Evaluation of clinical characteristics and genotype-phenotype correlation of resistance to thyroid hormone receptor Beta (RTHβ) due to THRβ gene mutations

Gonul Gulal; Cavdarlı Busra Erozan; Koca Serkan Bilge; Adiguzel Keziban Toksoy; Oya Topaloglu; Cevdet Aydin; Sema Hepsen; Erman Cakal; Gunduz Nur Semerci; Mehmet Boyraz; Fatih Gurbuz; Huseyin Demirbilek

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ESPE Abstracts (2024) 98 P2-402

ESPE2024 Poster Category 2 Late Breaking (107 abstracts)

Evaluation of clinical characteristics and genotype-phenotype correlation of resistance to thyroid hormone receptor Beta (RTHβ) due to THRβ gene mutations

Gonul Gulal ¹ , Busra Erozan Cavdarlı ² , Serkan Bilge Koca ³ , Keziban Toksoy Adiguzel ¹ , Oya Topaloglu ⁴ , Cevdet Aydin ⁴ , Sema Hepsen ⁵ , Erman Cakal ⁵ , Nur Semerci Gunduz ⁶ , Mehmet Boyraz ⁷ , Fatih Gurbuz ⁷ & Huseyin Demirbilek ⁸

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¹Department of Pediatric Endocrinology, Ankara Bilkent City Hospital, Ankara, Turkey. ²Department of Medical Genetics, Ankara City Hospital, Ankara, Turkey. ³Health Sciences University, Kayseri City Hospital, Department of Pediatrics, Division of Pediatric Endocrinology, Kayseri, Turkey. ⁴Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey. ⁵Department of Endocrinology and Metabolism, Etlik City Hospital, Ankara, Turkey. ⁶Department of Medical Genetics, Ankara Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey. ⁷Department of Pediatric Endocrinology, Ankara Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey. ⁸Department of Paediatric Endocrinology, Hacettepe University Faculty of Medicine, Ankara, Turkey

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

Patients and Methods: Patients who underwent a THRβ gene analysis between September 2019 and September 2023 were retrospectively reviewed. We extracted the presenting characteristics, laboratory and hormonal features and molecular genetics analysis results from the patient’s hospital files.

Results: 47 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 THRβ gene in 30 patients from 8 unrelated families. Although most patients with RTHβ were asymptomatic, 6 patients had various symptoms. Seven patients had received various inappropriate treatments before diagnosis. Thyroid autoantibody was positive in 23% of all cases, 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 17 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 THRβ gene mutation database with 3 novel mutations. 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.