Endocrinology and Metabolism

Hyemi Kwon (Kwon H)

28 Articles

Diabetes, obesity and metabolism
Docosahexanoic Acid Attenuates Palmitate-Induced Apoptosis by Autophagy Upregulation via GPR120/mTOR Axis in Insulin-Secreting Cells: Seok-Woo Hong, Jinmi Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2024;39(2):353-363. Published online January 23, 2024; DOI: https://doi.org/10.3803/EnM.2023.1809

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Abstract PDF Supplementary Material PubReader ePub: Background
Polyunsaturated fatty acids (PUFAs) reportedly have protective effects on pancreatic β-cells; however, the underlying mechanisms are unknown.
Methods
To investigate the cellular mechanism of PUFA-induced cell protection, mouse insulinoma 6 (MIN6) cells were cultured with palmitic acid (PA) and/or docosahexaenoic acid (DHA), and alterations in cellular signaling and apoptosis were examined.
Results
DHA treatment remarkably repressed caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)-positive red dot signals in PA-treated MIN6 cells, with upregulation of autophagy, an increase in microtubule- associated protein 1-light chain 3 (LC3)-II, autophagy-related 5 (Atg5), and decreased p62. Upstream factors involved in autophagy regulation (Beclin-1, unc51 like autophagy activating kinase 1 [ULK1], phosphorylated mammalian target of rapamycin [mTOR], and protein kinase B) were also altered by DHA treatment. DHA specifically induced phosphorylation on S2448 in mTOR; however, phosphorylation on S2481 decreased. The role of G protein-coupled receptor 120 (GPR120) in the effect of DHA was demonstrated using a GPR120 agonist and antagonist. Additional treatment with AH7614, a GPR120 antagonist, significantly attenuated DHA-induced autophagy and protection. Taken together, DHA-induced autophagy activation with protection against PA-induced apoptosis mediated by the GPR120/mTOR axis.
Conclusion
These findings indicate that DHA has therapeutic effects on PA-induced pancreatic β-cells, and that the cellular mechanism of β-cell protection by DHA may be a new research target with potential pharmacotherapeutic implications in β-cell protection.

Diabetes, obesity and metabolism
Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway: Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Yu-Mi Lim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2024;39(1):98-108. Published online January 3, 2024; DOI: https://doi.org/10.3803/EnM.2023.1786

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Abstract PDF Supplementary Material PubReader ePub: Background
Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states.
Methods
Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco’s modified Eagle’s medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours.
Results
SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation.
Conclusion
These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

Diabetes, obesity and metabolism
Coronary Artery Calcium Score as a Sensitive Indicator of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A Long-Term Cohort Study: Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Sang Min Lee, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki Won Oh, Sung Rae Cho, Young-Hoon Jeong, Eun-Jung Rhee; Endocrinol Metab. 2023;38(5):568-577. Published online October 10, 2023; DOI: https://doi.org/10.3803/EnM.2023.1770

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Abstract PDF Supplementary Material PubReader ePub: Background
Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden.
Methods
We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease.
Results
The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100.
Conclusion
CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

Thyroid
The Current Status of Hyperthyroidism in Korea: Hyemi Kwon; Endocrinol Metab. 2023;38(4):392-394. Published online August 25, 2023; DOI: https://doi.org/10.3803/EnM.2023.401

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Miscellaneous
Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society: Hyemi Kwon, Eun Roh, Chang Ho Ahn, Hee Kyung Kim, Cheol Ryong Ku, Kyong Yeun Jung, Ju Hee Lee, Eun Heui Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Jun Sung Moon, Jin Hwa Kim, Mi-kyung Kim, The Committee of Clinical Practice Guideline of the Korean Endocrine Society; Endocrinol Metab. 2022;37(6):839-850. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1627

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Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

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Pembrolizumab plus lenvatinib for radically unresectable or metastatic renal cell carcinoma in the Japanese population
Ryo Fujiwara, Takeshi yuasa, kenichi kobayashi, tetsuya yoshida, susumu kageyama
Expert Review of Anticancer Therapy.2023; 23(5): 461. CrossRef
Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review
Won Sang Yoo, Eu Jeong Ku, Eun Kyung Lee, Hwa Young Ahn
Endocrinology and Metabolism.2023; 38(6): 750. CrossRef

Diabetes, Obesity and Metabolism
Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway: Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2022;37(1):74-83. Published online February 9, 2022; DOI: https://doi.org/10.3803/EnM.2021.1293

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Background
Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has been shown to reduce body weight and liver fat content in patients with type 2 diabetes. Family with sequence similarity 3 member A (FAM3A) plays a vital role in regulating glucose and lipid metabolism. The aim of this study was to determine the mechanisms by which dulaglutide protects against hepatic steatosis in HepG2 cells treated with palmitic acid (PA).
Methods
HepG2 cells were pretreated with 400 μM PA for 24 hours, followed by treatment with or without 100 nM dulaglutide for 24 hours. Hepatic lipid accumulation was determined using Oil red O staining and triglyceride (TG) assay, and the expression of lipid metabolism-associated factor was analyzed using quantitative real time polymerase chain reaction and Western blotting.
Results
Dulaglutide significantly decreased hepatic lipid accumulation and reduced the expression of genes associated with lipid droplet binding proteins, de novo lipogenesis, and TG synthesis in PA-treated HepG2 cells. Dulaglutide also increased the expression of proteins associated with lipolysis and fatty acid oxidation and FAM3A in PA-treated cells. However, exendin-(9-39), a GLP-1R antagonist, reversed the expression of FAM3A, and fatty acid oxidation-associated factors increased due to dulaglutide. In addition, inhibition of FAM3A by siRNA attenuated the reducing effect of dulaglutide on TG content and its increasing effect on regulation of fatty acid oxidation.
Conclusion
These results suggest that dulaglutide could be used therapeutically for improving nonalcoholic fatty liver disease, and its effect could be mediated in part via upregulation of FAM3A expression through a GLP-1R-dependent pathway.

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GLP-1/GLP-1RAs: New Options for the Drug Treatment of NAFLD
Haoran Jiang, Linquan Zang
Current Pharmaceutical Design.2024; 30(2): 100. CrossRef
GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives
Riccardo Nevola, Raffaella Epifani, Simona Imbriani, Giovanni Tortorella, Concetta Aprea, Raffaele Galiero, Luca Rinaldi, Raffaele Marfella, Ferdinando Carlo Sasso
International Journal of Molecular Sciences.2023; 24(2): 1703. CrossRef
FAM3A mediates the phenotypic switch of human aortic smooth muscle cells stimulated with oxidised low-density lipoprotein by influencing the PI3K-AKT pathway
Lei Yang, Baoshun Du, Shitao Zhang, Maode Wang
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ATP Secretion and Metabolism in Regulating Pancreatic Beta Cell Functions and Hepatic Glycolipid Metabolism
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Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
The Effects of Glucose Lowering Agents on the Secondary Prevention of Coronary Artery Disease in Patients with Type 2 Diabetes: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2021;36(5):977-987. Published online October 14, 2021; DOI: https://doi.org/10.3803/EnM.2021.1046

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Background
Patients with diabetes have a higher risk of requiring repeated percutaneous coronary intervention (PCI) than non-diabetic patients. We aimed to evaluate and compare the effects of anti-diabetic drugs on the secondary prevention of myocardial infarction among type 2 diabetes mellitus patients.
Methods
We analyzed the general health check-up dataset and claims data of the Korean National Health Insurance Service of 199,714 participants (age ≥30 years) who underwent PCIs between 2010 and 2013. Those who underwent additional PCI within 1 year of their first PCI (n=3,325) and those who died within 1 year (n=1,312) were excluded. Patients were classified according to their prescription records for glucose-lowering agents. The primary endpoint was the incidence rate of coronary revascularization.
Results
A total of 35,348 patients were included in the study. Metformin significantly decreased the risk of requiring repeat PCI in all patients (adjusted hazard ratio [aHR], 0.77). In obese patients with body mass index (BMI) ≥25 kg/m², patients treated with thiazolidinedione (TZD) exhibited a decreased risk of requiring repeat revascularization than those who were not treated with TZD (aHR, 0.77; 95% confidence interval, 0.63 to 0.95). Patients treated with metformin showed a decreased risk of requiring revascularization regardless of their BMI. Insulin, meglitinide, and alpha-glucosidase inhibitor were associated with increased risk of repeated PCI.
Conclusion
The risk of requiring repeat revascularization was lower in diabetic patients treated with metformin and in obese patients treated with TZD. These results suggest that physicians should choose appropriate glucose-lowering agents for the secondary prevention of coronary artery disease.

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Application of systemic inflammation indices and lipid metabolism-related factors in coronary artery disease
Zhuoyan Zhao, Huan Lian, Yixiang Liu, Lixian Sun, Ying Zhang
Coronary Artery Disease.2023; 34(5): 306. CrossRef
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Zhicheng Xu, Haidong Zhang, Chenghui Wu, Yuxiang Zheng, Jingzhou Jiang
Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef
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Huan Lian, Zhuoyan Zhao, Kelin Ma, Zhenjiang Ding, Lixian Sun, Ying Zhang
Clinical and Applied Thrombosis/Hemostasis.2022; 28: 107602962211392. CrossRef

Diabetes, Obesity and Metabolism
Changes in Insulin Resistance Index and the Risk of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease without Diabetes: Kangbuk Samsung Health Study: Dae-Jeong Koo, Mi Yeon Lee, Inha Jung, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2021;36(5):1016-1028. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1110

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Background
Fibrosis is the most important prognostic factor for nonalcoholic fatty liver disease (NAFLD). Insulin resistance plays a key role of fibrosis progression. We evaluated the association between changes in homeostasis model assessment of insulin resistance (HOMA-IR) values and changes in fibrosis status in NAFLD.
Methods
We analyzed the data of 15,728 participants with NAFLD (86% men, mean age 40.5 years) who had no diabetes at baseline and visited our centers for health check-ups both in 2012 and 2016. The participants were classified into four groups according to the degree of change in HOMA-IR values from baseline to the end of follow-up: G1 (<0), G2 (0–0.50), G3 (0.51–1.00), and G4 (>1.00). NAFLD was assessed by ultrasonography, and fibrosis status was evaluated by the NAFLD fibrosis score (NFS) and the aspartate aminotransferase to platelet ratio index (APRI).
Results
After the 4-year follow-up, the multivariable-adjusted odds ratio (OR) for progression of fibrosis probability increased with increasing HOMA-IR values (OR, 2.25; 95% confidence interval [CI], 1.87 to 2.71 for NFS; and OR, 2.55; 95% CI, 2.05 to 3.18 for APRI, G4). This tendency remained consistent throughout the subgroup analyses, except in those for female sex and a body mass index <25 kg/m². The OR for regression of fibrosis probability decreased with increasing HOMA-IR values (OR, 0.33; 95% CI, 0.25 to 0.43 for NFS, G4).
Conclusion
Changes in HOMA-IR values were associated with changes in fibrosis status in patients with NAFLD without diabetes, which underscores the role of insulin resistance in liver fibrosis.

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Yu Luo, Cuiyu Wang, Tian Zhang, Xiaoyu He, Jianan Hao, Andong Shen, Hang Zhao, Shuchun Chen, Luping Ren
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Impact of COVID-19 Lockdown on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Adults: A before and after Pandemic Lockdown Longitudinal Study
Ángel Arturo López-González, Bárbara Altisench Jané, Luis Masmiquel Comas, Sebastiana Arroyo Bote, Hilda María González San Miguel, José Ignacio Ramírez Manent
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Metabolic Score for Insulin Resistance Is Inversely Related to Incident Advanced Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease
Jun-Hyuk Lee, Yu-Jin Kwon, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn
Nutrients.2022; 14(15): 3039. CrossRef
Machine learning models including insulin resistance indexes for predicting liver stiffness in United States population: Data from NHANES
Kexing Han, Kexuan Tan, Jiapei Shen, Yuting Gu, Zilong Wang, Jiayu He, Luyang Kang, Weijie Sun, Long Gao, Yufeng Gao
Frontiers in Public Health.2022;[Epub] CrossRef
The crosstalk between insulin resistance and nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease: a culprit or a consequence?
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Miscellaneous
COVID-19 Vaccination for Endocrine Patients: A Position Statement from the Korean Endocrine Society: Cheol Ryong Ku, Kyong Yeun Jung, Chang Ho Ahn, Jun Sung Moon, Ju Hee Lee, Eun Heui Kim, Hyemi Kwon, Hee Kyung Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Eun Roh, Jin Hwa Kim, Mi-kyung Kim, the Committee of Clinical Practice Guideline of the Korean Endocrine Society; Endocrinol Metab. 2021;36(4):757-765. Published online August 17, 2021; DOI: https://doi.org/10.3803/EnM.2021.404

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Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.

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COVID-19 mRNA vaccine may trigger subacute thyroiditis
Mehmet Sözen, Ömercan Topaloğlu, Berrin Çetinarslan, Alev Selek, Zeynep Cantürk, Emre Gezer, Damla Köksalan, Taner Bayraktaroğlu
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Diabetes, Obesity and Metabolism
Increased Risk of Nonalcoholic Fatty Liver Disease in Individuals with High Weight Variability: Inha Jung, Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2021;36(4):845-854. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1098

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Background
Weight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes.
Methods
We examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years.
Results
On dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53).
Conclusion
Regardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

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Changes in Macronutrients during Dieting Lead to Weight Cycling and Metabolic Complications in Mouse Model
Anouk Charlot, Anthony Bringolf, Léa Debrut, Joris Mallard, Anne-Laure Charles, Emilie Crouchet, Delphine Duteil, Bernard Geny, Joffrey Zoll
Nutrients.2024; 16(5): 646. CrossRef
Body weight variability and the risk of liver‐related outcomes in type 2 diabetes and steatotic liver disease: a cohort study
Nathalie C. Leite, Claudia R. L. Cardoso, Cristiane A. Villela‐Nogueira, Gil F. Salles
Obesity.2024;[Epub] CrossRef
Weight variability, physical functioning and incident disability in older adults
Katie J. McMenamin, Tamara B. Harris, Joshua F. Baker
Journal of Cachexia, Sarcopenia and Muscle.2023; 14(4): 1648. CrossRef
Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway
Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Endocrinology and Metabolism.2022; 37(1): 74. CrossRef
Triglyceride and glucose index is a simple and easy‐to‐calculate marker associated with nonalcoholic fatty liver disease
Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
Obesity.2022; 30(6): 1279. CrossRef
Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight
Mohammed Eslam, Hashem B. El-Serag, Sven Francque, Shiv K. Sarin, Lai Wei, Elisabetta Bugianesi, Jacob George
Nature Reviews Gastroenterology & Hepatology.2022; 19(10): 638. CrossRef
Impact of COVID-19 Lockdown on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Adults: A before and after Pandemic Lockdown Longitudinal Study
Ángel Arturo López-González, Bárbara Altisench Jané, Luis Masmiquel Comas, Sebastiana Arroyo Bote, Hilda María González San Miguel, José Ignacio Ramírez Manent
Nutrients.2022; 14(14): 2795. CrossRef
Higher Weight Variability Could Bring You a Fatty Liver
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Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease
Inha Jung, Da Young Lee, Mi Yeon Lee, Hyemi Kwon, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Won-Young Lee, Sung-Woo Park, Se Eun Park
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Endocrine Research
Clusterin Protects Lipotoxicity-Induced Apoptosis via Upregulation of Autophagy in Insulin-Secreting Cells: Seok-Woo Hong, Jinmi Lee, Min Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2020;35(4):943-953. Published online December 2, 2020; DOI: https://doi.org/10.3803/EnM.2020.768

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Background
There is a great need to discover factors that could protect pancreatic β-cells from apoptosis and thus prevent diabetes mellitus. Clusterin (CLU), a chaperone protein, plays an important role in cell protection in numerous cells and is involved in various cellular mechanisms, including autophagy. In the present study, we investigated the protective role of CLU through autophagy regulation in pancreatic β-cells.
Methods
To identify the protective role of CLU, mouse insulinoma 6 (MIN6) cells were incubated with CLU and/or free fatty acid (FFA) palmitate, and cellular apoptosis and autophagy were examined.
Results
Treatment with CLU remarkably upregulated microtubule-associated protein 1-light chain 3 (LC3)-II conversion in a doseand time-dependent manner with a significant increase in the autophagy-related 3 (Atg3) gene expression level, which is a mediator of LC3-II conversion. Moreover, co-immunoprecipitation and fluorescence microscopy experiments showed that the molecular interaction of LC3 with Atg3 and p62 was markedly increased by CLU. Stimulation of LC3-II conversion by CLU persisted in lipotoxic conditions, and FFA-induced apoptosis and dysfunction were simultaneously improved by CLU treatment. Finally, inhibition of LC3-II conversion by Atg3 gene knockdown markedly attenuated the cytoprotective effect of CLU.
Conclusion
Taken together, these findings suggest that CLU protects pancreatic β-cells against lipotoxicity-induced apoptosis via autophagy stimulation mediated by facilitating LC3-II conversion. Thus, CLU has therapeutic effects on FFA-induced pancreatic β-cell dysfunction.

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Docosahexanoic Acid Attenuates Palmitate-Induced Apoptosis by Autophagy Upregulation via GPR120/mTOR Axis in Insulin-Secreting Cells
Seok-Woo Hong, Jinmi Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Endocrinology and Metabolism.2024; 39(2): 353. CrossRef
Exercise as a non-pharmacological intervention to protect pancreatic beta cells in individuals with type 1 and type 2 diabetes
Alexandra Coomans de Brachène, Corentin Scoubeau, Anyïshai E. Musuaya, Jose Maria Costa-Junior, Angela Castela, Julie Carpentier, Vitalie Faoro, Malgorzata Klass, Miriam Cnop, Decio L. Eizirik
Diabetologia.2023; 66(3): 450. CrossRef
Apolipoprotein J Attenuates Vascular Restenosis by Promoting Autophagy and Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells
Ning Yang, Bo Dong, Yanqiu Song, Yang Li, Lu Kou, Qin Qin
Journal of Cardiovascular Translational Research.2022; 15(5): 1086. CrossRef
Targets for rescue from fatty acid-induced lipotoxicity in pancreatic beta cells
Seok-Woo Hong, Won-Young Lee
Cardiovascular Prevention and Pharmacotherapy.2022; 4(2): 57. CrossRef
Co-regulators of autophagy and the cell cycle in HFD − As treated mice
Marzieh Zeinvand-Lorestani, Mohammad Javad Khodayar, Ali Teimoori, Najmaldin Saki, Akram Ahangarpour, Ali Ranjbar, Hamed Zeinvand-Lorestani
Journal of Trace Elements and Minerals.2022; 2: 100018. CrossRef
Targeting pancreatic β cells for diabetes treatment
Chirag Jain, Ansarullah, Sara Bilekova, Heiko Lickert
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Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies
Safia Costes, Gyslaine Bertrand, Magalie A. Ravier
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Clinical Study
The Prevalence and Risk of Type 2 Diabetes in Adults with Disabilities in Korea: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2020;35(3):552-561. Published online July 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.653

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Background
People with disabilities are at risk of secondary conditions such as diabetes. The aim of this study was to evaluate the prevalence and risk of type 2 diabetes in South Korea, especially among people with all types of disabilities.
Methods
We conducted a cross-sectional study using data from the Korean National Health Insurance Service, with two disabilityfree controls matched for each participant with disabilities by age and sex. Information regarding the type, severity and grade of disabilities was obtained based on the National Disability Registry. Diagnosis of type 2 diabetes was defined according to the following criteria: presence of International Classification of Diseases, Tenth Revision, Clinical Modification codes E11, E12, E13, or E14 and claims for at least one oral anti-diabetic agent or insulin at baseline, or fasting glucose level ≥126 mg/dL.
Results
We included 1,297,806 participants with disabilities and 2,943,719 control. Out of 4,241,525 participants, 841,990 (19.9%) were diagnosed with diabetes. The prevalence of diabetes was higher in the disability group compared with individuals without disabilities (23.1% vs. 18.4%). The odds of having diabetes was higher in the disability group compared with the control group (adjusted odds ratio, 1.34; 95% confidence interval, 1.33 to 1.34). The results showed higher prevalence of diabetes in the mildly disabled group (23.2%) than in the severely disabled group (22.7%).
Conclusion
The prevalence and risk of diabetes were higher in people with disabilities compared with the general population. Physicians and public health authorities should focus on people with disabilities for proper diabetes management.

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Bipolar disorder and the risk of cardiometabolic diseases, heart failure, and all-cause mortality: a population-based matched cohort study in South Korea
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Psychotic Disorders and the Risk of Type 2 Diabetes Mellitus, Atherosclerotic Cardiovascular Diseases, and All-Cause Mortality: A Population-Based Matched Cohort Study
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Hye Jin Nam, Ju Young Yoon, Wen-Jun Tu
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Jinwook Bahk, Hee-Yeon Kang, Young-Ho Khang
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Seon Mee Park, Hyun Jung Kim, Tae Uk Kang, Heather Swan, Hyeong Sik Ahn
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Cumulative exposure to impaired fasting glucose and future risk of type 2 diabetes mellitus
Mee Kyoung Kim, Kyungdo Han, Eun Sil Koh, Oak-Kee Hong, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon
Diabetes Research and Clinical Practice.2021; 175: 108799. CrossRef
Diabetes in People with Disabilities: a Call for Action
Inha Jung, Eun-Jung Rhee, Won-Young Lee
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Clinical Study
Serum Adiponectin and Progranulin Level in Patients with Benign Thyroid Nodule or Papillary Thyroid Cancer: Hyemi Kwon, Se Eun Park, Ji-Sup Yun, Cheol-Young Park; Endocrinol Metab. 2020;35(2):396-406. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.396

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Background
Obesity is associated with thyroid cancer risk. Adiponectin has insulin-sensitizing and anti-inflammatory effects, while progranulin is associated with inflammation and tumorigenesis. We investigated serum adiponectin and progranulin levels in patients with benign thyroid nodule (benign group) and papillary thyroid cancer (PTC; PTC group). The associations between these levels and the clinicopathological features of PTC were evaluated.
Methods
We included 157 patients who underwent thyroid surgery (17% of benign and 83% of PTC group). Clinicopathological features including size, lymph node metastasis, extrathyroidal extension (ETE), multifocality, American Thyroid Association risk stratification were evaluated.
Results
The age was 42.0 years, and 69% were female. Serum adiponectin and progranulin levels were 6.3 μg/mL and 101.5 ng/mL in the benign group and 5.4 μg/mL and 106.1 ng/mL in the PTC group, respectively (P=0.6 and P=0.4, respectively). Serum adiponectin levels showed no significant differences according to clinicopathological features of PTC. The proportions of patients with primary tumor size >1 cm were 3%, 5%, 8%, and 8% according to serum progranulin level quartiles, respectively (P=0.03). The proportions of patients with microscopic/gross ETE were 8%/0%, 9%/1%, 11%/1%, and 11%/2% according to serum progranulin level quartiles, respectively. Median serum progranulin level was significantly higher in patients with PTC >1 cm than in patients with papillary thyroid microcarcinoma (P=0.04, 115.3 ng/mL and 104.7 ng/mL, respectively).
Conclusion
Serum adiponectin and progranulin levels showed no significant difference between benign and PTC groups. Increased serum progranulin levels were significantly associated with PTC >1 cm and microscopic and gross ETE.

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Exploring the logic and conducting a comprehensive evaluation of AdipoRon-based adiponectin replacement therapy against hormone-related cancers—a systematic review
Lucas Fornari Laurindo, Andreline Franchi Sosin, Caroline Barbalho Lamas, Ricardo de Alvares Goulart, Jesselina Francisco dos Santos Haber, Claudia Rucco Penteado Detregiachi, Sandra Maria Barbalho
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Adiponectin Inhibits the Progression of Obesity-Associated Papillary Thyroid Carcinoma Through Autophagy
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Elisa Ventura, Giacomo Ducci, Reyes Benot Dominguez, Valentina Ruggiero, Antonino Belfiore, Elena Sacco, Marco Vanoni, Renato V. Iozzo, Antonio Giordano, Andrea Morrione
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Obesity and thyroid cancer risk
Lauren C. Burrage, Donald S.A. McLeod, Susan J. Jordan
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Progranulin promoted the proliferation, metastasis, and suppressed apoptosis via JAK2-STAT3/4 signaling pathway in papillary thyroid carcinoma
Yanxu Dong, Hao Tan, Lidong Wang, Zhen Liu
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Obesity and Thyroid Cancer Risk: An Update
Fabiana Franchini, Giuseppe Palatucci, Annamaria Colao, Paola Ungaro, Paolo Emidio Macchia, Immacolata Cristina Nettore
International Journal of Environmental Research and Public Health.2022; 19(3): 1116. CrossRef
Obesity and Overweight Are Associated with Minimal Extrathyroidal Extension, Multifocality and Bilaterality of Papillary Thyroid Cancer
Krzysztof Kaliszewski, Dorota Diakowska, Marta Rzeszutko, Jerzy Rudnicki
Journal of Clinical Medicine.2021; 10(5): 970. CrossRef
Adiponectin and Thyroid Cancer: Insight into the Association between Adiponectin and Obesity
Yuanyuan Zhou, Ying Yang, Taicheng Zhou, Bai Li, Zhanjian Wang
Aging and disease.2021; 12(2): 597. CrossRef

Clinical Study
Visceral-to-Subcutaneous Abdominal Fat Ratio Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis: Chan-Hee Jung, Eun-Jung Rhee, Hyemi Kwon, Yoosoo Chang, Seungho Ryu, Won-Young Lee; Endocrinol Metab. 2020;35(1):165-176. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.165

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Background

We evaluated the association of visceral-to-subcutaneous fat ratio (VSR) with nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis degree based on noninvasive serum fibrosis markers in the general population with NAFLD.

Methods

This is a cross-sectional study, in 7,465 Korean adults who underwent health screening examinations. NAFLD was defined as fatty liver detected on ultrasonography, and visceral and subcutaneous abdominal fat was measured using computed tomography. We predicted fibrosis based on the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI) and categorized the risk for advanced fibrosis as low, indeterminate, or high.

Results

The multivariable-adjusted prevalence ratios for indeterminate to high risk of advanced fibrosis based on FIB-4, determined by comparing the second, third, and fourth quartiles with the first quartile of VSR, were 3.38 (95% confidence interval [CI], 0.64 to 17.97), 9.41 (95% CI, 1.97 to 45.01), and 19.34 (95% CI, 4.06 to 92.18), respectively. The multivariable-adjusted prevalence ratios for intermediate to high degree of fibrosis according to APRI also increased across VSR quartiles (5.04 [95% CI, 2.65 to 9.59], 7.51 [95% CI, 3.91 to 14.42], and 19.55 [95% CI, 9.97 to 38.34], respectively). High VSR was more strongly associated with the prevalence of NAFLD in nonobese subjects than in obese subjects, and the associations between VSR and intermediate to high probability of advanced fibrosis in NAFLD were stronger in obese subjects than in nonobese subjects.

Conclusion

High VSR values predicted increased NAFLD risk and advanced fibrosis risk with NAFLD, and the predictive value of VSR for indeterminate to high risk of advanced fibrosis was higher in obese subjects than in nonobese subjects.

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Omar M. Mahmoud, Gehad Abd Elaziz Mahmoud, Haisam Atta, Wael A. Abbas, Hanan M. Ahmed, Mohamed A. A. Abozaid
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Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
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Thyroid
Letter: Thyroid-Stimulating Hormone Reference Ranges in the First Trimester of Pregnancy in an Iodine-Sufficient Country (Endocrinol Metab 2018;33:466-72, Carmen Castillo et al.): Hyemi Kwon; Endocrinol Metab. 2019;34(1):93-94. Published online March 21, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.93

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Endocrine Research
Deficiency of Sphingosine-1-Phosphate Reduces the Expression of Prohibitin and Causes β-Cell Impairment via Mitochondrial Dysregulation: Seok-Woo Hong, Jinmi Lee, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2018;33(3):403-412. Published online September 18, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.403

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Background

Emerging evidence suggests that sphingolipids may be involved in type 2 diabetes. However, the exact signaling defect through which disordered sphingolipid metabolism induces β-cell dysfunction remains unknown. The current study demonstrated that sphingosine-1-phosphate (S1P), the product of sphingosine kinase (SphK), is an essential factor for maintaining β-cell function and survival via regulation of mitochondrial action, as mediated by prohibitin (PHB).

Methods

We examined β-cell function and viability, as measured by mitochondrial function, in mouse insulinoma 6 (MIN6) cells in response to manipulation of cellular S1P and PHB levels.

Results

Lack of S1P induced by sphingosine kinase inhibitor (SphKi) treatment caused β-cell dysfunction and apoptosis, with repression of mitochondrial function shown by decreases in cellular adenosine triphosphate content, the oxygen consumption rate, the expression of oxidative phosphorylation complexes, the mitochondrial membrane potential, and the expression of key regulators of mitochondrial dynamics (mitochondrial dynamin-like GTPase [OPA1] and mitofusin 1 [MFN1]). Supplementation of S1P led to the recovery of mitochondrial function and greatly improved β-cell function and viability. Knockdown of SphK2 using small interfering RNA induced mitochondrial dysfunction, decreased glucose-stimulated insulin secretion (GSIS), and reduced the expression of PHB, an essential regulator of mitochondrial metabolism. PHB deficiency significantly reduced GSIS and induced mitochondrial dysfunction, and co-treatment with S1P did not reverse these trends.

Conclusion

Altogether, these data suggest that S1P is an essential factor in the maintenance of β-cell function and survival through its regulation of mitochondrial action and PHB expression.

Citations

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Thyroid
Prevalence and Annual Incidence of Thyroid Disease in Korea from 2006 to 2015: A Nationwide Population-Based Cohort Study: Hyemi Kwon, Jin-hyung Jung, Kyung-Do Han, Yong-Gyu Park, Jung-Hwan Cho, Da Young Lee, Ji Min Han, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2018;33(2):260-267. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.260

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Background

The incidence of thyroid nodules has increased worldwide in recent years. Thyroid dysfunction is a potential risk factor for hypercholesterolemia, cardiovascular disease, osteoporosis, arrhythmia, and neuropsychiatric disease. This study investigated the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism in Koreans.

Methods

In this nationwide population-based cohort study, 51,834,660 subjects were included using the National Health Information database from 2006 to 2015, after the exclusion of subjects with thyroid cancer.

Results

The prevalence in Korea in 2015 of thyroid nodules, hypothyroidism in patients taking thyroid hormone, and hyperthyroidism in patients undergoing treatment was 15.82/1,000 population, 15.94/1,000 population, and 2.76/1,000 population, respectively. All these diseases were more prevalent among women than among men. The number of incident cases of these three thyroid diseases steadily increased from 2006 to 2012, and then decreased through 2015. The incidence of thyroid nodules, hypothyroidism treated with thyroid hormone, and treated hyperthyroidism was 6.79/1,000 population, 1.76/1,000 population, and 0.55/1,000 population, respectively, in Korea in 2015. The use of methimazole continuously increased, from 33% of total antithyroid drug prescriptions in 2006 to 74.4% in 2015, and it became the most frequently prescribed antithyroid drug in Korea. In contrast, the use of propylthiouracil continuously decreased.

Conclusion

This was the first nationwide study of the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism to take into account recent changes and to include the current status of patients receiving treatment.

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Diabetes
Pioglitazone Attenuates Palmitate-Induced Inflammation and Endoplasmic Reticulum Stress in Pancreatic β-Cells: Seok-Woo Hong, Jinmi Lee, Jung Hwan Cho, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2018;33(1):105-113. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.105

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Background

The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear.

Methods

To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation.

Results

Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels.

Conclusion

Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus

Citations

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Diabetes
The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study: Yu Hyun Kwon, Seul-Ki Kim, Jung Hwan Cho, Hyemi Kwon, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2018;33(1):55-61. Published online January 30, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.55

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Background

Hypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time.

Methods

A total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal (<150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014.

Results

Among the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80).

Conclusion

In this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI.

Citations

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Diabetes Research and Clinical Practice.2024; 208: 111109. CrossRef
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Lipid Variability and Diabetes Mellitus
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Suranut Charoensri, Supatida Turnsaket, Chatlert Pongchaiyakul
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The Journal of Clinical Endocrinology & Metabolism.2019; 104(11): 5633. CrossRef
Response: The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study (Endocrinol Metab 2018;33:55–61, Yu Hyun Kwon et al.)
Eun-Jung Rhee, Yu Hyun Kwon
Endocrinology and Metabolism.2018; 33(3): 425. CrossRef
The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study (Endocrinol Metab 2018;33:55–61, Yu Hyun Kwon et al.)
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Thyroid
Comparison of Immunohistochemistry and Direct Sanger Sequencing for Detection of the BRAF^V600E Mutation in Thyroid Neoplasm: Hye-Seon Oh, Hyemi Kwon, Suyeon Park, Mijin Kim, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Jene Choi, Won Gu Kim, Dong Eun Song; Endocrinol Metab. 2018;33(1):62-69. Published online January 30, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.62

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Background

The BRAF^V600E mutation is the most common genetic alteration identified in papillary thyroid carcinoma (PTC). Because of its costs effectiveness and sensitivity, direct Sanger sequencing has several limitations. The aim of this study was to evaluate the efficiency of immunohistochemistry (IHC) as an alternative method to detect the BRAF^V600E mutation in preoperative and postoperative tissue samples.

Methods

We evaluated 71 patients who underwent thyroid surgery with the result of direct sequencing of the BRAF^V600E mutation. IHC staining of the BRAF^V600E mutation was performed in 49 preoperative and 23 postoperative thyroid specimens.

Results

Sixty-two patients (87.3%) had PTC, and of these, BRAF^V600E was confirmed by direct sequencing in 57 patients (91.9%). In 23 postoperative tissue samples, the BRAF^V600E mutation was detected in 16 samples (70%) by direct sequencing and 18 samples (78%) by IHC. In 24 fine needle aspiration (FNA) samples, BRAF^V600E was detected in 18 samples (75%) by direct sequencing and 16 samples (67%) by IHC. In 25 core needle biopsy (CNB) samples, the BRAF^V600E mutation was detected in 15 samples (60%) by direct sequencing and 16 samples (64%) by IHC. The sensitivity and specificity of IHC for detecting the BRAF^V600E mutation were 77.8% and 66.7% in FNA samples and 99.3% and 80.0% in CNB samples.

Conclusion

IHC could be an alternative method to direct Sanger sequencing for BRAF^V600E mutation detection both in postoperative and preoperative samples. However, application of IHC to detect the BRAF^V600E mutation in FNA samples is of limited value compared with direct sequencing.

Citations

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Circulating Nucleic Acids in Colorectal Cancer: Diagnostic and Prognostic Value
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Disease Markers.2024; 2024: 1. CrossRef
The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma
Xue-Jiao Xiong, Ming-Ming Xiao, Yi-Xia Zhang, Dong-Ge Liu, Mu-Lan Jin, Jian Wang, Hong-Tao Xu, Qing-Chang Li, Guang-Ping Wu, Giovanni Tuccari
Analytical Cellular Pathology.2023; 2023: 1. CrossRef
An effective approach for BRAF V600E mutation analysis of routine thyroid fine needle aspirates
Tanupriya Agrawal, Liqiang Xi, Winnifred Navarro, Mark Raffeld, Snehal B. Patel, Mark J. Roth, Joanna Klubo‐Gwiezdzinska, Armando C. Filie
Cytopathology.2022; 33(3): 344. CrossRef
A dual identification strategy based on padlock ligation and CRISPR/Cas14a for highly specific detection of BRAF V600E mutation in clinical samples
Weicheng Shi, Yao Gong, Decai Zhang, Tiantian Yang, Ming Yi, Jingyi Tan, Shijia Ding, Wei Cheng
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Research Progress of BRAF V600E Gene Mutation in Papillary Thyroid Carcinoma
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Advances in Clinical Medicine.2022; 12(09): 8499. CrossRef
VE1 immunohistochemistry is an adjunct tool for detection of BRAFV600E mutation: Validation in thyroid cancer patients
Faiza A. Rashid, Sobia Tabassum, Mosin S. Khan, Hifzur R. Ansari, Muhammad Asif, Ahmareen K. Sheikh, Syed Sameer Aga
Journal of Clinical Laboratory Analysis.2021;[Epub] CrossRef
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Changwen Jing, Haixia Cao, Rong Ma, Jianzhong Wu, Zhuo Wang
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Development of a Molecular Assay for Detection and Quantification of theBRAFVariation in Residual Tissue From Thyroid Nodule Fine-Needle Aspiration Biopsy Specimens
Guodong Fu, Ronald S. Chazen, Christina MacMillan, Ian J. Witterick
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L. Yu. Zurnadzhy, T.I. Rogounovitch, V.O. Saenko, M.Yu. Bolgov, S.V. Masiuk, S.V. Burko, T.L. Degtyaryova, S.V. Chernyshov, S.V. Gulevatyi, N. Mitsutake, M.D. Tronko, T.I. Bogdanova
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Tien Viet Tran, Kien Xuan Dang, Quynh Huong Pham, Ung Dinh Nguyen, Nhung Thi Trang Trinh, Luong Van Hoang, Son Anh Ho, Ba Van Nguyen, Duc Trong Nguyen, Dung Tuan Trinh, Dung Ngoc Tran, Arto Orpana, Ulf-Håkan Stenman, Jakob Stenman, Tho Huu Ho
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Cancers.2020; 12(3): 596. CrossRef
Comparison of Molecular Methods and BRAF Immunohistochemistry (VE1 Clone) for the Detection of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis
Kyle G. Parker, Michael G. White, Nicole A. Cipriani
Head and Neck Pathology.2020; 14(4): 1067. CrossRef
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Zhuo Wang, Changwen Jing, Haixia Cao, SiWen Liu, Jianzhong Wu, Rong Ma
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A Systematic Review and Meta-Analysis of the Diagnostic Performance of BRAF V600E Immunohistochemistry in Thyroid Histopathology
Ranjit Singarayer, Ozgur Mete, Laure Perrier, Lehana Thabane, Sylvia L. Asa, Stan Van Uum, Shereen Ezzat, David P. Goldstein, Anna M. Sawka
Endocrine Pathology.2019; 30(3): 201. CrossRef
Comparison of droplet digital PCR and direct Sanger sequencing for the detection of the BRAFV600E mutation in papillary thyroid carcinoma
Zhuo Wang, Kejing Sun, Changwen Jing, Haixia Cao, Rong Ma, Jianzhong Wu
Journal of Clinical Laboratory Analysis.2019;[Epub] CrossRef
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Narittee Sukswai, Joseph D. Khoury
Current Hematologic Malignancy Reports.2019; 14(5): 368. CrossRef
Immunohistochemistry is a feasible method to screen BRAF V600E mutation in colorectal and papillary thyroid carcinoma
Xiangyan Zhang, Lili Wang, Jigang Wang, Han Zhao, Jie Wu, Shuhong Liu, Lu Zhang, Yujun Li, Xiaoming Xing
Experimental and Molecular Pathology.2018; 105(1): 153. CrossRef

Clinical Study
Molecular Diagnosis Using Residual Liquid-Based Cytology Materials for Patients with Nondiagnostic or Indeterminate Thyroid Nodules: Hyemi Kwon, Won Gu Kim, Markus Eszlinger, Ralf Paschke, Dong Eun Song, Mijin Kim, Suyeon Park, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2016;31(4):586-591. Published online November 4, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.586

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Background

Molecular analysis for common somatic mutations in thyroid cancer can improve diagnostic accuracy of fine-needle aspiration cytology (FNAC) in the nondiagnostic or indeterminate category of thyroid nodules. In this study, we evaluated the feasibility of molecular diagnosis from residual liquid-based cytology (LBC) material after cytological diagnosis.

Methods

This prospective study enrolled 53 patients with thyroid nodules diagnosed as nondiagnostic, atypia of undetermined significance (AUS), or follicular lesion of undetermined significance (FLUS) after FNAC. DNAs and RNAs were isolated from residual LBC materials. BRAF^V600E and RAS point mutations, PAX8/peroxisome proliferator-activated receptor γ (PPARγ), RET/PTC1, and RET/PTC3 rearrangements were evaluated by real-time polymerase chain reaction and pyrosequencing.

Results

All DNAs from 53 residual LBC samples could be analysed and point mutations were detected in 10 samples (19%). In 17 AUS nodules, seven samples (41%) had point mutations including BRAF (n=4), NRAS (n=2), and KRAS (n=1). In 20 FLUS nodules, three samples (15%) had NRAS point mutations. RNA from only one FLUS nodule could be analysed for rearrangements and there was no abnormality.

Conclusion

Molecular analysis for BRAF and RAS mutations was feasible in residual LBC materials and might be useful for diagnosis of indeterminate thyroid nodules.

Citations

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Kras Gene Analysis Using Liquid-Based Cytology Specimens Predicts Therapeutic Responses and Prognosis in Patients with Pancreatic Cancer
Masahiro Itonaga, Reiko Ashida, Shin-Ichi Murata, Yasunobu Yamashita, Keiichi Hatamaru, Takashi Tamura, Yuki Kawaji, Yuudai Kayama, Tomoya Emori, Manabu Kawai, Hiroki Yamaue, Ibu Matsuzaki, Hirokazu Nagai, Yuichi Kinoshita, Ke Wan, Toshio Shimokawa, Masay
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From Traditional Histology to Next-Generation Pathology: A Review of The Workflow for the Characterisation and Molecular Profiling of Non-Small Cell Lung Cancer Samples

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Preanalytic variables in quality and quantity of nucleic acids extracted from FNA specimens of thyroid gland nodules collected in CytoLyt: Cellularity and storage time
Jonas J. Heymann, Lorene M. Yoxtheimer, Hyeon Jin Park, Evan M. Fernandez, Kirk E. Facey, Susan A. Alperstein, Hung V. Tran, Inji Baek, Theresa Scognamiglio, Hanna Rennert, Momin T. Siddiqui, Wei Song
Cancer Cytopathology.2020; 128(9): 656. CrossRef
Diagnostic accuracy of molecular testing with three molecular markers on thyroid fine‐needle aspiration cytology with abnormal category
Hatice Seneldir, Gozde Kir, Tuce Soylemez, Rabia B. Girgin, Nurver Ozbay, Filiz Ozen, Handan Ankarali, Gurhan Bas, Orhan Alimoglu
Diagnostic Cytopathology.2020; 48(6): 507. CrossRef
Small but powerful: the promising role of small specimens for biomarker testing
Qiong Gan, Sinchita Roy-Chowdhuri
Journal of the American Society of Cytopathology.2020; 9(5): 450. CrossRef
Centrifuged supernatants from FNA provide a liquid biopsy option for clinical next‐generation sequencing of thyroid nodules
Wenrui Ye, Brette Hannigan, Stephanie Zalles, Meenakshi Mehrotra, Bedia A. Barkoh, Michelle D. Williams, Maria E. Cabanillas, Beth Edeiken‐Monroe, Peter Hu, Dzifa Duose, Ignacio I. Wistuba, L. Jeffrey Medeiros, John Stewart, Rajyalakshmi Luthra, Sinchita
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K-ras mutation analysis of residual liquid-based cytology specimens from endoscopic ultrasound-guided fine needle aspiration improves cell block diagnosis of pancreatic ductal adenocarcinoma
Yoko Sekita-Hatakeyama, Takeshi Nishikawa, Mao Takeuchi, Kouhei Morita, Maiko Takeda, Kinta Hatakeyama, Tokiko Nakai, Tomoko Uchiyama, Hiroe Itami, Tomomi Fujii, Akira Mitoro, Masayuki Sho, Chiho Ohbayashi, Giancarlo Troncone
PLOS ONE.2018; 13(3): e0193692. CrossRef
Comparison of Immunohistochemistry and Direct Sanger Sequencing for Detection of theBRAFV600EMutation in Thyroid Neoplasm
Hye-Seon Oh, Hyemi Kwon, Suyeon Park, Mijin Kim, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Jene Choi, Won Gu Kim, Dong Eun Song
Endocrinology and Metabolism.2018; 33(1): 62. CrossRef
Next-Generation Sequencing Identifies Gene Mutations That Are Predictive of Malignancy in Residual Needle Rinses Collected From Fine-Needle Aspirations of Thyroid Nodules
Maren Y. Fuller, Dina Mody, April Hull, Kristi Pepper, Heather Hendrickson, Randall Olsen
Archives of Pathology & Laboratory Medicine.2018; 142(2): 178. CrossRef
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Won-Young Lee
Endocrinology and Metabolism.2017; 32(1): 62. CrossRef
Loss of c-KIT expression in thyroid cancer cells
Sara Franceschi, Francesca Lessi, Federica Panebianco, Elena Tantillo, Marco La Ferla, Michele Menicagli, Paolo Aretini, Alessandro Apollo, Antonio Giuseppe Naccarato, Ivo Marchetti, Chiara Maria Mazzanti, Aamir Ahmad
PLOS ONE.2017; 12(3): e0173913. CrossRef

Clinical Study
Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease: Hyemi Kwon, Won Gu Kim, Eun Kyung Jang, Mijin Kim, Suyeon Park, Min Ji Jeon, Tae Yong Kim, Jin-Sook Ryu, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2016;31(2):300-310. Published online April 25, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.300

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Background

Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse.

Methods

This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal.

Results

Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%.

Conclusion

TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Citations

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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
Thyroid-Stimulatory Antibody as a Predictive Factor for Graves’ Disease Relapse
Tiago Da Silva Santos, José Carlos Oliveira, Cláudia Freitas, André Couto de Carvalho
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The Prediction Model Using Thyroid-stimulating Immunoglobulin Bioassay For Relapse of Graves’ Disease
Han-Sang Baek, Jaejun Lee, Chai-Ho Jeong, Jeongmin Lee, Jeonghoon Ha, Kwanhoon Jo, Min-Hee Kim, Jae Hyoung Cho, Moo Il Kang, Dong-Jun Lim
Journal of the Endocrine Society.2022;[Epub] CrossRef
Identification of patients with Graves’ disease who benefit from high-dose radioactive iodine therapy
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Xinxin Zhu, Yaguang Zhang, Xiaoyu Zhao, Xiaona Zhang, Zixuan Ru, Yanmeizhi Wu, Xu Yang, Boyu Hou, Hong Qiao
Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef
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Endocrinology and Metabolism.2021; 36(3): 491. CrossRef
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Yulin Zhou, Mengxi Zhou, Yicheng Qi, Weiqing Wang, Xinxin Chen, Shu Wang
Therapeutic Advances in Endocrinology and Metabolism.2021; 12: 204201882110449. CrossRef
Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy
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Wilmar M. Wiersinga
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Hyun-Kyung Chung
International Journal of Thyroidology.2019; 12(2): 79. CrossRef
When should antithyroid drug therapy to reduce the relapse rate of hyperthyroidism in Graves’ disease be discontinued?
Suyeon Park, Eyun Song, Hye-Seon Oh, Mijin Kim, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Doo Man Kim, Won Bae Kim
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The Journal of Clinical Endocrinology & Metabolism.2017; 102(6): 1917. CrossRef
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Clinical Study
Low Prevalence of Somatic TERT Promoter Mutations in Classic Papillary Thyroid Carcinoma: Min Ji Jeon, Won Gu Kim, Soyoung Sim, Seonhee Lim, Hyemi Kwon, Tae Yong Kim, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2016;31(1):100-104. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.100

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Background

Transcriptional activating mutations of telomerase reverse transcriptase (TERT) are associated with more aggressive thyroid cancer. We evaluated the significance of TERT promoter mutations in Korean patients with classic papillary thyroid cancer (PTC).

Methods

Genomic DNA was isolated from four thyroid cancer cell lines and 35 fresh-frozen PTC tissues. TERT promoter mutations (C228T and C250T) and the BRAF V600E mutation were evaluated by polymerase chain reaction amplification and direct sequencing.

Results

The CC228229TT mutation in the TERT promoter was detected in BCPAP cells and the C250T mutation was found in 8505C cells. No TERT promoter mutation was observed in Cal-62 or ML-1 cells. The C228T mutation was found in only 1 of 35 (2.8%) PTCs and no C250T mutations were detected in any of the study subjects. The BRAF V600E mutation was found in 20 of 35 (57.1%) PTCs. One patient with the C228T TERT mutation also harbored the BRAF V600E mutation and developed a recurrence.

Conclusion

The prevalence of somatic TERT promoter mutations was low in Korean patients with classic PTC. Therefore, the prognostic role of TERT promoter mutations might be limited in this patient cohort.

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Clinical Study
Thyrotoxic Periodic Paralysis and Polymorphisms of the ADRB2, AR, and GABRA3 Genes in Men with Graves Disease: Suyeon Park, Tae Yong Kim, Soyoung Sim, Seonhee Lim, Mijin Kim, Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2016;31(1):142-146. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.142

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Background

Thyrotoxic periodic paralysis (TPP) is a rare complication of thyrotoxicosis characterized by acute attacks of muscle weakness and hypokalemia. Recently, variation in several genes was suggested to be associated with TPP. This study evaluated the genetic predisposition to TPP in terms of the β2-adrenergic receptor (ADRB2), androgen receptor (AR), and γ-aminobutyric acid receptor α3 subunit (GABRA3) genes.

Methods

This study enrolled 48 men with Graves disease (GD) and TPP, and 48 GD patients without TPP. We compared the frequencies of candidate polymorphisms between the two groups.

Results

The frequency of the Gly16/Gly16 genotype in ADRB2 was not significantly associated with TPP (P=0.32). More CAG repeats (≥26) in the AR gene were not correlated with TPP (odds ratio [OR], 2.46; 95% confidence interval [CI], 0.81 to 8.09; P=0.08). The allele frequency of the TT genotype in the GABRA3 gene was not associated with TPP (OR, 1.83; 95% CI, 0.54 to 6.74; P=0.41).

Conclusion

The polymorphisms in the ADRB2, AR, and GABRA3 genes could not explain the genetic susceptibility to TPP in Korean men with GD.

Citations

Citations to this article as recorded by

RNASET2,GPR174, and PTPN22 gene polymorphisms are related to the risk of liver damage associated with the hyperthyroidism in patients with Graves’ disease
Qing Zhang, Shaozheng Liu, Yanxing Guan, Qingjie Chen, Qing Zhang, Xiang Min
Journal of Clinical Laboratory Analysis.2018;[Epub] CrossRef
Articles inEndocrinology and Metabolismin 2016
Won-Young Lee
Endocrinology and Metabolism.2017; 32(1): 62. CrossRef
Periodic Paralysis and Encephalopathy as Initial Manifestations of Graves’ Disease
Theocharis Tsironis, Athanasios Tychalas, Dimitrios Kiourtidis, Jannis Kountouras, Georgia Xiromerisiou, Jobst Rudolf, Georgia Deretzi
The Neurologist.2017; 22(4): 134. CrossRef
Thyrotoxic periodic paralysis
Zdeněk Doležel, Dana Novotná, Helena Schneiderová, Jan Papež, Martin Jouza
Pediatrie pro praxi.2016; 17(6): 379. CrossRef

Thyroid
Lack of Associations between Body Mass Index and Clinical Outcomes in Patients with Papillary Thyroid Carcinoma: Hyemi Kwon, Mijin Kim, Yun Mi Choi, Eun Kyung Jang, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Dong Eun Song, Jung Hwan Baek, Suck Joon Hong, Won Bae Kim; Endocrinol Metab. 2015;30(3):305-311. Published online November 26, 2014; DOI: https://doi.org/10.3803/EnM.2015.30.3.305

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Background

Obesity is associated with aggressive pathological features and poor clinical outcomes in breast and prostate cancers. In papillary thyroid carcinoma (PTC), these relationships remain still controversial. This study aimed to evaluate the associations between body mass index (BMI) and the clinical outcomes of patients with PTC.

Methods

This retrospective study included 1,189 patients who underwent total thyroidectomy for PTCs equal to or larger than 1 cm in size. Clinical outcomes were evaluated and compared based on the BMI quartiles.

Results

There were no significant associations between BMI quartiles and primary tumor size, extrathyroidal invasion, cervical lymph node metastasis, or distant metastasis. However, an increase in mean age was associated with an increased BMI (P for trend <0.001). Multifocality and advanced tumor-node-metastasis (TNM) stage (stage III or IV) were significantly associated with increases of BMI (P for trend 0.02 and <0.001, respectively). However, these associations of multifocality and advanced TNM stage with BMI were not significant in multivariate analyses adjusted for age and gender. Moreover, there were no differences in recurrence-free survivals according to BMI quartiles (P=0.26).

Conclusion

In the present study, BMI was not associated with the aggressive clinicopathological features or recurrence-free survivals in patients with PTC.

Citations

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A Data-Driven Approach to Refine Predictions of Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study
Giorgio Grani, Michele Gentili, Federico Siciliano, Domenico Albano, Valentina Zilioli, Silvia Morelli, Efisio Puxeddu, Maria Chiara Zatelli, Irene Gagliardi, Alessandro Piovesan, Alice Nervo, Umberto Crocetti, Michela Massa, Maria Teresa Samà, Chiara Mel
The Journal of Clinical Endocrinology & Metabolism.2023; 108(8): 1921. CrossRef
Potential impact of obesity on the aggressiveness of low- to intermediate-risk papillary thyroid carcinoma: results from a MASTER cohort study
Mijin Kim, Yae Eun Kang, Young Joo Park, Bon Seok Koo, Eu Jeong Ku, June Young Choi, Eun Kyung Lee, Bo Hyun Kim
Endocrine.2023; 82(1): 134. CrossRef
Potential Impact of Body Mass Index on the Clinical Outcome of Papillary Thyroid Cancer After High-Dose Radioactive Iodine Therapy
Jingjia Cao, Xiaolu Zhu, Yaru Sun, Xiao Li, Canhua Yun, Wei Zhang
Frontiers in Endocrinology.2022;[Epub] CrossRef
Nutritional status and follicular-derived thyroid cancer: An update
Luigi Barrea, Marco Gallo, Rosaria Maddalena Ruggeri, Paola Di Giacinto, Franz Sesti, Natalie Prinzi, Valerio Adinolfi, Viola Barucca, Valerio Renzelli, Giovanna Muscogiuri, Annamaria Colao, Roberto Baldelli
Critical Reviews in Food Science and Nutrition.2021; 61(1): 25. CrossRef
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Onur Elbasan, Dilek Gogas Yavuz
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Association of BMI with Clinicopathological Features of Papillary Thyroid Cancer: A Systematic Review and Meta‐Analysis
R. J. O'Neill, S. Abd Elwahab, M. J. Kerin, A. J. Lowery
World Journal of Surgery.2021; 45(9): 2805. CrossRef
Association Between Aggressive Clinicopathologic Features of Papillary Thyroid Carcinoma and Body Mass Index: A Systematic Review and Meta-Analysis
Aliki Economides, Konstantinos Giannakou, Ioannis Mamais, Panayiotis A. Economides, Panagiotis Papageorgis
Frontiers in Endocrinology.2021;[Epub] CrossRef
Potential Impact of BMI on the Aggressiveness of Presentation and Clinical Outcome of Differentiated Thyroid Cancer
Antonio Matrone, Giovanni Ceccarini, Marianna Beghini, Federica Ferrari, Carla Gambale, Mariaida D’Aqui, Paolo Piaggi, Liborio Torregrossa, Eleonora Molinaro, Fulvio Basolo, Paolo Vitti, Ferruccio Santini, Rossella Elisei
The Journal of Clinical Endocrinology & Metabolism.2020; 105(4): e1124. CrossRef
Correlation between obesity and clinicopathological characteristics in patients with papillary thyroid cancer: a study of 1579 cases: a retrospective study
Huijuan Wang, Pingping Wang, Yu Wu, Xiukun Hou, Zechun Peng, Weiwei Yang, Lizhao Guan, Linfei Hu, Jingtai Zhi, Ming Gao, Xiangqian Zheng
PeerJ.2020; 8: e9675. CrossRef
Lack of association between obesity and aggressiveness of differentiated thyroid cancer
G. Grani, L. Lamartina, T. Montesano, G. Ronga, V. Maggisano, R. Falcone, V. Ramundo, L. Giacomelli, C. Durante, D. Russo, M. Maranghi
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Mitochondrial DNA haplogroup K as a contributor to protection against thyroid cancer in a population from southeast Europe
Relu Cocoş, Sorina Schipor, Corin Badiu, Florina Raicu
Mitochondrion.2018; 39: 43. CrossRef
The impact of BMI on clinical progress, response to treatment, and disease course in patients with differentiated thyroid cancer
Danuta Gąsior-Perczak, Iwona Pałyga, Monika Szymonek, Artur Kowalik, Agnieszka Walczyk, Janusz Kopczyński, Katarzyna Lizis-Kolus, Tomasz Trybek, Estera Mikina, Dorota Szyska-Skrobot, Klaudia Gadawska-Juszczyk, Stefan Hurej, Artur Szczodry, Anna Słuszniak,
PLOS ONE.2018; 13(10): e0204668. CrossRef
Pretreatment BMI Is Associated with Aggressive Clinicopathological Features of Papillary Thyroid Carcinoma: A Multicenter Study
Shi-tong Yu, Wanzhi Chen, Qian Cai, Faya Liang, Debin Xu, Ping Han, Jichun Yu, Xiaoming Huang
International Journal of Endocrinology.2017; 2017: 1. CrossRef
Associations between body mass index and lymph node metastases of patients with papillary thyroid cancer
Changhua Wu, Liang Wang, Wanjun Chen, Shujuan Zou, Aiju Yang
Medicine.2017; 96(9): e6202. CrossRef

Thyroid
Erratum: Figure Correction: Standardized Thyroid Cancer Mortality in Korea between 1985 and 2010: Yun Mi Choi, Tae Yong Kim, Eun Kyung Jang, Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2015;30(1):116. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.116

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Thyroid
Standardized Thyroid Cancer Mortality in Korea between 1985 and 2010: Yun Mi Choi, Tae Yong Kim, Eun Kyung Jang, Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2014;29(4):530-535. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.530

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Background

The prevalence of thyroid cancer has increased very rapidly in Korea. However, there is no published report focusing on thyroid cancer mortality in Korea. In this study, we aimed to evaluate standardized thyroid cancer mortality using data from Statistics Korea (the Statistical Office of Korea).

Methods

Population and mortality data from 1985 to 2010 were obtained from Statistics Korea. Age-standardized rates of thyroid cancer mortality were calculated according to the standard population of Korea, as well as World Health Organization (WHO) standard population and International Cancer Survival Standard (ICSS) population weights.

Results

The crude thyroid cancer mortality rate increased from 0.1 to 0.7 per 100,000 between 1985 and 2010. The pattern was the same for both sexes. The age-standardized mortality rate (ASMR) for thyroid cancer for Korean resident registration population increased from 0.19 to 0.67 between 1985 and 2000. However, it decreased slightly, from 0.67 to 0.55, between 2000 and 2010. When mortality was adjusted using the WHO standard population and ICSS population weights, the ASMR similarly increased until 2000, and then decreased between 2000 and 2010.

Conclusion

Thyroid cancer mortality increased until 2000 in Korea. It started to decrease from 2000.

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Thyroid
Solitary Skin Metastasis of Papillary Thyroid Carcinoma: Hyemi Kwon, Hyojung Kim, Sojung Park, Dong Eun Song, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2014;29(4):579-583. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.579

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A solitary skin metastasis is a rare manifestation of papillary thyroid carcinoma (PTC). A 55-year-old woman presented with a movable subcutaneous nodule in her anterior neck for several months. Three years ago, she underwent total thyroidectomy and remnant ablation for classical PTC (pT3N0M0) and was under thyroxine suppression therapy without any evidence of recurrent disease. The subcutaneous nodule was 0.4 cm in size, firm, and movable without any change in the overlying skin. Recurrent PTC was confirmed after excision biopsy. Eight months after, she got a new nodule along the previous excision site. After punch biopsy, metastatic PTC was confirmed in the deep dermis and was re-excised with a clear resection margin. This is the first report of a case of solitary skin metastasis of PTC in Korea. Although solitary skin metastasis of PTC is rare, it should be considered in patients with a skin nodule.

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Author index