ESPE Abstracts

Introduction: Congenital hypothyroidism (CH) is one of the most common endocrine disorder in neonates. A minority arises from dyshormonogenesis, an inborn error of thyroid hormone synthesis. Blood tests commonly reveal elevated thyroid-stimulating hormone levels, decreased thyroxine and thyroglobulin may be low or even undetectable. Thyroid ultrasonography could present a normally sized or enlarged gland. Thyroid scans might demonstrate atypical uptake patterns. This study aims to investigate the features of dyshormonogenesis who has polygenic mutations.

Methods: A study of 120 patients with CH, a subset of individuals with dyshormonogenesis was identified for this study, focusing on those with multiple gene mutations. The study categorized the identified mutations based on their allelic presentation into monoallelic and biallelic groups. Along with NGS, clinical assessment included thyroid ultrasonography (USG), thyroid scan, thyroid function tests (TFT). The continuation of levothyroxine therapy was also monitored, providing a multidimensional perspective on the management of the disorder.

Results: In the study of monoallelic mutation group (n = 18), 10 patients had mutations in the DUOX2 gene, 6 in the TG gene, 1 in the TSHR gene, and 1 in the TRH gene. Among these patients, 12 discontinued levothyroxine while 6 continued the medication. Aside from continuity of medication, no other significant differences were observed between two groups. Contrastingly, in the biallelic mutation group (n = 4), all the patients discontinued levothyroxine. The analysis did not reveal a definitive association with TFT, thyroid USG, or scan outcomes between two groups.

Conclusion: Our findings indicate that the monoallelic or biallelic of gene mutations may be a determining factor in the maintenance of levothyroxine therapy among patients with CH due to dyshormonogenesis. The genetic distinction enriches an understanding of the genetic foundation influencing the course of treatment. However, the conclusions drawn from this study are limited by the small sample size of patients, which may not fully represent the dyshormonogenesis. Further research is necessary to determine how these genetic factors might influence therapeutic continuity in a broader population of patients with dyshormonogenesis.