Variable phenotype associated with Ser505Asn-activating thyrotropin-receptor germline mutation

Constitutively activating thyrotropin-receptor (TSHR) germline mutations ha ve been identified as a molecular cause of hereditary nonautoimmune hyperth yroidism. To date, seven cases of familial and six cases of sporadic nonaut oimmune hyperthyroidism have been described associated with 13 different TS HR germline mutations, with a variable clinical course. We report the case of a 12.3-year-old girl with a history of thyrotoxicosis since the age of 1 1 months who developed diffuse thyroid hyperplasia at the age of 4.5 years. The patient has required continuous moderate-dose antithyroid medication, to maintain euthyroidism. There were no clinical signs of autoimmune thyroi d disease and autoantibodies were negative. An activating germline mutation in the TSHR gene was suspected and was found in TSHR exon 10 (Ser505Asn) b ut was absent in the girl's mother. This same mutation, was first reported in a patient with severe intrauterine hyperthyroidism with early and progre ssive goiter development. Our patient had a significantly less severe clini cal course with later onset compared to the original patient with the same TSHR germline mutation.