SFEBES2013 Poster Presentations Steroids (37 abstracts)
Revival of adrenal function in established autoimmune Addison's disease
Earn H Gan 1, , Anna L Mitchell 1, , Petros Perros 1 , Andy James 1 , Steve Ball 1, , Jadwiga Furmaniak 3 , Shu Chen 3 , Richard Quinton 1, & Simon HS Pearce 1,
1Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, UK; 2Endocrine Unit, Royal Victoria Infirmary, Newcastle Upon Tyne, UK; 3FIRS Laboratories, RSR Ltd, Cardiff, UK.
Despite lifelong glucocorticoid and mineralocorticoid replacement, there is excess morbidity and mortality associated with autoimmune Addison’s disease (AAD). Adrenal cortical cells undergo continuous self-renewal from a population of subcapsular progenitor or stem cells, under the influence of ACTH. We aimed to determine if synthetic ACTH analogue could revive adrenal steroidogenic function and ameliorate AAD.
We performed an open-label trial of synthetic ACTH1–24 analogue (synacthen) in adults with established AAD for more than 1 year (NCT 01371526). In phase I, depot synacthen 1 mg was administered s.c. alternate days for 10 weeks. In phase II, participants were then randomised to a further 10 weeks of either a continuous 24 h infusion, or overnight 12 h pulsatile synacthen (both administered at 10 μg/h). Dynamic testing of adrenal function was performed every 5 weeks following medication withdrawal. Twelve subjects (aged 16–65; 11 females), were treated for either 10 (n=2) or 20 weeks (n=10). One participant withdrew after 5 weeks.
Serum cortisol and aldosterone levels remained under 100 nmol/l in 10 of 12 participants throughout the study. However, two participants both with detectable baseline serum cortisol (219 and 179 nmol/l) achieved peak serum cortisol concentrations >400 nmol/l, after 10 and 29 weeks of synacthen therapy, respectively; allowing withdrawal of replacement medication. These patients (both female, with positive 21-hydroxylase antibodies) had AAD for 8 and 4 years respectively. One of them remains well with improving serum cortisol levels 72 weeks after stopping all treatments. The other participant had a gradual reduction in both serum cortisol and aldosterone concentration, hence steroid therapy was recommenced at week-64.
This is the first study to demonstrate that established AAD may be amenable to a regenerative medicine therapy. We have also shown that AAD is a heterogeneous condition in terms of residual adrenal function, and that adrenal progenitor/stem cells may remain dormant for many years.
Declaration of funding: This work was supported by the Medical Research Council (grant number G0900001).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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