EXTENDED REPORT

Low levels of dehydroepiandrosterone sulphate in plasma, and reduced sympathoadrenal response to hypoglycaemia in premenopausal women with rheumatoid arthritis

R Imrich¹, J Rovensky², F Malis², M Zlnay², Z Killinger³, R Kvetnansky¹, M Huckova¹, M Vigas¹, L Macho¹, J Koska¹

¹ Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia
² National Institute of Rheumatic Diseases, Piestany, Slovakia
³ 1st Clinic of Internal Medicine, Medical Faculty of Comenius University in Bratislava, Slovakia

Correspondence to:
Correspondence to:
Dr R Imrich
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06 Bratislava, Slovakia; richard.imrich{at}savba.sk

Objectives: To evaluate the function of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in premenopausal women with rheumatoid arthritis (RA).

Methods: Insulin-induced hypoglycaemia (0.1 IU/kg) was produced in 15 glucocorticoid-naive patients with long term RA with low disease activity and in 14 healthy women matched for age and body mass index. Concentrations of glucose, adrenocorticotropic hormone (ACTH), cortisol, 4-androstenedione (ASD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 17-hydroxyprogesterone (17OHP), epinephrine (EPI), norepinephrine (NE), interleukin 6 (IL6), and tumour necrosis factor (TNF) were analysed in plasma.

Results: Patients had comparable responses of glucose, cortisol, ACTH, ASD, and 17OHP to hypoglycaemia, without any signs of hypothalamic insufficiency. Patients had lower basal DHEAS than controls (3.03 (0.37) µmol/l v 5.1 (0.9) µmol/l, respectively; p<0.05); borderline lower basal DHEA levels (p = 0.067); while the response of DHEA to hypoglycaemia was comparable to that of controls. Patients with RA had lower EPI (p = 0.005) and NE (p<0.001) responses to hypoglycaemia. TNF and IL6 were higher (p<0.05) in patients with RA (TNF 8 (2.8) pg/ml in RA v 1.1 (0.5) pg/ml in controls and IL6 15.1 (6.7) pg/ml v 1.4 (0.7) pg/ml).

Conclusions: Lower basal DHEAS levels, without concomitant differences or changes in DHEA, ASD, 17OHP, and cortisol responses to hypoglycaemia in patients with RA, indicate an isolated decrease in adrenal androgen production. Significantly lower responses of EPI and NE to hypoglycaemia may suggest sympathoadrenal hyporeactivity in patients with RA.

Abbreviations: ACTH, adrenocorticotropic hormone; ASD, 4-androstenedione; AUC, area under the curve; DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulphate; EPI, epinephrine; HPA, hypothalamic-pituitary-adrenal; 3ß-HSD, 3ß-hydroxysteroid dehydrogenase; IL, interleukin; 17OHP, 17-hydroxyprogesterone; NE, norepinephrine NSAIDs, non-steroidal anti-inflammatory drugs; RA, rheumatoid arthritis; SNS, sympathetic nervous system; TNF, tumour necrosis factor

Keywords: adrenal androgens; hypothalamic-pituitary-adrenal axis; sympathoadrenal system

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