BSPED2014 Main Symposia Symposia 2 Recent advances in adrenal disease (2 abstracts)
Newcastle University, Newcastle, UK.
Addisons disease is a good therapeutic target for regenerative medicine, as adrenal cell mass and steroidogenesis have clear intrinsic plasticity, as determined by circulating ACTH concentrations. With the advent of the biological agents as disease-modifying therapy for inflammatory arthritis and their experimental use in several other autoimmune conditions including type 1 diabetes, we undertook a pilot study of immunomodulatory therapy in patients with autoimmune Addisons disease. Six newly diagnosed patients were treated with B cell depletion, leading to a drop in serum 21-hydroxylase antibodies in all and one patient had a progressive rise in serum cortisol, such that she was able to discontinue steroid replacement. In a further attempt to explore the plasticity of adrenal steroidogenesis in Addisons disease, we performed a 20-week study of high dose ACTH124 (Synacthen) therapy in 13 patients with established autoimmune Addisons disease. Two of the 13 patients had significant residual adrenal function at baseline, and both had progressive rises in serum cortisol and aldosterone during ACTH therapy. Both were able to stop oral glucocorticoid and mineralocorticoid replacement during the study, but one of the patients had a progressive decline in steroidogenic function once ACTH was discontinued. The other patient remains well with good steroidogenic function and no replacement medications 36 months after ACTH was stopped. These studies highlight that residual adrenal function in patients with Addisons disease is important as a future therapeutic target, and starts to explain why spontaneous recovery of established Addisons disease has occasionally been reported.