Endocrine Abstracts (2012) 28 OC3.5

Steroidogenic function following B lymphocyte depletion therapy in new onset autoimmune Addison's disease

Simon Pearce1, Anna Mitchell1, Stuart Bennett2, Philip King2, Sukesh Chandran3, Sath Nag4, Shu Chen5, Jadwiga Furmaniak5, John Isaacs6 & Bijay Vaidya7


1Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; 2Department of Diabetes and Endocrinology, North Tyneside General Hospital, Newcastle upon Tyne, United Kingdom; 3Department of Diabetes and Endocrinology, Bishop Auckland General Hospital, Co. Durham, United Kingdom; 4Department of Diabetes and Endocrinology, James Cook University Hospital, Middlesbrough, United Kingdom; 5FIRS Laboratories, RSR limited, Cardiff, United Kingdom; 6Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; 7Macleod Diabetes and Endocrinology Centre, Royal Devon and Exeter Hospital, Exeter, United Kingdom.


Background: A diagnosis of Addison’s 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 Addison’s 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 Addison’s disease should be considered as a potentially reversible condition in some patients. Future studies using immunomodulatory approaches in autoimmune Addison’s 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.

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