Clinical Characteristics and Genotype-Phenotype Correlation in the Patients with the Diagnosis of Resistance to Thyroid Hormone Beta.

Objective: Resistance to thyroid hormone beta (RTHβ) is a rare disorder characterized by a fairly heterogeneous clinical presentation due to varying degrees of tissue response to thyroid hormone. The study aimed to evaluate the clinical, laboratory features and genotype-phenotype relationship of Turkish patients with RTHβ.

Methods: Patients who underwent a THRB gene analysis between September 2019 and September 2023 were retrospectively reviewed.

Results: 50 patients with the clinical features of RTHβ syndrome or a family history of an index case were included. A total of 8 different heterozygous pathogenic/likely pathogenic missense variants (3 novel) were detected in the THRB gene in 30 patients from 8 unrelated families. Although most patients with RTHβ were asymptomatic, 7 patients had various symptoms. Seven patients had received various treatments before diagnosis. Thyroid autoantibody was positive in 23% of all cases with a variant, and goitre was detected in 56% of children with a variant. While thyroid nodules were detected in 7 adult patients, two adult patients were being followed with papillary thyroid cancer. One child patient had attention-deficit disorder, learning disability, and type 1 diabetes mellitus. Of the 20 patients without a variant, TSHoma was detected in one.

Conclusion: The present study, provides an overview of clinical and genetic characteristics of patients with genetically confirmed RTHβ and expanded the THRB gene variant database with 3 novel variants. Although most patients with RTHβ are asymptomatic, molecular genetics analysis of the THRB gene and regular follow-up for potential concurrent autoimmune diseases and thyroid cancer is warranted.