Increased Risk of Autoimmune Disorders in 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study

Context The prevalence of autoimmune disorders in individuals with 21-hydroxylase deficiency (21OHD) is unclear. The gene responsible, CYP21A2, is located in a highly immunologically active region. Objective To study the prevalence of autoimmune disorders in individuals with 21OHD. Design, Setting, and Participants Patients with 21OHD (n = 714) were compared with controls matched for sex, year, and place of birth (n = 71,400). Data were derived by linking National Population-Based Registers. Subgroup analyses were performed regarding phenotype and CYP21A2 genotype. Main Outcome Measures Number and type of autoimmune disorders. Results Mean age (± SD) was 29.8 ± 18.4 years. Individuals with 21OHD had more autoimmune disorders than did controls [7.4% vs 5.1%, P < 0.01; relative risk (RR) 1.47 (95% CI, 1.13 to 1.91)], especially male patients [6.8% vs 4.1%, P < 0.05; RR, 1.64 (95% CI, 1.08 to 2.49)], whereas it did not reach significance for female patients [7.9% vs 5.8%, P = 0.068; RR, 1.37 (95% CI, 0.98 to 1.92)]. Among the specific autoimmune groups and disorders, autoimmune endocrine disorders and autoimmune thyroid disorders, including Graves disease, were significantly increased in the entire cohort of patients and for male and female patients separately. Inflammatory bowel disease (IBD) and systemic connective tissue disorders did not reach significant levels for the entire cohort (P = 0.075 and 0.05, respectively), but male patients were more affected by IBD (P = 0.022). The groups with milder phenotypes and genotypes seemed to be more affected by autoimmune disorders. Conclusions 21OHD was associated with an increased prevalence of autoimmune disorders. The relatively young age of the patient cohort and possible protective effects by glucocorticoid treatment may have underestimated the risk.