Background: A diagnosis of Addisons disease means lifelong dependence on daily glucocorticoid and mineralocorticoid therapy and is associated with increased morbidity and mortality, as well as a risk of unexpected adrenal crisis. We wished to explore whether immunomodulatory therapy at an early stage of autoimmune Addisons disease could lead to preservation or improvement in adrenal steroidogenic function.
Design: We conducted an open-label, pilot study of B lymphocyte depletion therapy (registered as NCT00753597) in six patients (age 17 47 yr; 4F), who were treated within 4 weeks of the first diagnosis of idiopathic primary adrenal failure. Doses of IV rituximab (1 g) were given on days 1 and 15, after pre-treatment with 125 mg IV methylprednisolone. Dynamic testing of adrenal function was performed 3 monthly for at least 12 months, including peak serum cortisol response to tetracosactrin, aldosterone, DHEAS, plasma ACTH and renin activity (after 36 hr in-patient medication withdrawal).
Results: Antibodies to steroid 21-hydroxylase were positive at baseline in 5 of 6 patients and declined to less than 50% of baseline in 3 of the 5 (P=0.03 for change from baseline in all 6 subjects). Serum cortisol levels declined rapidly and were less than 100 nmol/l in all patients by 3 months following B lymphocyte depletion. Peak serum cortisol and aldosterone concentrations remained low in five out of the 6 patients throughout the follow up period. However, a single patient had sustained improvement in steroidogenesis, including both serum cortisol (peak 431 nmol/l) and aldosterone (peak 434 pmol/l) secretion. This patient was able to discontinue steroid medications 15 months after therapy and remains well, with improving serum cortisol levels at 21 months post therapy.
Comment: New onset autoimmune Addisons disease should be considered as a potentially reversible condition in some patients. Future studies using immunomodulatory approaches in autoimmune Addisons disease are warranted.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.