Abstract
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, Δ4-androstenedione (ASD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 17α-hydroxyprogesterone (17OHP), epinephrine (EPI), norepinephrine (NE), interleukin 6 (IL6), and tumour necrosis factor α (TNFα) 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. TNFα and IL6 were higher (p<0.05) in patients with RA (TNFα 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.
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Figure 1.
Concentrations of glucose, adrenocorticotropic hormone (ACTH), and cortisol in plasma of 15 patients with RA and 14 healthy controls during insulin-induced hypoglycaemia; the ACTH data were measured in 12 patients with RA and 11 healthy controls. Data are means, error bars = SEM. Inserts in graph panels indicate values of areas under the response curve (AUCs) of ACTH from 0 to 90 minutes and AUCs of cortisol from 0 to 60 minutes in patients with RA and healthy controls.
Figure 2.
Concentrations of 17α-hydroxyprogesterone, Δ4-androstenedione, and dehydroepiandrosterone in plasma of 15 patients with RA and 14 healthy controls during insulin-induced hypoglycaemia. Data are means, error bars = SEM. Inserts in graph panels indicate values of areas under response curve (AUCs) of respective hormones from 0 to 90 or 0–60 minutes in patients with RA and healthy controls.
Figure 3.
Concentrations of epinephrine and norepinephrine in plasma of 12 patients with RA and 11 healthy controls during insulin-induced hypoglycaemia. Data are means, error bars = SEM. Inserts in graph panels indicate significantly lower values of areas under response curve (AUCs) of both epinephrine and norepinephrine from 0 to 60 minutes in patients with RA compared healthy controls at p<0.05. Asterisks indicate the level of statistical significance between patients with RA and healthy controls assessed by two way analysis of variance for repeated measurements (**p = 0.005, ***p<0.001).
Figure 4.
Scattergram and linear regression lines of areas under the response curve (AUC) of ACTH from 0 to 45 minutes (ACTH AUC 0-45) v AUC of cortisol from 0 to 60 minutes (CORT AUC 0-60) in 12 patients with RA (r2 = 0.019) and 11 healthy controls (r2 = 0.094) indicating comparable HPA function during insulin-induced hypoglycaemia.
Selected References
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