SUN-366 Resistance to Thyroid Hormone Beta in Two Siblings: A Case Report

Abstract Disclosure: H. Jeong: None. Background: Resistance to thyroid hormone (RTH) beta is a rare genetic condition caused by mutations in the thyroid hormone receptor beta (THRβ) gene, leading to elevated thyroid hormone levels with non-suppressed TSH and variable clinical manifestations.Case Presentation: We describe two siblings diagnosed with RTH beta, confirmed by a heterozygous THRβ mutation (c.1357C>A, p.Pro453Thr).Case 1: A 1-year-and-6-month-old boy presented with delayed language development, increased physical activity, and tachycardia. Initial thyroid function tests revealed elevated T3 (3.14 ng/mL) and FT4 (3.59 ng/dL) with normal TSH (3.96 μIU/mL). Methimazole therapy failed to normalize thyroid hormone levels, and genetic testing confirmed RTH beta. The patient was subsequently managed with propranolol for symptomatic relief.Case 2: The younger sister, a newborn, presented with jaundice and dehydration. Initial thyroid function tests revealed elevated FT4 (3.63 ng/dL) and TSH (25.8 μIU/mL). Over time, her growth percentiles declined, and persistent tachycardia was managed with propranolol and T3 supplementation. Genetic testing confirmed the same mutation as her older brother. The siblings’ mother, diagnosed with hyperthyroidism at 13 years old, was presumed to carry the same mutation, indicating maternal inheritance. Conclusion: These cases highlight the clinical variability of RTH beta and the challenges in management, including persistent symptoms despite conventional therapy. Genetic testing is crucial for early diagnosis and individualized treatment, especially in patients with a family history of thyroid dysfunction. Long-term monitoring is essential to address growth and developmental concerns in pediatric RTH beta patients. Presentation: Sunday, July 13, 2025