Pituitary-Adrenal Function After Prolonged Glucocorticoid Therapy for Systemic Inflammatory Disorders: An Observational Study

Abstract

Glucocorticoid therapy is being used in a wide variety of systemic disorders. Reference papers, published more than 20 years ago, showed no correlation between adrenal insufficiency risk and dose or duration of glucocorticoid therapy. Our objective was to evaluate the extent to which long-term glucocorticoid therapy damages the pituitary-adrenal axis in patients with systemic inflammatory disorders. We conducted a retrospective observational study from January 2011 to August 2012. This was a monocentric study at the Department of Internal Medicine, Bichat Hospital, Paris-Diderot University, Paris, France. Sixty consecutive patients who were receiving long-term prednisone therapy for systemic inflammatory disorders and in whom discontinuation of glucocorticoid treatment was planned. A short Synacthen test was performed. A bolus of 0.25 mg 1-24-ACTH was injected in the morning, 24 hours after the most recent dose of prednisone. Cortisol was measured at baseline and 60 minutes after Synacthen injection. We assessed frequency and risk estimate of pituitary-adrenal dysfunction. Twenty-nine patients (48.3%) had adrenal insufficiency defined by a plasmatic cortisol <100 nmol/L (n = 13) at baseline (time 0) or <550 nmol/L (n = 16) 60 minutes after Synacthen injection. Cumulative dose (area under the receiver operating characteristic curve = 0.77 [95% confidence interval = 0.62-0.91], P = .007) and exposure (area under the receiver operating characteristic curve 0.80 [95% confidence interval = 0.67-0.93], P = .002) to prednisone were predictive for adrenal insufficiency based on a T0 <100 nmol/L. Prednisone was stopped in 29 of 31 patients (93.5%) showing a normal response to short Synacthen test; none of these patients required hydrocortisone replacement with a mean follow-up of 10 (± 6) months. Adrenal insufficiency is frequent in patients treated with long-term glucocorticoids for systemic inflammatory disorders and is related to duration and cumulative dose of steroids.