Thomsen Hauke, Li Xinjun, Sundquist Kristina, Sundquist Jan, Försti Asta, Hemminki Kari
Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Center for Primary Health Care Research, Lund University, Malmö, Sweden.
Endocr Connect. 2020 Nov;9(11):1114-1120. doi: 10.1530/EC-20-0328.
Addison's disease (AD) is a rare autoimmune disease (AID) of the adrenal cortex, present 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, and we aimed to carry out an unbiased study on AD and related AIDs.
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.
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's syndrome.
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 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.
艾迪生病（AD）是一种罕见的肾上腺皮质自身免疫性疾病（AID），可表现为孤立性AD或自身免疫性多内分泌综合征（APS）1型和2型的一部分。尽管AD患者存在多种AID合并症，但基于人群的家族研究较少，我们旨在对AD及相关AID进行无偏倚研究。
我们收集了瑞典医院中被诊断为AID的患者数据，并计算了家族中AD及其他AID的标准化发病率（SIR），后者作为不一致的相对风险。
AD患者有2852例，占所有住院AID患者的0.4%。共有62人（3.6%）被诊断为家族性AD。兄弟姐妹的SIR非常高，10岁前被诊断的单胎兄弟姐妹高达909。29岁以后被诊断的为32，双胞胎的风险为323。受影响父母的后代SIR为9.44。AD与其他11种AID相关，包括甲状腺AID和1型糖尿病以及一些罕见的AID，如格林-巴利综合征、重症肌无力、风湿性多肌痛和干燥综合征。
AD的家族风险非常高，提示遗传病因，对于青少年兄弟姐妹可能归因于APS-1。兄弟姐妹风险的成人部分可能由隐性多基因遗传导致。AD与许多常见的AID相关；其中一些是AD患者已知的合并症，而其他一些似乎在家族背景中更具特异性。
