ECEESPE2025 Poster Presentations Thyroid (141 abstracts)
Molecular characterization of a multicenter cohort of patients with non-autoimmune subclinical hypothyroidism
Núria González-Llorens 1 , María Antolín Mate 1 , Judith Gonzalez Morla 2 , Jordi Bosch Muñoz 3 , Sandra Ortigosa Gómez 4 , María Hernandedez Herrero 5 , Rosangela Tomasini 6 , Marta Murillo Valles 7 , Paula Casano Sancho 8 , Albert Feliu Rovira 9 , Elsa Puerto Carranza 10 , Ariadna Campos Martorell 11 , Eduard Mogas Viñals 11 , Cristina Aguilar Riera 11 , María Clemente León 11 & Diego Yeste Fernández 11
1Vall d’Hebron University Hospital, Barcelona, Spain; 2Hospital de Palamós, Palamós, Spain; 3Hospital Universitaria Arnau de Vilanova, Lleida, Spain; 4Hospital del Mar, Barcelona, Spain; 55Hospital Universitari Joan XXIII, Tarragona, Spain; 6Hospital Mútua de Terrassa, Terrassa, Spain; 7Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 8Hospital Sant Joan de Deu, Esplugues de Llobregat, Spain; 9Hospital Universitari Sant Joan de Reus, Reus, Spain; 10Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain; 11University Hospital Vall d’Hebron, Barcelona, Spain
JOINT2339
Introduction: Non-autoimmune subclinical hypothyroidism (NASHT) is characterized by elevated TSH levels with normal concentrations of thyroid hormones. Genetic defects, which can determine disorders in the biosynthesis process of thyroid hormones, such as in the TSH receptor (TSHR) or in the dual oxidase 2 (DUOX2) genes, have been described. It is suspected that other genes that regulate or participate in the biosynthesis of thyroid hormones could be involved in NASHT, suggesting a more complex pathogenesis although few studies have explored its genetic basis.
Objective: To perform a molecular characterization and genotype-phenotype correlation in NASHT patients.
Patients and methods: Multicenter study in 11 Spanish centers. Patients with NASHT were included with TSH>7 μUI/mL in two measurements. Patients exposed to medical treatments or radiotherapy capable of affecting thyroid function were excluded. The data collection were: clinical, familial, analytical, thyroid ultrasound, and levothyroxine treatment. Molecular analysis was performed using a high-throughput sequencing panel (Cell3 Target Custom Panel tier 2, NONACUS) covering 18 genes, the most relevant: TG, TPO, DUOX2, DUOXA2, PAX8, TSHR, SLC5A5, and SLC26A4. Statistical analysis: IBM®SPSS®Statistics v25.
Results: Ninety patients were studied (mean age at diagnosis 5.6±3.4 years; 58% male). Fifty patients (56%) received levothyroxine treatment. Mean TSH at diagnosis: 9.7±3.7 μUI/mL; maximum TSH: 11.7±4.4 μUI/mL. Thyroid ultrasound showed thyroid hypoplasia in 13 patients and hyperplasia in 2. A total of 55 patients (61%) had candidate variants in the studied genes, of which 44 (80%) were heterozygous, 9 (16%) digenic, and two were compound heterozygous; one for DUOX2 and another for TPO. In total, 64 candidate variants were identified, with their distribution in Table1. Among heterozygous patients, 21 (48%) had a variant described as pathogenic (PAT) or likely pathogenic (LPAT), and 23 (52%) had variants of uncertain significance (VUS). Family segregation studies are ongoing to determine the possible inheritance of candidate variants and their potential cosegregation with NASHT clinical features.
Conclusion: A significant proportion (61%) of NASHT patients have variants in thyroid dyshormonogenesis-related genes, some previously undescribed. The possible oligogenic origin of NASHT is highlighted, as 9 patients showed variants in two genes. These genetic findings may help to better characterize patients and define their prognosis and need for treatment. Additionally, given the high percentage of VUS identified, our results support the need for functional studies to determine the clinical relevance of these findings.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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