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Adrenal Steroidogenesis after B Lymphocyte Depletion Therapy in New-Onset Addison's Disease

Lookup NU author(s): Professor Simon PearceORCiD, Dr Anna MitchellORCiD, Dr Stuart Bennett, Professor John IsaacsORCiD, Dr Bijayeswar Vaidya


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Context: 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. Objective: The objective of the study was to determine whether immunomodulatory therapy at an early stage of autoimmune Addison's disease could lead to preservation or improvement in adrenal steroidogenesis. Design and Intervention: This was an open-label, pilot study of B lymphocyte depletion therapy in new-onset idiopathic primary adrenal failure. Doses of iv rituximab (1 g) were given on d 1 and 15, after pretreatment with 125 mg iv methylprednisolone. Patients and Main Outcome Measures: Six patients (aged 17-47 yr; four females) were treated within 4wk of the first diagnosis of idiopathic primary adrenal failure. Dynamic testing of adrenal function was performed every 3 months for at least 12 months. Results: Serum cortisol levels declined rapidly and were less than 100 nmol/liter (3.6 mu g/dl) in all patients by 3 months after B lymphocyte depletion. Serum cortisol and aldosterone concentrations remained low in five of the six patients throughout the follow-up period. However, a single patient had sustained improvement in both serum cortisol [peak 434 nmol/liter (15.7 mu g/dl)] and aldosterone [peak 434 pmol/liter (15.7 ng/dl)] secretion. This patient was able to discontinue steroid medications 15 months after therapy and remains well, with improving serum cortisol levels 27 months after therapy. Conclusion: New-onset autoimmune Addison's disease should be considered as a potentially reversible condition in some patients. Future studies of immunomodulation in autoimmune Addison's disease may be warranted. (J Clin Endocrinol Metab 97: E1927-E1932, 2012)

Publication metadata

Author(s): Pearce SHS, Mitchell AL, Bennett S, King P, Chandran S, Nag S, Chen S, Smith BR, Isaacs JD, Vaidya B

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology and Metabolism

Year: 2012

Volume: 97

Issue: 10

Pages: E1927-E1932

Print publication date: 05/07/2012

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: The Endocrine Society


DOI: 10.1210/jc.2012-1680


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Funder referenceFunder name
G07017632Medical Research Council, Experimental Medicine-2 panel, United Kingdom