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Residual Adrenal Function in Autoimmune Addison's Disease: Improvement After Tetracosactide (ACTH1-24) Treatment

Lookup NU author(s): Dr Earn Gan, Katie MacArthur, Dr Anna Mitchell, Dr Petros Perros, Dr Stephen Ball, Dr Richard Quinton, Professor Simon Pearce

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Abstract

Context: Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. Objective: We aimed to determine whether tetracosactide (synthetic ACTH(1-24)) could revive adrenal steroidogenic function in autoimmune Addison's disease. Design, Setting, and Patients: Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. Intervention: The intervention included a 20-week study of regular sc tetracosactide (ACTH(1-24)) therapy. Main Outcome Measures: Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Results: Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement. Conclusion: This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.


Publication metadata

Author(s): Gan EH, MacArthur K, Mitchell AL, Hughes BA, Perros P, Ball SG, James RA, Quinton R, Chen S, Furmaniak J, Arlt W, Pearce SHS

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology and Metabolism

Year: 2014

Volume: 99

Issue: 1

Pages: 111-118

Print publication date: 01/01/2014

Online publication date: 29/10/2013

Acceptance date: 16/10/2013

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: Endocrine Society

URL: http://dx.doi.org/10.1210/jc.2013-2449

DOI: 10.1210/jc.2013-2449


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