Endocrinology and Metabolism

Original Articles

Thyroid
The Diagnostic Role of Repeated Biopsy of Thyroid Nodules with Atypia of Undetermined Significance with Architectural Atypia on Core-Needle Biopsy: Hye Hyeon Moon, Sae Rom Chung, Young Jun Choi, Tae-Yon Sung, Dong Eun Song, Tae Yong Kim, Jeong Hyun Lee, Jung Hwan Baek; Endocrinol Metab. 2024;39(2):300-309. Published online January 3, 2024; DOI: https://doi.org/10.3803/EnM.2023.1818

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Abstract PDF Supplementary Material PubReader ePub: Background
We aimed to evaluate the utility of repeat biopsy of thyroid nodules classified as atypia of undetermined significance with architectural atypia (IIIB) on core-needle biopsy (CNB).
Methods
This retrospective study evaluated patients with thyroid nodules categorized as IIIB on CNB between 2013 and 2015. Demographic characteristics, subsequent biopsy results, and ultrasound (US) images were evaluated. The malignancy rates of nodules according to number of CNBs and the number of IIIB diagnoses was compared. Demographic and US features were evaluated to determine factors predictive of malignancy.
Results
Of 1,003 IIIB nodules on CNB, the final diagnosis was determined for 328 (32.7%) nodules, with 121 of them confirmed as malignant, resulting in a malignancy rate of 36.9% (95% confidence interval, 31.7% to 42.1%). Repeat CNB was performed in 248 nodules (24.7%), with 75 (30.2%), 131 (52.8%), 13 (5.2%), 26 (10.5%), one (0.4%), and two (0.8%) reclassified into categories II, IIIB, IIIA, IV, V, and VI, respectively. Malignancy rates were not significantly affected by the number of CNBs (P=0.291) or the number of IIIB diagnoses (P=0.473). None of the nodules confirmed as category II on repeat CNB was malignant. US features significantly associated with malignancy (P<0.003) included solid composition, irregular margins, microcalcifications, and high suspicion on the US risk stratification system.
Conclusion
Repeat biopsy of nodules diagnosed with IIIB on CNB did not increase the detection of malignancy but can potentially reduce unnecessary surgery. Repeat biopsy should be performed selectively, with US features guiding the choice between repeat biopsy and diagnostic surgery.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study: Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun; Endocrinol Metab. 2023;38(6):770-781. Published online November 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1726

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Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population.
Methods
Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model.
Results
During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m², and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death.
Conclusion
Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Thyroid Thyroid Cancer Screening
Diagnostic Performance of Ultrasound-Based Risk Stratification Systems for Thyroid Nodules: A Systematic Review and Meta-Analysis: Leehi Joo, Min Kyoung Lee, Ji Ye Lee, Eun Ju Ha, Dong Gyu Na; Endocrinol Metab. 2023;38(1):117-128. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1670

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Background
This study investigated the diagnostic performance of biopsy criteria in four society ultrasonography risk stratification systems (RSSs) for thyroid nodules, including the 2021 Korean (K)-Thyroid Imaging Reporting and Data System (TIRADS).
Methods
The Ovid-MEDLINE, Embase, Cochrane, and KoreaMed databases were searched and a manual search was conducted to identify original articles investigating the diagnostic performance of biopsy criteria for thyroid nodules (≥1 cm) in four widely used society RSSs.
Results
Eleven articles were included. The pooled sensitivity and specificity were 82% (95% confidence interval [CI], 74% to 87%) and 60% (95% CI, 52% to 67%) for the American College of Radiology (ACR)-TIRADS, 89% (95% CI, 85% to 93%) and 34% (95% CI, 26% to 42%) for the American Thyroid Association (ATA) system, 88% (95% CI, 81% to 92%) and 42% (95% CI, 22% to 67%) for the European (EU)-TIRADS, and 96% (95% CI, 94% to 97%) and 21% (95% CI, 17% to 25%) for the 2016 K-TIRADS. The sensitivity and specificity were 76% (95% CI, 74% to 79%) and 50% (95% CI, 49% to 52%) for the 2021 K-TIRADS_1.5 (1.5-cm size cut-off for intermediate-suspicion nodules). The pooled unnecessary biopsy rates of the ACR-TIRADS, ATA system, EU-TIRADS, and 2016 K-TIRADS were 41% (95% CI, 32% to 49%), 65% (95% CI, 56% to 74%), 68% (95% CI, 60% to 75%), and 79% (95% CI, 74% to 83%), respectively. The unnecessary biopsy rate was 50% (95% CI, 47% to 53%) for the 2021 K-TIRADS_1.5.
Conclusion
The unnecessary biopsy rate of the 2021 K-TIRADS_1.5 was substantially lower than that of the 2016 K-TIRADS and comparable to that of the ACR-TIRADS. The 2021 K-TIRADS may help reduce potential harm due to unnecessary biopsies.

Citations

Citations to this article as recorded by

To Screen or Not to Screen?
Do Joon Park
Endocrinology and Metabolism.2023; 38(1): 69. CrossRef
The 2017 United States Preventive Services Task Force Recommendation for Thyroid Cancer Screening Is No Longer the Gold Standard
Ka Hee Yi
Endocrinology and Metabolism.2023; 38(1): 72. CrossRef
Thyroid Cancer Screening: How to Maximize Its Benefits and Minimize Its Harms
Jung Hwan Baek
Endocrinology and Metabolism.2023; 38(1): 75. CrossRef
2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules
Young Joo Park, Eun Kyung Lee, Young Shin Song, Soo Hwan Kang, Bon Seok Koo, Sun Wook Kim, Dong Gyu Na, Seung-Kuk Baek, So Won Oh, Min Kyoung Lee, Sang-Woo Lee, Young Ah Lee, Yong Sang Lee, Ji Ye Lee, Dong-Jun Lim, Leehi Joo, Yuh-Seog Jung, Chan Kwon Jung
International Journal of Thyroidology.2023; 16(1): 1. CrossRef
Evaluation of the Appropriateness of Thyroid Fine-Needle Aspiration
Lairce Cristina Ribeiro Brito, Iara Beatriz De Carvalho Botêlho, Lanna Matos Silva Fernandes, Nayze Lucena Sangreman Aldeman, Uziel Nunes Silva
International Journal for Innovation Education and Research.2023; 11(6): 8. CrossRef

Thyroid Thyroid Cancer Screening
Survival Comparison of Incidentally Found versus Clinically Detected Thyroid Cancers: An Analysis of a Nationwide Cohort Study: Shinje Moon, Eun Kyung Lee, Hoonsung Choi, Sue K. Park, Young Joo Park; Endocrinol Metab. 2023;38(1):81-92. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1668

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Background
The true benefit of thyroid cancer screening is incompletely understood. This study investigated the impact of ultrasound screening on thyroid cancer outcomes through a comparison with symptomatic thyroid cancer using data from a nationwide cohort study in Korea.
Methods
Cox regression analysis was performed to assess the hazard ratios (HRs) for all-cause and thyroid cancer-specific mortality. Considering the possible bias arising from age, sex, year of thyroid cancer registration, and confounding factors for mortality (including smoking/drinking status, diabetes, and hypertension), all analyses were conducted with stabilized inverse probability of treatment weighting (IPTW) according to the route of detection.
Results
Of 5,796 patients with thyroid cancer, 4,145 were included and 1,651 were excluded due to insufficient data. In comparison with the screening group, the clinical suspicion group was associated with large tumors (17.2±14.6 mm vs. 10.4±7.9 mm), advanced T stage (3–4) (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09 to 1.41), extrathyroidal extension (OR, 1.16; 95% CI, 1.02 to 1.32), and advanced stage (III–IV) (OR, 1.16; 95% CI, 1.00 to 1.35). In IPTW-adjusted Cox regression analysis, the clinical suspicion group had significantly higher risks of all-cause mortality (HR, 1.43; 95% CI, 1.14 to 1.80) and thyroid cancer-specific mortality (HR, 3.07; 95% CI, 1.77 to 5.29). Mediation analysis showed that the presence of thyroid-specific symptoms was directly associated with a higher risk of cancer-specific mortality. Thyroid-specific symptoms also indirectly affected thyroid cancer-specific mortality, mediated by tumor size and advanced clinicopathologic status.
Conclusion
Our findings provide important evidence for the survival benefit of early detection of thyroid cancer compared to symptomatic thyroid cancer.

Citations

Citations to this article as recorded by

Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chul-Min Kim
Endocrinology and Metabolism.2024; 39(2): 310. CrossRef
Clinical Characteristics, Diagnostic Approach and Outcome of Thyroid Incidental Findings vs. Clinically Overt Thyroid Nodules: An Observational Single-Centre Study
Tom Jansen, Nike Stikkelbroeck, Annenienke van de Ven, Ilse van Engen-van Grunsven, Marcel Janssen, Han Bonenkamp, Martin Gotthardt, Romana T. Netea-Maier
Cancers.2023; 15(8): 2350. CrossRef
Lower Thyroid Cancer Mortality in Patients Detected by Screening: A Meta-Analysis
Shinje Moon, Young Shin Song, Kyong Yeun Jung, Eun Kyung Lee, Young Joo Park
Endocrinology and Metabolism.2023; 38(1): 93. CrossRef
To Screen or Not to Screen?
Do Joon Park
Endocrinology and Metabolism.2023; 38(1): 69. CrossRef
The 2017 United States Preventive Services Task Force Recommendation for Thyroid Cancer Screening Is No Longer the Gold Standard
Ka Hee Yi
Endocrinology and Metabolism.2023; 38(1): 72. CrossRef
Thyroid Cancer Screening: How to Maximize Its Benefits and Minimize Its Harms
Jung Hwan Baek
Endocrinology and Metabolism.2023; 38(1): 75. CrossRef

Thyroid Thyroid Cancer Screening
Lower Thyroid Cancer Mortality in Patients Detected by Screening: A Meta-Analysis: Shinje Moon, Young Shin Song, Kyong Yeun Jung, Eun Kyung Lee, Young Joo Park; Endocrinol Metab. 2023;38(1):93-103. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1667

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Background
Thyroid cancer screening has contributed to the skyrocketing prevalence of thyroid cancer. However, the true benefit of thyroid cancer screening is not fully understood. This study aimed to evaluate the impact of screening on the clinical outcomes of thyroid cancer by comparing incidental thyroid cancer (ITC) with non-incidental thyroid cancer (NITC) through a meta-analysis.
Methods
PubMed and Embase were searched from inception to September 2022. We estimated and compared the prevalence of high-risk features (aggressive histology of thyroid cancer, extrathyroidal extension, metastasis to regional lymph nodes or distant organs, and advanced tumor-node-metastasis [TNM] stage), thyroid cancer-specific death, and recurrence in the ITC and NITC groups. We also calculated pooled risks and 95% confidence intervals (CIs) of the outcomes derived from these two groups.
Results
From 1,078 studies screened, 14 were included. In comparison to NITC, the ITC group had a lower incidence of aggressive histology (odds ratio [OR], 0.46; 95% CI, 0.31 to 0.7), smaller tumors (mean difference, −7.9 mm; 95% CI, −10.2 to −5.6), lymph node metastasis (OR, 0.64; 95% CI, 0.48 to 0.86), and distant metastasis (OR, 0.42; 95% CI, 0.23 to 0.77). The risks of recurrence and thyroid cancer-specific mortality were also lower in the ITC group (OR, 0.42; 95% CI, 0.25 to 0.71 and OR, 0.46; 95% CI, 0.28 to 0.74) than in the NITC group.
Conclusion
Our findings provide important evidence of a survival benefit from the early detection of thyroid cancer compared to symptomatic thyroid cancer.

Citations

Citations to this article as recorded by

To Screen or Not to Screen?
Do Joon Park
Endocrinology and Metabolism.2023; 38(1): 69. CrossRef
The 2017 United States Preventive Services Task Force Recommendation for Thyroid Cancer Screening Is No Longer the Gold Standard
Ka Hee Yi
Endocrinology and Metabolism.2023; 38(1): 72. CrossRef
Thyroid Cancer Screening: How to Maximize Its Benefits and Minimize Its Harms
Jung Hwan Baek
Endocrinology and Metabolism.2023; 38(1): 75. CrossRef
Delayed Surgery for and Outcomes of Papillary Thyroid Cancer: Is the Pendulum Still Swinging?
Giorgio Grani
Clinical Thyroidology.2023; 35(5): 192. CrossRef

Review Article

Calcium & Bone Metabolism
Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism: Hye-Sun Park, Namki Hong, Jong Ju Jeong, Mijin Yun, Yumie Rhee; Endocrinol Metab. 2022;37(5):744-755. Published online October 25, 2022; DOI: https://doi.org/10.3803/EnM.2022.1589

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Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi–single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient’s clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.

Citations

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Expression of the Calcium-Sensing Receptor on Normal and Abnormal Parathyroid and Thyroid Tissue
Anne L. Worth, Mesrop Ayrapetyan, Susan J. Maygarden, Zibo Li, Zhanhong Wu, Chris B. Agala, Lawrence T. Kim
Journal of Surgical Research.2024; 293: 618. CrossRef
Use of [18F]fluorocholine PET/CT in the detection of primary hyperparathyroidism in paediatrics: a case report
Helena Martínez Sánchez, Francisca Moreno Macián, Sara León Cariñena, Carmen de Mingo Alemany, Lidia Blasco González, Raquel Sánchez Vañó
Journal of Pediatric Endocrinology and Metabolism.2024;[Epub] CrossRef
A Rare Case of Hyperfunctioning Lipoadenoma Presenting as a Cystic Pararthyroid Lesion
Jinyoung Kim, Ohjoon Kwon, Tae-Jung Kim, So Lyung Jung, Eun Ji Han, Ki-Ho Song
Journal of Bone Metabolism.2023; 30(2): 201. CrossRef
Role of 18F-Fluorocholine Positron Emission Tomography (PET)/Computed Tomography (CT) in Diagnosis of Elusive Parathyroid Adenoma
Janan R Badier, Pokhraj P Suthar, Jagadeesh S Singh, Miral D Jhaveri
Cureus.2023;[Epub] CrossRef
Pitfalls of DualTracer 99m-Technetium (Tc) Pertechnetate and Sestamibi Scintigraphy before Parathyroidectomy: Between Primary-Hyperparathyroidism-Associated Parathyroid Tumour and Ectopic Thyroid Tissue
Mara Carsote, Mihaela Stanciu, Florina Ligia Popa, Oana-Claudia Sima, Eugenia Petrova, Anca-Pati Cucu, Claudiu Nistor
Medicina.2023; 60(1): 15. CrossRef
Diagnostic Performance of Magnetic Resonance Imaging for Parathyroid Localization of Primary Hyperparathyroidism: A Systematic Review
Max H. M. C. Scheepers, Zaid Al-Difaie, Lloyd Brandts, Andrea Peeters, Bjorn Winkens, Mahdi Al-Taher, Sanne M. E. Engelen, Tim Lubbers, Bas Havekes, Nicole D. Bouvy, Alida A. Postma
Diagnostics.2023; 14(1): 25. CrossRef

Original Articles

Thyroid
Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients: Heera Yang, Hyunju Park, Hyun Jin Ryu, Jung Heo, Jung-Sun Kim, Young Lyun Oh, Jun-Ho Choe, Jung Han Kim, Jee Soo Kim, Hye Won Jang, Tae Hyuk Kim, Sun Wook Kim, Jae Hoon Chung; Endocrinol Metab. 2022;37(4):652-663. Published online July 22, 2022; DOI: https://doi.org/10.3803/EnM.2022.1477

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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.

Citations

Citations to this article as recorded by

TERT Promoter Mutations Frequency Across Race, Sex, and Cancer Type
Talal El Zarif, Marc Machaalani, Rashad Nawfal, Amin H Nassar, Wanling Xie, Toni K Choueiri, Mark Pomerantz
The Oncologist.2024; 29(1): 8. CrossRef
Gene mutations as predictors of central lymph mode metastasis in cN0 PTC: A meta‐analysis
Jiaqi Ji, Xinlong Shi
Clinical Genetics.2024; 105(2): 130. CrossRef
Risk stratification by combining common genetic mutations and TERT promoter methylation in papillary thyroid cancer
Ye Sang, Guanghui Hu, Junyu Xue, Mengke Chen, Shubin Hong, Rengyun Liu
Endocrine.2024;[Epub] CrossRef
Shortened telomere length in peripheral blood leukocytes is associated with cumulative radioactive iodine doses in patients with differentiated thyroid carcinoma
Hoonsung Choi, Sun Wook Cho, Hwan Hee Kim, Ka Hee Yi, Do Joon Park, Young Joo Park
Cancer.2024;[Epub] CrossRef
2023 Update of the Korean Thyroid Association Guidelines for the Management of Thyroid Nodules
Eun Kyung Lee, Young Joo Park
Clinical Thyroidology®.2024; 36(4): 153. CrossRef
Deciphering the Functions of Telomerase Reverse Transcriptase in Head and Neck Cancer
Tsung-Jang Yeh, Chi-Wen Luo, Jeng-Shiun Du, Chien-Tzu Huang, Min-Hung Wang, Tzer-Ming Chuang, Yuh-Ching Gau, Shih-Feng Cho, Yi-Chang Liu, Hui-Hua Hsiao, Li-Tzong Chen, Mei-Ren Pan, Hui-Ching Wang, Sin-Hua Moi
Biomedicines.2023; 11(3): 691. CrossRef
2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules
Young Joo Park, Eun Kyung Lee, Young Shin Song, Soo Hwan Kang, Bon Seok Koo, Sun Wook Kim, Dong Gyu Na, Seung-Kuk Baek, So Won Oh, Min Kyoung Lee, Sang-Woo Lee, Young Ah Lee, Yong Sang Lee, Ji Ye Lee, Dong-Jun Lim, Leehi Joo, Yuh-Seog Jung, Chan Kwon Jung
International Journal of Thyroidology.2023; 16(1): 1. CrossRef
Thyroid Cancer, Iodine, and Gene Mutation
Jae Hoon Chung
International Journal of Thyroidology.2023; 16(1): 89. CrossRef
Mortality rate and causes of death in papillary thyroid microcarcinoma
Jung Heo, Hyun Jin Ryu, Hyunju Park, Tae Hyuk Kim, Sun Wook Kim, Young Lyun Oh, Jae Hoon Chung
Endocrine.2023; 83(3): 671. CrossRef
TERT promoter mutations in thyroid cancer
Michiko Matsuse, Norisato Mitsutake
Endocrine Journal.2023; 70(11): 1035. CrossRef
TERT Promoter and BRAF V600E Mutations in Papillary Thyroid Cancer: A Single-Institution Experience in Korea
Min Jhi Kim, Jin Kyong Kim, Gi Jeong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Woong Youn Chung, Daham Kim, Kee-Hyun Nam
Cancers.2022; 14(19): 4928. CrossRef
Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients (Endocrinol Metab 2022;37:652-63, Heera Yang et al.)
Hyunju Park, Jae Hoon Chung
Endocrinology and Metabolism.2022; 37(6): 949. CrossRef
Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients (Endocrinol Metab 2022;37:652-63, Heera Yang et al.)
Sue Youn Kim, Chan Kwon Jung
Endocrinology and Metabolism.2022; 37(6): 947. CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Cumulative Exposure to High γ-Glutamyl Transferase Level and Risk of Diabetes: A Nationwide Population-Based Study: Ji-Yeon Park, Kyungdo Han, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim, Seung-Hwan Lee; Endocrinol Metab. 2022;37(2):272-280. Published online April 13, 2022; DOI: https://doi.org/10.3803/EnM.2022.1416

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Background
Elevated γ-glutamyl transferase (γ-GTP) level is associated with metabolic syndrome, impaired glucose tolerance, and insulin resistance, which are risk factors for type 2 diabetes. We aimed to investigate the association of cumulative exposure to high γ-GTP level with risk of diabetes.
Methods
Using nationally representative data from the Korean National Health Insurance system, 346,206 people who were free of diabetes and who underwent 5 consecutive health examinations from 2005 to 2009 were followed to the end of 2018. High γ-GTP level was defined as those in the highest quartile, and the number of exposures to high γ-GTP level ranged from 0 to 5. Hazard ratio (HR) and 95% confidence interval (CI) for diabetes were analyzed using the multivariable Cox proportional-hazards model.
Results
The mean follow-up duration was 9.2±1.0 years, during which 15,183 (4.4%) patients developed diabetes. There was a linear increase in the incidence rate and the risk of diabetes with cumulative exposure to high γ-GTP level. After adjusting for possible confounders, the HR of diabetes in subjects with five consecutive high γ-GTP levels were 2.60 (95% CI, 2.47 to 2.73) in men and 3.05 (95% CI, 2.73 to 3.41) in women compared with those who never had a high γ-GTP level. Similar results were observed in various subgroup and sensitivity analyses.
Conclusion
There was a linear relationship between cumulative exposure to high γ-GTP level and risk of diabetes. Monitoring and lowering γ-GTP level should be considered for prevention of diabetes in the general population.

Citations

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Validation of Estimated Small Dense Low-Density Lipoprotein Cholesterol Concentration in a Japanese General Population
Keisuke Endo, Ryo Kobayashi, Makito Tanaka, Marenao Tanaka, Yukinori Akiyama, Tatsuya Sato, Itaru Hosaka, Kei Nakata, Masayuki Koyama, Hirofumi Ohnishi, Satoshi Takahashi, Masato Furuhashi
Journal of Atherosclerosis and Thrombosis.2023;[Epub] CrossRef
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study
Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun
Endocrinology and Metabolism.2023; 38(6): 770. CrossRef
Elevated gamma‐glutamyl transferase to high‐density lipoprotein cholesterol ratio has a non‐linear association with incident diabetes mellitus: A second analysis of a cohort study
Haofei Hu, Yong Han, Mijie Guan, Ling Wei, Qijun Wan, Yanhua Hu
Journal of Diabetes Investigation.2022; 13(12): 2027. CrossRef
Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio: A valuable predictor of type 2 diabetes mellitus incidence
Wangcheng Xie, Bin Liu, Yansong Tang, Tingsong Yang, Zhenshun Song
Frontiers in Endocrinology.2022;[Epub] CrossRef

Thyroid
Usefulness of Real-Time Quantitative Microvascular Ultrasonography for Differentiation of Graves’ Disease from Destructive Thyroiditis in Thyrotoxic Patients: Han-Sang Baek, Ji-Yeon Park, Chai-Ho Jeong, Jeonghoon Ha, Moo Il Kang, Dong-Jun Lim; Endocrinol Metab. 2022;37(2):323-332. Published online April 13, 2022; DOI: https://doi.org/10.3803/EnM.2022.1413

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Background
Microvascular ultrasonography (MVUS) is a third-generation Doppler technique that was developed to increase sensitivity compared to conventional Doppler. The purpose of this study was to compare MVUS with conventional color Doppler (CD) and power Doppler (PD) imaging to distinguish Graves’ disease (GD) from destructive thyroiditis (DT).
Methods
This prospective study included 101 subjects (46 GDs, 47 DTs, and eight normal controls) from October 2020 to November 2021. All ultrasonography examinations were performed using microvascular flow technology (MV-Flow). The CD, PD, and MVUS images were semi-quantitatively graded according to blood flow patterns. On the MVUS images, vascularity indices (VIs), which were the ratio (%) of color pixels in the total grayscale pixels in a defined region of interest, were obtained automatically. Receiver operating characteristic curve analysis was performed to verify the diagnostic performance of MVUS. The interclass correlation coefficient and Cohen’s kappa analysis were used to analyze the reliability of MVUS (ClinicalTrials.gov:NCT04879173).
Results
The area under the curve (AUC) for CD, PD, MVUS, and MVUS-VI was 0.822, 0.844, 0.808, and 0.852 respectively. The optimal cutoff value of the MVUS-VI was 24.95% for distinguishing GD and DT with 87% sensitivity and 80.9% specificity. We found a significant positive correlation of MVUS-VI with thyrotropin receptor antibody (r=0.554) and with thyroid stimulating immunoglobulin bioassay (r=0.841). MVUS showed high intra- and inter-observer reliability from various statistical method.
Conclusion
In a real time and quantitative manner, MVUS-VI could be helpful to differentiate GD from thyroiditis in thyrotoxic patients, with less inter-observer variability.

Citations

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Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management
Jin Wang, Ke Wan, Xin Chang, Rui-Feng Mao
World Journal of Diabetes.2024; 15(3): 348. CrossRef
The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
Endocrinology and Metabolism.2023; 38(3): 338. CrossRef
Duplex Hemodynamic Parameters of Both Superior and Inferior Thyroid Arteries in Evaluation of Thyroid Hyperfunction Disorders
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Thyroid
Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea: Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Yea Eun Kang, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim; Endocrinol Metab. 2021;36(5):1078-1085. Published online October 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1151

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Background
Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis.
Methods
This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009.
Results
The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS).
Conclusion
The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.

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Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma
Lindsay A. Bischoff, Ian Ganly, Laura Fugazzola, Erin Buczek, William C. Faquin, Bryan R. Haugen, Bryan McIver, Caitlin P. McMullen, Kate Newbold, Daniel J. Rocke, Marika D. Russell, Mabel Ryder, Peter M. Sadow, Eric Sherman, Maisie Shindo, David C. Shonk
JAMA Otolaryngology–Head & Neck Surgery.2024; 150(3): 265. CrossRef
Oncocytic carcinoma of the thyroid: Conclusions from a 20‐year patient cohort
Nelson R. Gruszczynski, Shahzeb S. Hasan, Ana G. Brennan, Julian De La Chapa, Adithya S. Reddy, David N. Martin, Prem P. Batchala, Edward B. Stelow, Eric M. Dowling, Katherine L. Fedder, Jonathan C. Garneau, David C. Shonka
Head & Neck.2024;[Epub] CrossRef
Hurthle cell carcinoma: a rare variant of thyroid malignancy – a case report
Yuvraj Adhikari, Anupama Marasini, Nawaraj Adhikari, Laxman D. Paneru, Binit Upadhaya Regmi, Manita Raut
Annals of Medicine & Surgery.2023; 85(5): 1940. CrossRef
Hürthle Cell Carcinoma: Single Center Analysis and Considerations for Surgical Management Based on the Recent Literature
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Thyroid
Comparison of Korean vs. American Thyroid Imaging Reporting and Data System in Malignancy Risk Assessment of Indeterminate Thyroid Nodules: Sunyoung Kang, Seul Ki Kwon, Hoon Sung Choi, Min Joo Kim, Young Joo Park, Do Joon Park, Sun Wook Cho; Endocrinol Metab. 2021;36(5):1111-1120. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1208

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Background
The management of cytologically indeterminate thyroid nodules is challenging for clinicians. This study aimed to compare the diagnostic performance of the Korean Thyroid Imaging Reporting and Data Systems (K-TIRADS) with that of the American College of Radiology (ACR)-TIRADS for predicting the malignancy risk of indeterminate thyroid nodules.
Methods
Thyroid nodules diagnosed by fine-needle aspiration (FNA) followed by surgery or core needle biopsy at a single referral hospital were enrolled.
Results
Among 200 thyroid nodules, 78 (39.0%) nodules were classified as indeterminate by FNA (Bethesda category III, IV, and V), and 114 (57.0%) nodules were finally diagnosed as malignancy by surgery or core needle biopsy. The area under the curve (AUC) was higher for FNA than for either TIRADS system in all nodules, while all three methods showed similar AUCs for indeterminate nodules. However, for Bethesda category III nodules, applying K-TIRADS 5 significantly increased the risk of malignancy compared to a cytological examination alone (50.0% vs. 26.5%, P=0.028), whereas applying ACR-TIRADS did not lead to a change.
Conclusion
K-TIRADS and ACR-TIRADS showed similar diagnostic performance in assessing indeterminate thyroid nodules, and K-TIRADS had beneficial effects for malignancy prediction in Bethesda category III nodules.

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Is the nodule location a predictive risk factor for cancer in AUS/FLUS thyroid nodules? A retrospective cohort study
Saad M. Alqahtani, Bassam A. Altalhi, Yousef S. Alalawi, Saif S. Al-Sobhi
Asian Journal of Surgery.2024;[Epub] CrossRef
Diagnostic Performance of Various Ultrasound Risk Stratification Systems for Benign and Malignant Thyroid Nodules: A Meta-Analysis
Ji-Sun Kim, Byung Guk Kim, Gulnaz Stybayeva, Se Hwan Hwang
Cancers.2023; 15(2): 424. CrossRef
The impact of thyroid imaging reporting and data system on the management of Bethesda III thyroid nodules
Saad M. Alqahtani, Saif S. Al-Sobhi, Mohammed A. Alturiqy, Riyadh I. Alsalloum, Hindi N. Al-Hindi
Journal of Taibah University Medical Sciences.2023; 18(3): 506. CrossRef
Diagnostic Performance of Six Ultrasound Risk Stratification Systems for Thyroid Nodules: A Systematic Review and Network Meta-Analysis
Do Hyun Kim, Sung Won Kim, Mohammed Abdullah Basurrah, Jueun Lee, Se Hwan Hwang
American Journal of Roentgenology.2023; 220(6): 791. CrossRef
Diagnostic efficiency among Eu-/C-/ACR-TIRADS and S-Detect for thyroid nodules: a systematic review and network meta-analysis
Longtao Yang, Cong Li, Zhe Chen, Shaqi He, Zhiyuan Wang, Jun Liu
Frontiers in Endocrinology.2023;[Epub] CrossRef
Comparison of diagnostic performance of two ultrasound risk stratification systems for thyroid nodules: a systematic review and meta-analysis
Yun Jin Kang, Hee Sun Ahn, Gulnaz Stybayeva, Ju Eun Lee, Se Hwan Hwang
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Yun Jin Kang, Gulnaz Stybayeya, Ju Eun Lee, Se Hwan Hwang
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Clinical Study
Molecular Correlates and Nuclear Features of Encapsulated Follicular-Patterned Thyroid Neoplasms: Chan Kwon Jung, Andrey Bychkov, Dong Eun Song, Jang-Hee Kim, Yun Zhu, Zhiyan Liu, Somboon Keelawat, Chiung-Ru Lai, Mitsuyoshi Hirokawa, Kaori Kameyama, Kennichi Kakudo; Endocrinol Metab. 2021;36(1):123-133. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.860

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Background
Assessing nuclear features is diagnostically challenging in the aspect of thyroid pathology. The aim of this study was to determine whether pathologists could distinguish BRAF-like and RAS-like nuclear features morphologically and identify morphological features to differentiate thyroid tumors with RAS-like mutations from encapsulated papillary thyroid carcinoma (PTC) with predominant follicular growth and BRAFV^600E mutation.
Methods
Representative whole slide images of 16 encapsulated thyroid tumors with predominant follicular growth were reviewed by 12 thyroid pathologists using a web browser-based image viewer. Total nuclear score was calculated from semi-quantitatively scored eight nuclear features. The molecular profile of RAS and BRAF genes was determined by Sanger sequencing.
Results
Total nuclear score ranging 0 to 24 could differentiate BRAF-like tumors from RAS-like tumors with a cut-off value of score 14. The interobserver agreement was the highest for the assessment of nuclear pseudoinclusions (NPIs) but the lowest for nuclear elongation and sickle-shaped nuclei. NPIs were found in tumors with BRAFV^600E mutation, but not in tumors with RAS-like mutations. Total nuclear scores were significantly higher for tumors with BRAFV^600E than for those with RAS-like mutations (P<0.001).
Conclusion
Our results suggest that NPIs and high nuclear scores have diagnostic utility as rule-in markers for differentiating PTC with BRAFV^600E mutation from benign or borderline follicular tumors with RAS-like mutations. Relaxation of rigid criteria for nuclear features resulted in an overdiagnosis of PTC. Immunostaining or molecular testing for BRAFV^600E mutation is a useful adjunct for cases with high nuclear scores to identify true PTC.

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Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study
Chankyung Kim, Shipra Agarwal, Andrey Bychkov, Jen-Fan Hang, Agnes Stephanie Harahap, Mitsuyoshi Hirokawa, Kennichi Kakudo, Somboon Keelawat, Chih-Yi Liu, Zhiyan Liu, Truong Phan-Xuan Nguyen, Chanchal Rana, Huy Gia Vuong, Yun Zhu, Chan Kwon Jung
Virchows Archiv.2024;[Epub] CrossRef
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Kun-Ping Shih, Yu-Cheng Lee, Jia-Jiun Tsai, Shu-Hui Lin, Chih-Yi Liu, Wan-Shan Li, Chien-Feng Li, Jen-Fan Hang
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The Presence of Typical “BRAFV600E-Like” Atypia in Papillary Thyroid Carcinoma is Highly Specific for the Presence of the BRAFV600E Mutation
John Turchini, Loretta Sioson, Adele Clarkson, Amy Sheen, Leigh Delbridge, Anthony Glover, Mark Sywak, Stan Sidhu, Anthony J. Gill
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David N Poller
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Agnes Stephanie Harahap, Imam Subekti, Sonar Soni Panigoro, Asmarinah, Lisnawati, Retno Asti Werdhani, Hasrayati Agustina, Dina Khoirunnisa, Mutiah Mutmainnah, Fajar Lamhot Gultom, Abdillah Hasbi Assadyk, Maria Francisca Ham
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The Asian Thyroid Working Group, from 2017 to 2023
Kennichi Kakudo, Chan Kwon Jung, Zhiyan Liu, Mitsuyoshi Hirokawa, Andrey Bychkov, Huy Gia Vuong, Somboon Keelawat, Radhika Srinivasan, Jen-Fan Hang, Chiung-Ru Lai
Journal of Pathology and Translational Medicine.2023; 57(6): 289. CrossRef
Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Tumour Entity with a Short History. A Review on Challenges in Our Microscopes, Molecular and Ultrasonographic Profile
Ivana Kholová, Elina Haaga, Jaroslav Ludvik, David Kalfert, Marie Ludvikova
Diagnostics.2022; 12(2): 250. CrossRef
Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach
Chan Kwon Jung, Andrey Bychkov, Kennichi Kakudo
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Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice
Kennichi Kakudo
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The Incidence of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Meta-Analysis Assessing Worldwide Impact of the Reclassification
Chanchal Rana, Huy Gia Vuong, Thu Quynh Nguyen, Hoang Cong Nguyen, Chan Kwon Jung, Kennichi Kakudo, Andrey Bychkov
Thyroid.2021;[Epub] CrossRef

Review Article

Thyroid
Mechanisms of TERT Reactivation and Its Interaction with BRAF^V600E: Young Shin Song, Young Joo Park; Endocrinol Metab. 2020;35(3):515-525. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.304

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The telomerase reverse transcriptase (TERT) gene, which is repressed in most differentiated human cells, can be reactivated by somatic TERT alterations and epigenetic modulations. Moreover, the recruitment, accessibility, and binding of transcription factors also affect the regulation of TERT expression. Reactivated TERT contributes to the development and progression of cancer through telomere lengthening-dependent and independent ways. In particular, because of recent advances in high-throughput sequencing technologies, studies on genomic alterations in various cancers that cause increased TERT transcriptional activity have been actively conducted. TERT reactivation has been reported to be associated with poor prognosis in several cancers, and TERT promoter mutations are among the most potent prognostic markers in thyroid cancer. In particular, when a TERT promoter mutation coexists with the BRAF^V600E mutation, these mutations exert synergistic effects on a poor prognosis. Efforts have been made to uncover the mechanisms of these synergistic interactions. In this review, we discuss the role of TERT reactivation in tumorigenesis, the mechanisms of TERT reactivation across all human cancers and in thyroid cancer, and the mechanisms of interactions between BRAF^V600E and TERT promoter mutations.

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Original Articles

Clinical Study
Effectiveness of Injecting Cold 5% Dextrose into Patients with Nerve Damage Symptoms during Thyroid Radiofrequency Ablation: Min Kyoung Lee, Jung Hwan Baek, Sae Rom Chung, Young Jun Choi, Yu-Mi Lee, Tae Yong Kim, Jeong Hyun Lee; Endocrinol Metab. 2020;35(2):407-415. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.407

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Background
Although radiofrequency ablation (RFA) is a safe treatment for thyroid tumors, nerve damage is a frequent complication. A previous retrospective study suggested that an injection of cold 5% dextrose in water (5% DW) can reduce nerve damage during RFA. This study validated the efficacy of injecting cold 5% DW for management of nerve damage during RFA.
Methods
Between November 2017 and December 2018, 242 patients underwent 291 RFA sessions for treatment of benign thyroid nodules or recurrent thyroid cancers. Using a standardized technique, cold (0°C to 4°C) 5% DW was immediately injected around the damaged nerve into patients with any symptoms suggesting nerve damage. The incidence of nerve damage, the volume of 5% DW injected, symptom recovery time and the incidence of permanent nerve damage were evaluated.
Results
Nineteen patients experienced nerve damage symptoms related to 21 RFA sessions, including 17 patients during 19 sessions and two patients on the day after two sessions. Patients with nerve damage symptoms detected during RFA were treated by injection of a mean 41 mL (range, 3 to 260) cold 5% DW, but the two patients who experienced symptoms the next day did not receive cold 5% DW injections. Immediate recovery was observed after 15 RFA sessions in 14 patients. No patient experienced permanent nerve damage.
Conclusion
Injection of cold 5% DW is effective in managing nerve damage during RFA of thyroid lesions.

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Pia Pace-Asciak, Jon O. Russell, Ralph P. Tufano
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Jia-Rui Du, Wen-Hui Li, Cheng-Hai Quan, Hui Wang, Deng-Ke Teng
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Continuous neuromonitoring during radiofrequency ablation of benign thyroid nodules provides objective evidence of laryngeal nerve safety
Catherine F. Sinclair, Maria J. Téllez, Roberto Peláez-Cruz, Alba Díaz-Baamonde, Sedat Ulkatan
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Clinical Study
Revisiting Rupture of Benign Thyroid Nodules after Radiofrequency Ablation: Various Types and Imaging Features: Sae Rom Chung, Jung Hwan Baek, Jin Yong Sung, Ji Hwa Ryu, So Lyung Jung; Endocrinol Metab. 2019;34(4):415-421. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.415

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Background

To evaluate the imaging features, clinical manifestations, and prognosis of patients with thyroid nodule rupture after radiofrequency ablation (RFA).

Methods

The records of 12 patients who experienced thyroid nodule rupture after RFA at four Korean thyroid centers between March 2010 and July 2017 were retrospectively reviewed. Clinical data evaluated included baseline patient characteristics, treatment methods, initial presenting symptoms, imaging features, treatment, and prognosis.

Results

The most common symptoms of post-RFA nodule rupture were sudden neck bulging and pain. Based on imaging features, the localization of nodule rupture was classified into three types: anterior, posterolateral, and medial types. The anterior type is the most often, followed by posterolateral and medial type. Eight patients recovered completely after conservative treatment. Four patients who did not improve with conservative management required invasive procedures, including incision and drainage or aspiration.

Conclusion

Thyroid nodule rupture after RFA can be classified into three types based on its localization: anterior, posterolateral, and medial types. Because majority of thyroid nodule ruptures after RFA can be managed conservatively, familiarity with these imaging features is essential in avoiding unnecessary imaging workup or invasive procedures.

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