Thyroid Hormone Resistance (Positive THRB Gene), Child Case Study

Introduction: Thyroid hormone resistance (RTHβ) is a rare disorder characterized by reduced tissue responsiveness to thyroid hormones (THs). It is primarily caused by mutations in the thyroid hormone receptor beta (THRB) gene. This case describes a two-year-old boy diagnosed with RTHβ following the incidental detection of elevated thyroid hormones during a routine checkup. The clinical presentation, laboratory findings, genetic analysis, and implications for management are discussed, highlighting the complexities of this rare condition. Patient concern and Clinical Finding: A two-year-old boy was referred to the Pediatric Endocrinology Department due to elevated FT4 and FT3 levels with normal TSH identified in routine blood tests. Born at 36 weeks after an uneventful pregnancy to non-consanguineous parents, the child had normal growth and development until subtle symptoms, such as reduced physical activity, weight loss despite adequate nutrition, and warm, sweaty skin, were observed. Physical examination showed no goiter or ophthalmopathy, with neurological development appropriate for age and weight and height within normal percentiles. Laboratory tests revealed elevated thyroid hormone levels, negative thyroid antibodies, and normal thyroid ultrasound findings. Diagnosis/Intervention/Outcomes: The diagnosis of resistance to thyroid hormone beta (RTHβ) was confirmed through whole exome sequencing, which identified a heterozygous missense mutation in the THRB gene (c.1313G>A; p.R438H). This de novo mutation ruled out inheritance and suggested a sporadic origin. Regular monitoring of thyroid function tests and clinical follow-ups ensured biochemical stability and vigilance for potential symptoms of thyroid dysfunction. The child remained clinically euthyroid with normal growth and development, showing peripheral adaptation to altered thyroid hormone signaling. Long-term surveillance was recommended to monitor for any late-onset complications or thyroid-related symptoms, with an overall favorable prognosis. Conclusion: This case illustrates the complexities of diagnosing and managing RTHβ in a pediatric patient. The identification of a THRB mutation provided a definitive diagnosis and emphasized the utility of genetic testing. Long-term follow-up is essential to monitor the clinical course and adjust management as needed. Further studies are required to elucidate the genotype-phenotype correlations in RTHβ and optimize treatment strategies.