Familial associations for Addison’s disease and between Addison’s disease and other autoimmune diseases

Abstract

Design: Addison disease (AD) is a rare autoimmune disease (AID) of the adrenal cortex, presenting as an isolated AD or part of autoimmune polyendocrine syndromes (APSs) 1 and 2. Although AD patients present with a number of AID co-morbidities, population-based family studies are scarce. We aimed to carry out an unbiased study on AD and related AIDs. Methods: We collected data on patients diagnosed with AIDs in Swedish hospitals, and calculated standardized incidence ratios (SIRs) in families for concordant AD and for other AIDs, the latter as discordant relative risks. Results: The number of AD patients was 2852, which accounted for 0.4% of all hospitalized AIDs. A total of 62 persons (3.6%) were diagnosed with familial AD. The SIR for siblings was remarkably high, reaching 909 for singleton siblings diagnosed before age 10 years. It was 32 in those diagnosed past age 29 years and the risk for twins was 323. SIR was 9.44 for offspring of affected parents. AD was associated with 11 other AIDs, including thyroid AIDs and type 1 diabetes, and some rarer AIDs such as Guillain-Barre syndrome, myasthenia gravis, polymyalgia rheumatica and Sjögren syndrome. Conclusions: The familial risk for AD was very high implicating genetic etiology, which for juvenile siblings may be ascribed to APS-1. The adult part of sibling risk was probably contributed to by recessive polygenic inheritance. AD was associated with many common AIDs; some of these were known co-morbidities in AD patients while some other appeared to more specific for a familial setting.

Genetic variants and risk of endocrine autoimmunity in relatives of patients with Addison’s disease

“…Recently, we and others have also confirmed increased risk for autoimmune disorders in families of patients with autoimmune adrenal insufficiency, i.e. Addison's disease (AD) (3,4). Patients suffering from AD display extreme predisposition to other autoimmune disorders and more than half of them present with additional autoimmune diseases (5)(6)(7).…”

“…However, most of the autoimmune endocrine diseases, including the majority of AD cases, display complex inheritance patterns. Furthermore, although less than 10% of AD patients have a relative with the same condition, various other endocrine diseases emerge in their family members (4,5,8).…”