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Background: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD)., Methods: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined., Results: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases., Conclusions: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions., (© 2021. The Author(s).)

Background: Graves' disease (GD) is commonly associated with other autoimmune conditions, and there is also a rare but well documented association between GD and thymic hyperplasia (TH). It is hard to say the real frequency of this latter association because most cases remain asymptomatic and are consequently not thoroughly investigated., Materials and Methods: We reviewed the literature on GD-related thymus enlargement and found 107 cases published to date. Thymic cancer was only documented in four patients, while the majority of cases were diagnosed as TH. The causative mechanisms behind TH associated with GD have yet to be fully elucidated. Several studies support the hypothesis of a TSH receptor antibody (TRAb) mediating thymic enlargement., Results: We report on a female GD patient with an incidentally discovered anterior mediastinal mass. Our case is not consistent with the hypothesis of a TRAb-mediated mechanism because the thymus reached its largest volume at the onset of GD and shrank during remission of GD under medical treatment, despite persistently positive TRAb levels., Conclusion: We support the hypothesis that two different pathogenic mechanisms might be responsible for thymus enlargement: thymic cortical tissue expansion seems to be due to a hyperthyroid state, while lymphoid hyperplasia appears to correlate with immune abnormalities underlying GD.