Background: Telomerase reverse transcriptase (TERT) promoter mutations are associated with increased recurrence and mortality in patients with thyroid carcinoma. Previous studies on TERT promoter mutations were retrospectively conducted on a limited number of patients. Methods: We prospectively collected data on all consecutive patients who underwent thyroid carcinoma surgery between January 2019 and December 2020 at the Samsung Medical Center, Seoul, Korea. We included 2,092 patients with thyroid carcinoma. Results: Of 2,092 patients, 72 patients (3.4%) had TERT promoter mutations. However, the frequency of TERT promoter mutations was 0.5% in papillary thyroid microcarcinoma (PTMC) ≤1 cm and it was 5.8% in papillary thyroid carcinoma (PTC) >1 cm. The frequency of TERT promoter mutations was significantly associated with older age at diagnosis (odds ratio [OR], 1.12; P<0.001), larger primary tumor size (OR, 2.02; P<0.001), and aggressive histological type (OR, 7.78 in follicular thyroid carcinoma; OR, 10.33 in poorly differentiated thyroid carcinoma; OR, 45.92 in anaplastic thyroid carcinoma; P<0.001). Advanced T stage, advanced N stage, and distant metastasis at diagnosis were highly prevalent in mutated thyroid cancers. However, initial distant metastasis was not present in patients with TERT promoter mutations in PTMC. Although the C228T mutation was more highly detected than the C250T mutation (64 cases vs. 7 cases), there were no significant clinicopathological differences. Conclusion:This study is the first attempt to investigate the frequency of TERT promoter mutations in a real-world setting. The frequency of TERT promoter mutations in PTC was lower than expected, and in PTMC, young patients, and female patients, the frequency was very low.

Purpose Telomerase reverse transcriptase (TERT) promoter mutations are a poor prognostic factor in differentiated thyroid carcinoma (DTC). However, their prognostic value in anaplastic thyroid carcinoma (ATC) is unclear. Therefore, we investigated whether TERT promoter mutations also act as an independent poor prognostic factor in ATC. Methods We reviewed the medical records of 28 patients with ATC who underwent the TERT promoter mutations test at Samsung Medical Center between November 1995 and May 2020. The aggressive treatment group was defined as patients who underwent surgery, external radiotherapy, and systemic therapy. Results Among 28 patients, TERT promoter mutations were found in 10 patients (35.7%). There were no differences in the clinicopathological characteristics between the TERT-mutant and wild-type groups except tumor size and treatment modality. Median tumor size in the TERT-mutant group was 5.9 cm (3.7–11.0), which was significantly larger than that in the wild-type group (4.2 cm, 0.8–6.8, P = 0.006). Aggressive treatment was performed more frequently in the TERT-mutant group (60.0% vs. 22.2%, P = 0.046). The median overall survival (OS) was 6.9 months (0.4–39.5). The OS of the TERT-mutant group was longer that of than the wild-type group, but the difference was not significant (9.1 months [0.4–39.5] vs. 6.1 months [0.4–39.0], P = 0.432). In multiple regression analysis, old age (≥ 68.5 years), lymph node metastasis, and distant metastasis were significant prognostic factors, but TERT promoter mutations were not. Conclusion Unlike DTC, TERT promoter mutations were not an independent poor prognostic factor in ATC.

Background: Thyroxine-binding globulin (TBG) is a major transporter protein for thyroid hormones. The serpin family A member 7 (SERPINA7) gene codes for TBG, and mutations of the SERPINA7 gene result in TBG deficiency. Although more than 40 mutations have been reported in several countries, only a few studies of TBG deficiency and SERPINA7 gene mutation have been performed in Korea. The aim of this study is to review the clinical presentations and laboratory findings of patients with TBG deficiency and to investigate the types of SERPINA7 gene mutation. Methods: Five unrelated Korean adults with TBG deficiency attending endocrinology clinic underwent SERPINA7 gene sequencing. Four patients harbored a SERPINA7 gene mutation. Serum thyroid hormones, anti-microsomal antibodies, and TBG were measured. Genomic DNA was extracted from whole blood. All exons and intron-exon boundaries of the TBG gene were amplified and sequencing was performed. Results: Two patients were heterozygous females, and the other two were hemizygous males. One heterozygous female had coexisting hypothyroidism. The other heterozygous female was erroneously prescribed levothyroxine at a local clinic. One hemizygous male harbored a novel mutation, p.Phe269Cysfs*18, which caused TBG partial deficiency. Three patients had the p.Leu372Phefs*23 mutation, which is known as TBG-complete deficiency Japan (TBG-CDJ) and was also presented in previous mutation analyses in Korea. Conclusion:This study presents four patients diagnosed with TBG deficiency and provides the results of SERPINA7 gene sequencing. One novel mutation, p.Phe269Cysfs*18, causing TBD-partial deficiency and three cases of TBG-CDJ were demonstrated. It is necessary to identify TBG deficiency to prevent improper treatment. Also, sequencing of the SERPINA7 gene would provide valuable information about the TBG variants in Korea.