The natural history of 21-hydroxylase autoantibodies in autoimmune Addison’s disease

Abstract

Background The most common cause of primary adrenal failure (Addison’s disease) in the Western world is autoimmunity characterized by autoantibodies against the steroidogenic enzyme 21-hydroxylase (CYP21A2, 21OH). Detection of 21OH-autoantibodies is currently used for aetiological diagnosis, but how levels of 21OH-autoantibodies vary over time is not known. Setting Samples from the national Norwegian Addison’s Registry and Biobank established in 1996 (n = 711). Multi-parameter modelling of the course of 21OH-autoantibody indices over time. Results 21OH-autoantibody positivity is remarkably stable, and >90% of the patients are still positive 30 years after diagnosis. Even though the antibody levels decline with disease duration, it is only rarely that this downturn reaches negativity. 21OH-autoantibody indices are affected by age at diagnosis, sex, type of Addison’s disease (isolated vs autoimmune polyendocrine syndrome type I or II) and HLA genotype. Conclusion 21OH-autoantibodies are reliable and robust markers for autoimmune Addison’s disease, linked to HLA risk genotype. However, a negative test in patients with long disease duration does not exclude autoimmune aetiology.