Background Glucocorticoids are widely used to treat a variety of diseases, including systemic autoimmune disease. Although glucocorticoids can improve the outcome for patients with these diseases, various side effects, such as suppression of the hypothalamic-pituitary-adrenal (HPA) axis are important problems. On the other hand, pro-inflammatory cytokines, such as IL-6 have been reported as stimulators of HPA axis in patients with systemic autoimmune diseases [1]. However, the influence of glucocorticoid therapy on HPA axis of inflammatory diseases has not be studied yet.

Objectives The aim of this study is to examine the process of suppression of HPA axis after glucocorticoid therapy using CRH test in patients with systemic autoimmune diseases.

Methods Thirty-five patients with systemic autoimmune diseases (64.4±16.1 y.o., M±SD), including 5 patients with systemic lupus erythematosus, 6 patients with polymyositis/dermatomyositis, 4 patients with vasculitis syndrome, 10 patients with polymyalgia rheumatica, 3 patients with rheumatoid arthritis, and 7 patients with other systemic autoimmune diseases, who received initial glucocorticoid therapy were gave written informed consent and enrolled. HPA axis was assessed by plasma adrenocorticotropin (ACTH) and serum cortisol levels of pre-CRH treatment, 30 and 60 minutes after administration of 100 μg of exogenous human CRH, and that was performed at 0, 2, and 4 weeks after starting glucocorticoid therapy. Patients were divided into two groups with prednisolone daily dose: 30 mg or more (18 patients, high-dose group), and 15mg or less (17 patients, low-dose group). The basal concentrations of plasma ACTH and serum cortisol, and their increased values after CRH stimulation (ΔACTH and Δcortisol, respectively) were evaluated. C-reactive protein (CRP) was also measured. This study was approved by the Ethics Committee at Toho University Omori Medical Center (approval no.25-215).

Results As shown in Table1, basal ACTH and ΔACTH levels were significantly decreased after glucocorticoid therapy in the high-dose group, while those in the low-dose group were not suppressed. Basal cortisol levels in high and low dose groups were significantly suppressed by glucocorticoid therapy. Δcortisol level in high dose group was significantly suppressed, however, that in low dose group had a trend to decrease. CRP was significantly decreased after glucocorticoid therapy in both groups.

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Conclusions In the low-dose group, the pituitary function was not suppressed by glucocorticoid therapy, however, the adrenal function was significantly suppressed. It is suggested that adrenal suppression by glucocorticoid therapy might be caused not only by feedback regulation via pituitary suppression, but also suppression of systemic inflammation, as possible activating factors of adrenal function, in patients with systemic autoimmune diseases.

References

1. Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab. 1993 Dec;77(6):1690-4.

Disclosure of Interest None declared