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Thyroid
Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach
Chan Kwon Jung, Andrey Bychkov, Kennichi Kakudo
Endocrinol Metab. 2022;37(5):703-718.   Published online October 4, 2022
DOI: https://doi.org/10.3803/EnM.2022.1553
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AbstractAbstract PDFPubReader   ePub   
The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes, and a grading system. Follicular cell-derived neoplasms are categorized into three families (classes): benign tumors, low-risk neoplasms, and malignant neoplasms. The terms “follicular nodular disease” and “differentiated high-grade thyroid carcinoma” are introduced to account for multifocal hyperplastic/neoplastic lesions and differentiated thyroid carcinomas with high-grade features, respectively. The term “Hürthle cells” is replaced with “oncocytic cells.” Invasive encapsulated follicular and cribriform morular variants of papillary thyroid carcinoma (PTC) are now redefined as distinct tumor types, given their different genetic alterations and clinicopathologic characteristics from other PTC subtypes. The term “variant” to describe a subclass of tumor has been replaced with the term “subtype.” Instead, the term “variant” is reserved to describe genetic alterations. A histologic grading system based on the mitotic count, necrosis, and/or the Ki67 index is used to identify high-grade follicular-cell derived carcinomas and medullary thyroid carcinomas. The 2022 WHO classification introduces the following new categories: “salivary gland-type carcinomas of the thyroid” and “thyroid tumors of uncertain histogenesis.” This review summarizes the major changes in the 2022 WHO classification and their clinical relevance.

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Thyroid
Thyroid Function across the Lifespan: Do Age-Related Changes Matter?
John P. Walsh
Endocrinol Metab. 2022;37(2):208-219.   Published online April 14, 2022
DOI: https://doi.org/10.3803/EnM.2022.1463
  • 9,036 View
  • 405 Download
  • 16 Web of Science
  • 19 Crossref
AbstractAbstract PDFPubReader   ePub   
Circulating concentrations of thyrotropin (TSH) and thyroxine (T4) are tightly regulated. Each individual has setpoints for TSH and free T4 which are genetically determined, and subject to environmental and epigenetic influence. Pituitary-thyroid axis setpoints are probably established in utero, with maturation of thyroid function continuing until late gestation. From neonatal life (characterized by a surge of TSH and T4 secretion) through childhood and adolescence (when free triiodothyronine levels are higher than in adults), thyroid function tests display complex, dynamic patterns which are sexually dimorphic. In later life, TSH increases with age in healthy older adults without an accompanying fall in free T4, indicating alteration in TSH setpoint. In view of this, and evidence that mild subclinical hypothyroidism in older people has no health impact, a strong case can be made for implementation of age-related TSH reference ranges in adults, as is routine in children.

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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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  • 12 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

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Thyroid
Big Data Articles (National Health Insurance Service Database)
Repeated Low High-Density Lipoprotein Cholesterol and the Risk of Thyroid Cancer: A Nationwide Population- Based Study in Korea
Jinyoung Kim, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Kyungdo Han, Hyuk-Sang Kwon
Endocrinol Metab. 2022;37(2):303-311.   Published online April 6, 2022
DOI: https://doi.org/10.3803/EnM.2021.1332
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  • 15 Web of Science
  • 15 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
High-density lipoprotein cholesterol (HDL-C) plays an important role in the reverse cholesterol transport pathway and prevents atherosclerosis-mediated disease. It has also been suggested that HDL-C may be a protective factor against cancer. However, an inverse correlation between HDL-C and cancer has not been established, and few studies have explored thyroid cancer.
Methods
The study participants received health checkups provided by the Korean National Health Insurance Service from 2009 to 2013 and were followed until 2019. Considering the variability of serum HDL-C level, low HDL-C level was analyzed by grouping based on four consecutive health checkups. The data analysis was performed using univariate and multivariate Cox proportional hazard regression models.
Results
A total of 3,134,278 total study participants, thyroid cancer occurred in 16,129. In the crude model, the hazard ratios for the association between repeatedly measured low HDL-C levels and thyroid cancer were 1.243, 1.404, 1.486, and 1.680 (P for trend <0.01), respectively, which were significant even after adjusting for age, sex, lifestyle factors, and metabolic diseases. The subgroup analysis revealed that low HDL-C levels likely had a greater impact on the group of patients with central obesity (P for interaction= 0.062), high blood pressure (P for interaction=0.057), impaired fasting glucose (P for interaction=0.051), and hyperlipidemia (P for interaction=0.126).
Conclusion
Repeatedly measured low HDL-C levels can be considered a risk factor for cancer as well as vascular disease. Low HDL-C levels were associated with the risk of thyroid cancer, and this correlation was stronger in a metabolically unhealthy population.

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Thyroid
Big Data Articles (National Health Insurance Service Database)
Recent Changes in the Incidence of Thyroid Cancer in Korea between 2005 and 2018: Analysis of Korean National Data
Yun Mi Choi, Jiwoo Lee, Mi Kyung Kwak, Min Ji Jeon, Tae Yong Kim, Eun-Gyoung Hong, Won Bae Kim, Won Gu Kim
Endocrinol Metab. 2022;37(5):791-799.   Published online October 11, 2022
DOI: https://doi.org/10.3803/EnM.2022.1533
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  • 13 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background
In this study, we evaluated the recent changes in the standardized, age-specific, stage-specific incidence rates (IRs) of thyroid cancer in Korea and compared them with the incidence data reported by the Surveillance, Epidemiology, and End Results Program.
Methods
The analysis was conducted using the incidence data (2005 to 2018) from the Statistics Korea and Korea Central Cancer Registry.
Results
The age-standardized IR (SIR) of thyroid cancer increased from 24.09 per 100,000 in 2005 to 74.83 in 2012 (annual percent change [APC], 14.5). From 2012 to 2015, the SIR decreased to 42.52 (APC, –17.9) and then remained stable until 2018 (APC, 2.1). This trend was similar in both men and women. Regarding age-specific IRs, the IRs for ages of 30 years and older showed a trend similar to that of the SIR; however, for ages below 30 years, no significant reduction was observed from the vertex of IR in 2015. Regarding stage-specific IRs, the increase was more prominent in those with regional disease (APC, 17.4) than in those with localized disease until 2012; then, the IR decreased until 2015 (APC, –16.1). The average APC from 2005 to 2018 increased in men, those under the age of 30 years, and those with regional disease.
Conclusion
The SIR in Korea peaked in 2012 and decreased until 2015 and then remained stable until 2018. However, in young individuals under the age of 30 years, the IR did not significantly decrease but tended to increase again. In terms of stage-specific IRs, the sharpest increase was seen among those with regional disease.

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    Yun Mi Choi, Min-Ju Kim, Jiwoo Lee, Mi Kyung Kwak, Min Ji Jeon, Tae Yong Kim, Eun-Gyoung Hong, Won Bae Kim, Won Gu Kim
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Thyroid
Diagnostic Performance of Thyroid Core Needle Biopsy Using the Revised Reporting System: Comparison with Fine Needle Aspiration Cytology
Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, So Lyung Jung, Chan Kwon Jung
Endocrinol Metab. 2022;37(1):159-169.   Published online February 28, 2022
DOI: https://doi.org/10.3803/EnM.2021.1299
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  • 10 Web of Science
  • 12 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We aim to validate the diagnostic performance of thyroid core needle biopsy (CNB) for diagnosing malignancy in clinical settings to align with the changes made in recently updated thyroid CNB guidelines.
Methods
We retrospectively analyzed 1,381 thyroid CNB and 2,223 fine needle aspiration (FNA) samples. The FNA and CNB slides were interpreted according to the Bethesda System for Reporting Thyroid Cytopathology and updated practice guidelines for thyroid CNB, respectively.
Results
Compared to FNA, CNB showed lower rates of inconclusive results: categories I (2.8% vs. 11.2%) and III (1.2% vs. 6.2%), and higher rates of categories II (60.9% vs. 50.4%) and IV (17.5% vs. 2.0%). The upper and lower bounds of the risk of malignancy (ROM) for category IV of CNB were 43.2% and 26.6%, respectively. The CNB subcategory IVb with nuclear atypia had a higher ROM than the subcategory without nuclear atypia (40%–62% vs. 23%–36%). In histologically confirmed cases, there was no significant difference in the diagnostic performance between CNB and FNA for malignancy. However, neoplastic diseases were more frequently detected by CNB than by FNA (88.8% vs. 77.6%, P=0.046). In category IV, there was no difference in unnecessary surgery rate between CNB and FNA (4.7% vs. 6.9%, P=0.6361).
Conclusion
Thyroid CNB decreased the rate of inconclusive results and showed a higher category IV diagnostic rate than FNA. The revised guidelines for thyroid CNB proved to be an excellent reporting system for assessing thyroid nodules.

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Close layer
Thyroid
Thyroid Cancer Screening
A Comprehensive Assessment of the Harms of Fine-Needle Aspiration Biopsy for Thyroid Nodules: A Systematic Review
Ji Yong Park, Wonsuk Choi, A Ram Hong, Jee Hee Yoon, Hee Kyung Kim, Ho-Cheol Kang
Endocrinol Metab. 2023;38(1):104-116.   Published online February 27, 2023
DOI: https://doi.org/10.3803/EnM.2023.1669
  • 6,846 View
  • 208 Download
  • 7 Web of Science
  • 11 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
There have concerns related with the potential harms of fine-needle aspiration biopsy (FNAB). We aimed to summarize the clinical complications and evaluate the safety of FNAB.
Methods
Studies related with the harms of FNAB were searched on MEDLINE, Embase, Cochrane library, and KoreaMed from 2012 to 2022. Also, studies reviewed in the previous systematic reviews were evaluated. Included clinical complications were postprocedural pain, bleeding events, neurological symptoms, tracheal puncture, infections, post-FNAB thyrotoxicosis, and needle tract implantation of thyroid cancers.
Results
Twenty-three cohort studies were included in this review. Nine studies which were related with FNAB-related pain showed that most of the subjects had no or mild discomfort. The 0% to 6.4% of the patients had hematoma or hemorrhage after FNAB, according to 15 studies. Vasovagal reaction, vocal cord palsy, and tracheal puncture have rarely described in the included studies. Needle tract implantation of thyroid malignancies was described in three studies reporting 0.02% to 0.19% of the incidence rate.
Conclusion
FNAB is considered to be a safe diagnostic procedure with rare complications, which are mainly minor events. Thorough assessement of the patients’ medical condition when deciding to perform FNABs would be advisable to lower potential complications.

Citations

Citations to this article as recorded by  
  • A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules
    Eun Kyung Lee, Young Joo Park, Chan Kwon Jung, Dong Gyu Na
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    Lairce Cristina Ribeiro Brito, Iara Beatriz De Carvalho Botêlho, Lanna Matos Silva Fernandes, Nayze Lucena Sangreman Aldeman, Uziel Nunes Silva
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Close layer
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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  • 190 Download
  • 6 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   ePub   
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-TIRADS1.5 (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-TIRADS1.5.
Conclusion
The unnecessary biopsy rate of the 2021 K-TIRADS1.5 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

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    Shaza Samargandy, Aliaa H. Ghoneim
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    Miguel Ángel Castilla Villanueva, Dania Guadalupe Solis Cano, Ana Amador Martínez, Marco Antonio Téliz Meneses, Jesús Baquera-Heredia, Cesar Eduardo Vallin Orozco, Mónica Loya Ceballos
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    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
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    International Journal for Innovation Education and Research.2023; 11(6): 8.     CrossRef
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Review Articles
Thyroid
Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Maternal Thyroid Dysfunction, and Child Autism Spectrum Disorder
Hyeong-Moo Shin, Jiwon Oh, Rebecca J. Schmidt, Elizabeth N. Pearce
Endocrinol Metab. 2022;37(6):819-829.   Published online November 23, 2022
DOI: https://doi.org/10.3803/EnM.2022.1598
  • 7,457 View
  • 147 Download
  • 6 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
Autism spectrum disorder (ASD), with its high economic and societal costs, is a growing public health concern whose prevalence has risen steadily over the last two decades. Although actual increased incidence versus improved diagnosis remains controversial, the increased prevalence of ASD suggests non-inherited factors as likely contributors. There is increasing epidemiologic evidence that abnormal maternal thyroid function during pregnancy is associated with increased risk of child ASD and other neurodevelopmental disorders. Prenatal exposure to endocrine-disrupting chemicals such as per- and polyfluoroalkyl substances (PFAS) is known to disrupt thyroid function and can affect early brain development; thus, thyroid dysfunction is hypothesized to mediate this relationship. The concept of a potential pathway from prenatal PFAS exposure through thyroid dysfunction to ASD etiology is not new; however, the extant literature on this topic is scant. The aim of this review is to evaluate and summarize reports with regard to potential mechanisms in this pathway.

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    Elizabeth N. Pearce
    Endocrine Practice.2024; 30(2): 172.     CrossRef
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    Zoe B. Kaplan, Elizabeth N. Pearce, Sun Y. Lee, Hyeong-Moo Shin, Rebecca J. Schmidt
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    G.V. Koulini, Vignesh Vinayagam, Indumathi M. Nambi, R. Ravi Krishna
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    Xiushuai Du, Yitian Wu, Gonghua Tao, Jun Xu, Zhiyuan Du, Minjuan Wu, Tianmin Gu, Jiasheng Xiong, Shuo Xiao, Xiao Wei, Yuanyuan Ruan, Ping Xiao, Ling Zhang, Weiwei Zheng
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    Bhagyashree Bharal, Chanda Ruchitha, Paarth Kumar, Rukmani Pandey, Mahesh Rachamalla, Som Niyogi, Ravi Naidu, Ravinder K. Kaundal
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    Jun Hyung Lee, Sung-Eun Cho
    Laboratory Medicine Online.2023; 13(3): 129.     CrossRef
Close layer
Thyroid
Preclinical Models of Follicular Cell-Derived Thyroid Cancer: An Overview from Cancer Cell Lines to Mouse Models
Min Ji Jeon, Bryan R. Haugen
Endocrinol Metab. 2022;37(6):830-838.   Published online December 26, 2022
DOI: https://doi.org/10.3803/EnM.2022.1636
  • 3,461 View
  • 209 Download
  • 7 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
The overall prognosis of thyroid cancer is excellent, but some patients have grossly invasive disease and distant metastases with limited responses to systemic therapies. Thus, relevant preclinical models are needed to investigate thyroid cancer biology and novel treatments. Different preclinical models have recently emerged with advances in thyroid cancer genetics, mouse modeling and new cell lines. Choosing the appropriate model according to the research question is crucial to studying thyroid cancer. This review will discuss the current preclinical models frequently used in thyroid cancer research, from cell lines to mouse models, and future perspectives on patient-derived and humanized preclinical models in this field.

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    Junying Qu, Yimeng Fang, Runchao Tao, Jing Zhao, Ting Xu, Rongbing Chen, Junbei Zhang, Kaikai Meng, Qinsi Yang, Kun Zhang, Xiaoqing Yan, Da Sun, Xia Chen
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    Hye Choi, Kwangsoon Kim
    International Journal of Molecular Sciences.2023; 24(13): 11138.     CrossRef
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    Zhen Xu, Hyo Shik Shin, Yoo Hyung Kim, Seong Yun Ha, Jae-Kyung Won, Su-jin Kim, Young Joo Park, Sareh Parangi, Sun Wook Cho, Kyu Eun Lee
    Frontiers in Immunology.2023;[Epub]     CrossRef
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    Fan Liang, Hongyan Xu, Hongwei Cheng, Yabo Zhao, Junhe Zhang
    Cancer Gene Therapy.2023; 30(11): 1443.     CrossRef
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    Luis Javier Leandro-García, Iñigo Landa
    Endocrinology.2023;[Epub]     CrossRef
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    Linyun Tan, Yitian Wang, Xin Hu, Guifeng Du, Xiaodi Tang, Li Min
    Biomolecules.2023; 13(9): 1362.     CrossRef
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Letter
Thyroid
Re-Increasing Trends in Thyroid Cancer Incidence after a Short Period of Decrease in Korea: Reigniting the Debate on Ultrasound Screening
Chan Kwon Jung, Ja Seong Bae, Young Joo Park
Endocrinol Metab. 2022;37(5):816-818.   Published online October 11, 2022
DOI: https://doi.org/10.3803/EnM.2022.1586
  • 2,790 View
  • 183 Download
  • 7 Web of Science
  • 8 Crossref
PDFPubReader   ePub   

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  • Bilateral axillo-breast approach robotic total thyroidectomy without isthmectomy: a case report
    Hyeji Kim, Hyeonuk Hwang, Hyungju Kwon
    The Ewha Medical Journal.2024;[Epub]     CrossRef
  • Contents analysis of thyroid cancer-related information uploaded to YouTube by physicians in Korea: endorsing thyroid cancer screening, potentially leading to overdiagnosis
    EunKyo Kang, HyoRim Ju, Soojeong Kim, Juyoung Choi
    BMC Public Health.2024;[Epub]     CrossRef
  • 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
  • Thyroid Cancer Incidence Among Korean Individuals: A Comparison of South Korea and the United States
    Dohun Kim, Guan Li, Peter K. Moon, Yifei Ma, Soohyun Sim, Sung Y. Park, Minkyung Oh, Uchechukwu C. Megwalu
    The Laryngoscope.2024; 134(9): 4156.     CrossRef
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    Kyeong Jin Kim, Jimi Choi, Sue K. Park, Young Joo Park, Sin Gon Kim
    International Journal of Surgery.2024; 110(9): 5489.     CrossRef
  • 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
    Endocrinology and Metabolism.2023; 38(1): 81.     CrossRef
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    Jinyoung Kim, Kyungdo Han, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon
    The Korean Journal of Internal Medicine.2023; 38(4): 526.     CrossRef
  • Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population
    Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Jaseong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chulmin Kim
    Journal of Korean Medical Science.2023;[Epub]     CrossRef
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Original Articles
Thyroid
BRAFV600E Mutation Enhances Estrogen-Induced Metastatic Potential of Thyroid Cancer by Regulating the Expression of Estrogen Receptors
Minjun Kim, Su-jin Kim, Seong Yun Ha, Zhen Xu, Youngjin Han, Hyeon-Gun Jee, Sun Wook Cho, Young Joo Park, Kyu Eun Lee
Endocrinol Metab. 2022;37(6):879-890.   Published online December 26, 2022
DOI: https://doi.org/10.3803/EnM.2022.1563
  • 3,905 View
  • 234 Download
  • 6 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAFV600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAFV600E on the estrogen-induced increase in metastatic potential in thyroid cancer.
Methods
Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAFV600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAFV600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data.
Results
Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAFV600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAFV600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis.
Conclusion
Our data show that BRAFV600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAFV600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

Citations

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  • The importance of protein domain mutations in cancer therapy
    Kiran Kumar Chitluri, Isaac Arnold Emerson
    Heliyon.2024; 10(6): e27655.     CrossRef
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    John D. Christensen, Hiba T. Basheer
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    John David Christensen, Hiba T Basheer, Jose Joaquin Lado Abeal
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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
  • 3,201 View
  • 140 Download
  • 6 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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  
  • 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
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    Giorgio Grani, Marialuisa Sponziello, Sebastiano Filetti, Cosimo Durante
    Nature Reviews Endocrinology.2024;[Epub]     CrossRef
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    Kyeong Jin Kim, Jimi Choi, Sue K. Park, Young Joo Park, Sin Gon Kim
    International Journal of Surgery.2024; 110(9): 5489.     CrossRef
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    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
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    Giorgio Grani
    Clinical Thyroidology.2023; 35(5): 192.     CrossRef
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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
  • 2,647 View
  • 182 Download
  • 7 Web of Science
  • 7 Crossref
AbstractAbstract PDFPubReader   ePub   
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
  • Thyroid cancer-specific mortality during 2005–2018 in Korea, aftermath of the overdiagnosis issue: a nationwide population-based cohort study
    Kyeong Jin Kim, Jimi Choi, Sue K. Park, Young Joo Park, Sin Gon Kim
    International Journal of Surgery.2024; 110(9): 5489.     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
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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
  • 4,499 View
  • 155 Download
  • 6 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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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    Jin Wang, Ke Wan, Xin Chang, Rui-Feng Mao
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    Han-Sang Baek, Jinyoung Kim, Chaiho Jeong, Jeongmin Lee, Jeonghoon Ha, Kwanhoon Jo, Min-Hee Kim, Tae Seo Sohn, Ihn Suk Lee, Jong Min Lee, Dong-Jun Lim
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    Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
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    Guillaume Goudot, Yanis Berkane, Eloi de Clermont-Tonnerre, Claire Guinier, Irina Filz von Reiterdank, Antonia van Kampen, Korkut Uygun, Curtis L. Cetrulo, Basak E. Uygun, Anahita Dua, Alexandre G. Lellouch
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