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. The Journal of clinical endocrinology and metabolism. ISSN 1945-7197. (Unpublished)

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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.


To restore adrenocortical steroidogenic function in recent onset AAD.


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.


Endocrine Departments and Clinical Research Facilities at 5 UK tertiary centres.


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.


All subjects received dual therapy with B-lymphocyte depleting immunotherapy (rituximab 1g given twice) and repeated depot tetracosactide (1mg alternate days for 12 weeks).


Restoration of normal glucocorticoid secretion (stimulated cortisol >550nmol/L) at Week 48.


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.


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
Subjects: QW Microbiology. Immunology
WK Endocrine system. Endocrinology
Divisions: Ambulatory Care > Diabetes
Ambulatory Care > Theatres
Planned IP Care > Gastroentrology
Planned IP Care > Oncology and Clinical Haematology
Related URLs:
Depositing User: Mr Muneeb Liaquat
Date Deposited: 02 Jan 2020 10:08
Last Modified: 02 Jan 2020 10:08

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