Resistance to Thyroid Hormone due to THRB Mutation c.1057A > G (p.Ile353Val): A Rare Genetic Variant

Resistance to thyroid hormone (RTH) is a rare clinical syndrome caused by reduced tissue responsiveness to thyroid hormones. It is most commonly due to mutations in the thyroid hormone receptor β (THRB) gene and less frequently due to mutations in the thyroid hormone receptor α (THRA) gene. The clinical presentation is highly variable, ranging from asymptomatic individuals to patients with features of thyrotoxicosis—such as resting tachycardia, goiter, tremors, and advanced bone age—or occasionally symptoms suggestive of hypothyroidism, depending on tissue-specific receptor distribution. To date, more than 250 mutations associated with RTH have been described. We report a case of RTH caused by a heterozygous missense mutation in the THRB gene (c.1057A > G; p.Ile353Val). The patient presented with elevated thyroid hormone levels with a non-suppressed thyroid-stimulating hormone (TSH), consistent with thyroid hormone resistance. Early recognition of this condition is important to avoid misdiagnosis and unnecessary investigations, such as pituitary imaging for a suspected TSH-secreting pituitary adenoma, which represents a key differential diagnosis in patients with elevated thyroid hormone levels and an inappropriately normal or elevated TSH.