Non-autoimmune Familial Hyperthyroidism in Children: The Importance of Genetic Testing

Hyperthyroidism of non-autoimmune etiology is an uncommon occurrence, and its etiology may be the result of germline variants capable of activating the thyroid-stimulating hormone receptor (TSHR). The case of a 16-year-old adolescent with a family history of hyperthyroidism and negative antithyroid antibodies is presented. Imaging revealed bilateral subcentimeter nodules, and thyroid scintigraphy showed normal, heterogeneous uptake, with no hyperfunctioning areas. Genetic testing identified the likely pathogenic variant c.2009A>G p.(Asn670Ser) in the TSHR gene, which has been previously described in families with non-autoimmune hyperthyroidism. The patient is undergoing treatment with methimazole, with normalization of thyroid function and clinical surveillance. This case highlights the need to consider alternative etiologies of hyperthyroidism, particularly in the absence of autoimmune markers and in the presence of a strong family history, reinforcing the role of genetic testing in this clinical context.