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Residual adrenal function in autoimmune addison's disease - effect of dual therapy with rituximab and depot tetracosactide

Napier, Catherine, Gan, Earn H, Mitchell, Anna L, Gilligan, Lorna C, Rees, D. Aled, Moran, Carla, Chatterjee, Krishna, Vaidya, Bijay, James, R Andrew, Mamoojee, Yaasir, Ashwell, Simon, Arlt, Wiebke and Pearce, Simon HS 2019. Residual adrenal function in autoimmune addison's disease - effect of dual therapy with rituximab and depot tetracosactide. Journal of Clinical Endocrinology and Metabolism 10.1210/clinem/dgz287
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Abstract

Context In autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion. Patients on long-term steroid replacement have increased morbidity, reduced life expectancy and poorer quality of life. Objective To restore adrenocortical steroidogenic function in recent onset AAD. Design Open-label, multi-centre trial of immunotherapy and trophic stimulation in new-onset AAD. Serial measurement of serum and urine corticosteroids at baseline and throughout 72-week follow-up period. Setting Endocrine Departments and Clinical Research Facilities at 5 UK tertiary centres. Patients Thirteen subjects (9 female, 4 male; aged 19-64 years) with AAD confirmed by high ACTH, low circulating cortisol (basal <100nmol/L or post-tetracosactide <300nmol/L) and positive serum 21-hydroxylase antibodies. Intervention All subjects received dual therapy with B-lymphocyte depleting immunotherapy (rituximab 1g given twice) and repeated depot tetracosactide (1mg alternate days for 12 weeks). Main Outcome Measure Restoration of normal glucocorticoid secretion (stimulated cortisol >550nmol/L) at Week 48. Results Ten of 13 (77%) had detectable stimulated serum cortisol (26-265nmol/L) at trial entry. Following intervention, 7/13 (54%) had an increase in stimulated cortisol measurement, with a peak response of 325nmol/L at Week 18 in one subject. Increased steroid metabolites, assayed by urine GC-MS at Week 12 and Week 48, was detected in 8/13 (62%), reflecting an increase in endogenous steroidogenesis. Four of 13 had Residual Adrenal Function at 72 weeks. Conclusion Combined treatment with rituximab and depot tetracosactide did not restore normal adrenal function. Nevertheless, adrenocortical plasticity is demonstrated in some patients and this has the potential to be exploited to improve adrenal function.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Oxford University Press
ISSN: 0021-972X
Date of First Compliant Deposit: 8 January 2020
Date of Acceptance: 13 December 2019
Last Modified: 10 Mar 2020 16:45
URI: http://orca.cf.ac.uk/id/eprint/128360

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