ESPE Abstracts

Introduction: Thyroid hormone is known as greatly influence on growth and development in fetuses and newborns. If the detection of the disease is delayed, hypothyroidism can cause irreversible damage, so early detection and treatment is very important. Hypothyroidism can be divided into permanent and temporary cases depending on the duration of treatment, but there is no predictor that can completely differentiate those two. However, as genes related to hypothyroidism are revealed, genetic analysis can predict whether hypothyroidism will be permanent.

Method: Among the patients diagnosed with congenital hypothyroidism from July 2017 to December 2020 and being treated at Soonchunhyang University Seoul hospital, patients who want to implement the hypothyroidism NGS panel were enroll the study. A total of 147 patients were tested, and 30 genes (DUOX2, DUOXA2, FOXE1, GNAS1, HESX1, IYD, LHX3, NKX2-1, NKX2-5, PAX8, POU1F1, PROP1, SLC16A2, SLC5A5, SLC5A4, TG, THRA, THRB, TPO, TRH, TRHR, TSHB, TSHR, LHX4, SOX2, GLIS3, OTX2, DUOX1, IGSF1, SOX3) with more related genes were analyzed through hypothyroidism NGS panel.

Results: A total of 22 known pathogenic variants were identified in 20 patients; DUOXA2 9 times (40.9%), DUOX2 8 times (36.4%), and TSHR 5 times (22.7%). A total of 42 variants identified as likely pathogenic in 38 patients; DUOX2 28 times (66.7%), TSHR 7 times (16.7%), DUOXA2 2 times (4.8%), TG 2 times (4.8%), and each TPO, LHX3, PAX8 1 time (2.4%) in order of frequency. In addition, 121 VOUS variants were identified in 90 patients; DOUX2 40 times (33.1%), TG 27 times (22.3%), TPO 7 times (5.8%), GLIS3 6 times (5.0%), DUOX1, IGSF1 5 times (4.1%), GNAS1, LHX3, TSHR 4 times (3.3%), TBL1X, PAX8 3 times (2.5%), DUOXA2, LHX4, OTX2, SLC26A4 twice (1.7%), HESX1, NKX2-1, TRH, IYD, THRA once (1.1%). Among 147 patients, 50 patients (34%) had pathogenic or likely pathogenic genes and 33 patients (22.4%) had none of related mutations. There were 9 ectopic thyroid, 4 agenesis, 1 hemiplasia patient and 33 patients could stop treatment until now.

Conclusion: It is expected that causative genetic analysis of congenital hypothyroidism will be helpful in actively stopping the treatment of congenital hypothyroidism according to the clinical condition of the patient, except when the disease is estimated due to pathogenic or likely pathogenic genes.