SFEBES2018 Oral Communications Adrenal (6 abstracts)
Residual adrenal function in autoimmune addison s disease effect of dual therapy with rituximab and depot tetracosactide
Catherine Napier 1, , Earn H Gan 1, , Anna L Mitchell 1, , Lorna C Gilligan 3 , Aled Rees 4 , Carla Moran 5 , Krishna Chatterjee 5 , Bijay Vaidya 6 , Wiebke Arlt 3 & Simon HS Pearce 1,
1Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; 2Newcastle upon Tyne Hospitals, Newcastle Upon Tyne, UK; 3University of Birmingham, Birmingham, UK; 4Cardiff University, Cardiff, UK; 5University of Cambridge, Cambridge, UK; 6University of Exeter, Exeter, UK.
In patients with 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. Recent early-phase studieshave demonstrated that some endogenous steroidogenic function – Residual Adrenal Function (RAF) - is maintained at the point of diagnosis in a proportion of AAD patients; this can be harnessed and exploited with novel therapies. The RADS2 (rescue of addison’s disease 2) study examined the impact of B-lymphocyte depleting immunotherapy and trophic stimulation on steroidogenic function in AAD for the first time. Dual therapy with rituximab and depot tetracosactide was administered in 13 subjects (9 female, 4 male; aged 19–64 years) with new onset AAD within 4 weeks. A detailed assessment of serum and urine GC, mineralocorticoids (MC) and androgens was performed at baseline and at regular intervals throughout the 72-week follow-up period (during temporary cessation of exogenous steroid replacement). 10/13 (77%) subjects had evidence of RAF on trial entry (detectable cortisol on short synacthen testing (SST); range 26-265 nmol/L). Following intervention, 7/13 (54%) subjects had an increase in stimulated cortisol measurement, with a peak response of 325 nmol/l at Week 18 in 1 patient, which facilitated weaning of exogenous GC replacement to hydrocortisone 5mg daily. Increased urinary excretion of steroid metabolites, assayed by GC-MS at baseline, Week 12 and Week 48, was detected in 8/13 (62%) subjects post-intervention, reflecting an increase in endogenous adrenal steroidogenesis. While combined treatment with rituximab and depot tetracosactide did not restore normal adrenal function, this study shows that adrenocortical plasticity can be exploited post-diagnosis to improve endogenous steroid secretion. Future considerations should include exploring the utility of an alternative immunotherapeutic regimen, alongside newer regenerative medicine approaches, with the aim of improving patient outcomes for those with AAD.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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