Residual Adrenal Function in Autoimmune Addison's Disease - Effect of Dual Therapy with Rituximab and Depot Tetracosactide.

Napier, Catherine and Gan, Earn H and Mitchell, Anna L and Gilligan, Lorna C and Rees, D Aled and Moran, Carla and Chatterjee, Krishna and Vaidya, Bijay and James, R Andrew and Mamoojee, Yaasir and Ashwell, Simon and 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 (Unpublished)

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Official URL: https://academic.oup.com/jcem/advance-article/doi/...

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
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
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Depositing User: Mr Muneeb Liaquat
Date Deposited: 02 Jan 2020 10:08
Last Modified: 02 Jan 2020 10:08
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2725

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