ESPE Abstracts

Introduction: The most common cause of elevated TSH is iodine deficiency, and other common causes are drug use, systemic diseases, and underlying genetic conditions.

Objective: We aimed to investigate molecular genetic etiology, genotype-phenotype relationships and the follow-up data in cases with elevated TSH initiated on L-thyroxine treatment

Methods: We retrospectively evaluated clinical features, laboratory values (TSH, free T4), demographics, age of drug onset and withdrawal, ultrasonography (USG), and genetic analysis results of the patients with elevated TSH. The study did not include those with a syndromic disease, concomitant disease, and drug use that may cause TSH elevation. The pathogenicity of the variants detected in the cases that underwent clinical exome sequencing with the targeted next-generation sequencing panel (Illumina TruSight One) was determined by the ACMG criteria.

Results: Twenty-eight of the 43 cases (65%) were male, 15 (35%) were female. The mean age at admission was 1.23±2.88 years. Age at presentation of 16 (37%) cases who were diagnosed with screening was 0.10±0.13 years, TSH 84.3±124 mU/L, fT4: 0.88±0.57 ng/dl at admission and 9 (56%) of these had dysgenesis. In total, 12 (28%) of 43 cases were diagnosed with dysgenesis, and 31 (72%) were diagnosed with dyshormonogenesis. The age of presentation who admitted with incidental TSH elevation outside the neonatal period was 1.64±3.33 years, and their TSH and T4 values were 80.2±137.3 mU/L and 0.96±0.40 ng/dl. L-Thyroxine treatment was terminated at 2.2±0.48 in 2 patients (12.5%) admitted from screening and at 2.79±1.60 in 4 (15%) in non-screening cases. Seven cases (43%) from screening were evaluated as transient hypothyroidism. In 5 (12%) of all cases, TG, 4 (10%) DUOX2, 3 (7%) TSHR gene heterozygous variants were detected. No disease-causing variant was found in 53 genes previously known to be associated with hypothyroidism, in 14 (87%) of 16 patients referred from the screening program and in 17 (63%) of 27 patients with coincidental TSH elevation, in a total of 31 (72%) cases.

Conclusion: There is limited knowledge regarding the genetic etiology of TSH elevation, which frequently occurs in pediatric endocrinology practice. Panel studies in such genetically diverse diseases are critical for increasing the mutation detection rate. More research is needed to determine the etiological causes in this population.