Autoimmune Addison's disease (AAD) is a rare and debilitating disease in which an autoimmune attack progressively destroys the adrenal cortex. Untreated it is universally fatal and treated people are absolutely dependent upon steroid medications lifelong, with a consequent excess in morbidity and mortality. A key feature of the adrenal cortex is that its cells are responsive to changes in circulating adrenocorticotrophic hormone (ACTH) concentration. This study aims to regenerate adrenocortical steroidogenic cell function in patients with established autoimmune Addison's disease (AAD) by stimulating proliferation and differentiation of their progenitor cells, the adrenocortical stem cells (ACSCs) (1,2). Using daily subcutaneous ACTH, administered according to two different regimens over 20 weeks, we will investigate whether regeneration of adrenal steroidogenic function through revival of ACSC activity is a realistic possibility.

Inclusion Criteria:

• Established autoimmune adrenal failure for >1yr age 16 to 65

Exclusion Criteria:

• Significant cardio-respiratory, chronic renal or non-autoimmune liver disease; malignancy
• Asthma, current infectious disease, recent live vaccination, acute psychosis, peptic ulcer disease
• Pregnancy, breast feeding or plan for pregnancy within 9 months
• Known non-autoimmune cause for adrenal failure (haemorrhage, adrenoleukodystrophy etc.)
• Known hypersensitivity or allergy to Synacthen