ESPE Abstracts

Background: Congenital hypothyroidism is the most common neonatal metabolic disorder and detected at a rate of 1 in 3000 to 4000 live births. Compared to congenital hypothyroidism caused by defects in thyroid development leading to thyroid dysgenesis, thyroid dyshormonogenesis has tendency to be detected at older age and its clinical manifestations are individually different. Thus, to evaluate exact causes and predict clinical course for congenital thyroid dyshormonogenesis and establish precise strategies for treatment, we conduct Next-Generation Sequencing (NGS) to patients who diagnosed congenital hypothyroidism with normal thyroid gland and analysis the results.

Methods: We conducted NGS to 33 patients who visited Department of pediatrics, Inha university hospital and diagnosed congenital hypothyroidism with normal contour of thyroid gland in ultrasonography from Jan. 2018 to Mar. 2021. We also analyzed their thyroid function test results, dose of levothyroxine and clinical manifestations.

Results: From NGS analysis, 33 CH patients revealed that 26 patients (24/31, 77.42%) were detected to have at least one potentially functional variant. 6 DUOX2 variants in 7 patients, 6 DUOXA2 variants in 5 patient, 5 TG variants in 3 patients, 5 TSHR variants in 7 patients, 2 TPO variants in 2 patients, 1 NKX2-1 variant in 1 patient, 1 THRB variant in 1 patient, 1 TRH variant in 1 patient, 1 SLC5A5 variant in 1 patient and 2 GLIS-3 variants in 2 patients as PV, LPV and VUS types were confirmed. Siblings and parents of the patients who agreed and were available underwent familial sequencing analysis. In most of cases, parents who had one heterozygote variant of the gene were symptomatic or had subclinical hypothyroidism.

Conclusions: In this study, we found DUOX2/DUOXA2, TSHR and TG variants were dominant in patients who diagnosed CH in a single center. And we cautiously recommend that using the NGS to strategize treatment plan for CH based on the clinical manifestations and genetic analysis of the family members of the index patients. To this, further additional studies are needed.