dehydrogenase type 1 (11BHSD1) activity, an enzyme that converts inactive cortisone to active cortisol. The aim of the study was to determine systemic and local activity of 11 BHSD1 in female patients with RA. METHODS: Six female RA patients without glucocorticoid therapy (age 29 +/- 2 years, BMI 21 +/- 1 kg/m2) and six healthy women (age 30 +/- 2 years, BMI 21 +/- 1 kg/m2) were studied. Endogenous cortisol production was suppressed by dexamethasone. 11BHSD1 activity was evaluated by changes in concentrations of total plasma, free plasma, salivary and cortisol in subcutaneous adipose tissue after cortisone acetate administration (25 mg per os). RESULTS: Concentrations of total plasma, free plasma, salivary, and tissue cortisol increased significantly, however there was no significant difference between RA patients and controls. CONCLUSION: The result suggests comparable systemic and adipose tissue conversion of cortisone to cortisol. Despite chronic inflammation, systemic activity of 11BHSD1 is not responsible for relative adrenal deficiency in RA. Changes in local activity of the enzyme in tissues affected by inflammatory process cannot be excluded.

Effects of endogenous and exogenous hypercortisolemia on low-dose adrenocorticotropin test outcome in humans.

BACKGROUND: The results of low-dose ACTH testing may be impaired during endogenous or exogenous hypercortisolemia in various clinical situations. AIM: The hypothesized inhibitory effects of hypercortisolemia on adrenal responsiveness to low-dose ACTH were tested in two model situations in healthy humans. SUBJECTS AND METHODS: Nine young healthy women underwent low-dose ACTH test in 5 modifications. In ACTH-ACTH test, ACTH (1 microg iv) was given at 09:00 h and 10:00 h. Two control tests consisted of single ACTH bolus at 09:00 h or at 10:00 h. In hydrocortisone (HC)-ACTH test, HC (20 mg po) was given at 08:30 h and ACTH was injected at 10:00 h. Control test consisted of single HC administration at 08:30 h. RESULTS: Cortisol response after the 2nd ACTH test was significantly lower vs the 1st ACTH bolus (Deltamax: 166+/-32 nmol/l vs 276+/-15 nmol/l, p<0.05) in ACTH-ACTH test. Responses of other steroids after both ACTH injections were comparable. ACTH bolus during HC-induced hypercortisolemia caused a slight increase in cortisol level and prevented its decrease, seen after HC administration alone. Adrenal cortisol production in response to ACTH bolus under different incipient conditions (baseline, physiological, and pharmacological hypercortisolemia; 180+/-16, 173+/-21, and 177+/-53 nmol.min.l-1, respectively) did not significantly differ (p=0.8). CONCLUSIONS: Endogenous and exogenous hypercortisolemia did not influence adrenal cortisol response to low-dose ACTH test indicating lack of its negative feedback at adrenal level.