Endocrinology and Metabolism

Review Articles

Thyroid
Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines: Min Joo Kim, Jae Hoon Moon, Eun Kyung Lee, Young Shin Song, Kyong Yeun Jung, Ji Ye Lee, Ji-hoon Kim, Kyungsik Kim, Sue K. Park, Young Joo Park; Endocrinol Metab. 2024;39(1):47-60. Published online February 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.1937

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Abstract PDF PubReader ePub: The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Thyroid
Novel and Advanced Ultrasound Techniques for Thyroid Thermal Ablation: Wai-Kin Chan, Jui-Hung Sun, Miaw-Jene Liou, Chia-Jung Hsu, Yu-Ling Lu, Wei-Yu Chou, Yan-Rong Li, Feng-Hsuan Liu; Endocrinol Metab. 2024;39(1):40-46. Published online February 13, 2024; DOI: https://doi.org/10.3803/EnM.2024.1917

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Abstract PDF PubReader ePub: Thyroid radiofrequency ablation and microwave ablation are widely adopted minimally invasive treatments for diverse thyroid conditions worldwide. Fundamental skills such as the trans-isthmic approach and the moving shot technique are crucial for performing thyroid ablation, and advanced techniques, including hydrodissection and vascular ablation, improve safety and efficacy and reduce complications. Given the learning curve associated with ultrasound-guided therapeutic procedures, operators need training and experience. While training models exist, limited attention has been given to ultrasound maneuvers in ablation needle manipulation. This article introduces two essential maneuvers, the zigzag moving technique and the alienate maneuver, while also reviewing the latest ultrasound techniques in thyroid ablation, contributing valuable insights into this evolving field.

Diabetes, obesity and metabolism
Glucagon: Physiological and Pharmacological Functions and Pathophysiological Significance in Type 2 Diabetes: Tadahiro Kitamura; Endocrinol Metab. 2024;39(1):33-39. Published online February 22, 2024; DOI: https://doi.org/10.3803/EnM.2024.1911

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Abstract PDF PubReader ePub: Glucagon has many functions, including the promotion of hepatic glucose production, fatty acid oxidation, thermogenesis, energy consumption, lipolysis, and myocardial contraction, as well as the suppression of lipogenesis, appetite, and gastrointestinal motility. However, it remains unclear which of these functions are physiological and which are pharmacological. Research on glucagon has lagged behind research on insulin because cross-reactivity with glucagon-related peptides in plasma has hindered the development of an accurate measurement system for glucagon. We recently developed a new glucagon sandwich enzyme-linked immunosorbent assay (ELISA) that is more specific and more sensitive to glucagon than the currently used measurement systems. The new sandwich ELISA is expected to contribute to personalized medicine for diabetes through its use in clinical examinations, the diagnosis of the pathophysiological condition of individual diabetes patients, and the choice of a treatment strategy. Efforts are continuing to develop glucagon/glucagon-like peptide-1 receptor dual agonists to improve obesity and fatty liver by enhancing glucagon’s appetite-suppressing and lipolysis- and thermogenesis-promoting effects. Thus, glucagon is expected to be applied to new diagnostic and therapeutic strategies based on a more accurate understanding of its functions.

Diabetes, obesity and metabolism
Initial Combination Therapy in Type 2 Diabetes: Ji Yoon Kim, Nam Hoon Kim; Endocrinol Metab. 2024;39(1):23-32. Published online November 30, 2023; DOI: https://doi.org/10.3803/EnM.2023.1816

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Abstract PDF PubReader ePub: Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial for preventing diabetes-related complications. Previous studies showed that monotherapy with a stepwise add-on approach was seldom effective for long-term durable glycemic control. Combination therapy, which refers to the use of two or more drugs to control hyperglycemia, has multiple benefits, including the ability to target a variety of pathophysiological processes underlying hyperglycemia. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach. Emerging evidence indicates that initial combination therapy is associated with preserved β-cell function and fewer complications in T2D. However, cost-effectiveness and adverse events with combination therapy are issues that should be considered. Therefore, initial combination therapy is an important option for patients with T2D that clinicians should consider with a view toward balancing benefits and potential harms. In this review, we summarize the literature addressing initial combination therapy in T2D, and we suggest optimal strategies based on clinical situations and patient characteristics.

Diabetes, obesity and metabolism
The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update: Agnieszka Jakubowska, Carel W. le Roux, Adie Viljoen; Endocrinol Metab. 2024;39(1):12-22. Published online February 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.1942

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Abstract PDF PubReader ePub

Obesity is the fifth leading risk factor for global deaths with numbers continuing to increase worldwide. In the last 20 years, the emergence of pharmacological treatments for obesity based on gastrointestinal hormones has transformed the therapeutic landscape. The successful development of glucagon-like peptide-1 (GLP-1) receptor agonists, followed by the synergistic combined effect of glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists achieved remarkable weight loss and glycemic control in those with the diseases of obesity and type 2 diabetes. The multiple cardiometabolic benefits include improving glycemic control, lipid profiles, blood pressure, inflammation, and hepatic steatosis. The 2023 phase 2 double-blind, randomized controlled trial evaluating a GLP-1/GIP/glucagon receptor triagonist (retatrutide) in patients with the disease of obesity reported 24.2% weight loss at 48 weeks with 12 mg retatrutide. This review evaluates the current available evidence for GLP-1 receptor agonists, dual GLP-1/GIP receptor co-agonists with a focus on GLP-1/GIP/glucagon receptor triagonists and discusses the potential future benefits and research directions.

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New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review
Jorge E. Jalil, Luigi Gabrielli, María Paz Ocaranza, Paul MacNab, Rodrigo Fernández, Bruno Grassi, Paulina Jofré, Hugo Verdejo, Monica Acevedo, Samuel Cordova, Luis Sanhueza, Douglas Greig
International Journal of Molecular Sciences.2024; 25(8): 4407. CrossRef

Namgok Lecture 2023

Diabetes, obesity and metabolism
Hypothalamic AMP-Activated Protein Kinase as a Whole-Body Energy Sensor and Regulator: Se Hee Min, Do Kyeong Song, Chan Hee Lee, Eun Roh, Min-Seon Kim; Endocrinol Metab. 2024;39(1):1-11. Published online February 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.1922

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Abstract PDF PubReader ePub: 5´-Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a cellular energy sensor, is an essential enzyme that helps cells maintain stable energy levels during metabolic stress. The hypothalamus is pivotal in regulating energy balance within the body. Certain neurons in the hypothalamus are sensitive to fluctuations in food availability and energy stores, triggering adaptive responses to preserve systemic energy equilibrium. AMPK, expressed in these hypothalamic neurons, is instrumental in these regulatory processes. Hypothalamic AMPK activity is modulated by key metabolic hormones. Anorexigenic hormones, including leptin, insulin, and glucagon-like peptide 1, suppress hypothalamic AMPK activity, whereas the hunger hormone ghrelin activates it. These hormonal influences on hypothalamic AMPK activity are central to their roles in controlling food consumption and energy expenditure. Additionally, hypothalamic AMPK activity responds to variations in glucose concentrations. It becomes active during hypoglycemia but is deactivated when glucose is introduced directly into the hypothalamus. These shifts in AMPK activity within hypothalamic neurons are critical for maintaining glucose balance. Considering the vital function of hypothalamic AMPK in the regulation of overall energy and glucose balance, developing chemical agents that target the hypothalamus to modulate AMPK activity presents a promising therapeutic approach for metabolic conditions such as obesity and type 2 diabetes mellitus.

Brief Report

Diabetes, obesity and metabolism
Partial Deletion of Perk Improved High-Fat Diet-Induced Glucose Intolerance in Mice: Jooyeop Lee, Min Joo Kim, Seoil Moon, Ji Yoon Lim, Kyong Soo Park, Hye Seung Jung; Endocrinol Metab. 2023;38(6):782-787. Published online November 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1738

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Abstract PDF Supplementary Material PubReader ePub: Although pancreatic endoplasmic reticulum kinase (PERK) is indispensable to beta cells, low-dose PERK inhibitor improved glucose- stimulated insulin secretion (GSIS) and hyperglycemia in diabetic mice. Current study examined if partial deletion of Perk (Perk^+/-) recapitulated the effects of PERK inhibitor, on the contrary to the complete deletion. Perk^+/- mice and wild-type controls were fed with a high-fat diet (HFD) for 23 weeks. Glucose tolerance was evaluated along with serum insulin levels and islet morphology. Perk^+/- mice on normal chow were comparable to wild-type mice in various metabolic features. HFD-induced obesity was not influenced by Perk reduction; however, HFD-induced glucose intolerance was significantly improved since 15-week HFD. HFD-induced compromises in GSIS were relieved by Perk reduction, accompanied by reductions in phosphorylated PERK and activating transcription factor 4 (ATF4) in the islets. Meanwhile, HFD-induced islet expansion was not significantly affected. In summary, partial deletion of Perk improved glucose tolerance and GSIS impaired by diet-induced obesity, without changes in body weights or islet mass.

Original Articles

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

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

Miscellaneous
AM1638, a GPR40-Full Agonist, Inhibited Palmitate- Induced ROS Production and Endoplasmic Reticulum Stress, Enhancing HUVEC Viability in an NRF2-Dependent Manner: Hwan-Jin Hwang, Joo Won Kim, SukHwan Yun, Min Jeong Park, Eyun Song, Sooyeon Jang, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo; Endocrinol Metab. 2023;38(6):760-769. Published online November 2, 2023; DOI: https://doi.org/10.3803/EnM.2023.1774

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Abstract PDF PubReader ePub: Background
G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress.
Methods
Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium.
Results
In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2–related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. We also found that palmitate-induced CCAAT/enhancer‐binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner.
Conclusion
GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis.

Miscellaneous
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; Endocrinol Metab. 2023;38(6):750-759. Published online November 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1785

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Abstract PDF Supplementary Material PubReader ePub: Background
This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs.
Methods
We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published.
Results
A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone.
Conclusion
Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.

Thyroid
Phospholipase C-γ as a Potential Therapeutic Target for Graves’ Orbitopathy: Tae Hoon Roh, Min Kyung Chae, Jae Sang Ko, Don O. Kikkawa, Sun Young Jang, Jin Sook Yoon; Endocrinol Metab. 2023;38(6):739-749. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1780

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Abstract PDF Supplementary Material PubReader ePub: Background
Phospholipase C-γ (PLC-γ) plays a crucial role in immune responses and is related to the pathogenesis of various inflammatory disorders. In this study, we investigated the role of PLC-γ and the therapeutic effect of the PLC-specific inhibitor U73122 using orbital fibroblasts from patients with Graves’ orbitopathy (GO).
Methods
The expression of phospholipase C gamma 1 (PLCG1) and phospholipase C gamma 2 (PLCG2) was evaluated using polymerase chain reaction in GO and normal orbital tissues/fibroblasts. The primary cultures of orbital fibroblasts were treated with non-toxic concentrations of U73122 with or without interleukin (IL)-1β to determine its therapeutic efficacy. The proinflammatory cytokine levels and activation of downstream signaling molecules were determined using Western blotting.
Results
PLCG1 and PLCG2 mRNA expression was significantly higher in GO orbital tissues than in controls (P<0.05). PLCG1 and PLCG2 mRNA expression was significantly increased (P<0.05) in IL-1β, tumor necrosis factor-α, and a cluster of differentiation 40 ligand-stimulated GO fibroblasts. U73122 significantly inhibited the IL-1β-induced expression of proinflammatory molecules, including IL-6, IL-8, monocyte chemoattractant protein-1, cyclooxygenase-2, and intercellular adhesion molecule-1 (ICAM-1), and phosphorylated protein kinase B (p-Akt) and p38 (p-p38) kinase in GO fibroblasts, whereas it inhibited IL-6, IL-8, and ICAM-1, and p-Akt and c-Jun N-terminal kinase (p-JNK) in normal fibroblasts (P<0.05).
Conclusion
PLC-γ-inhibiting U73122 suppressed the production of proinflammatory cytokines and the phosphorylation of Akt and p38 kinase in GO fibroblasts. This study indicates the implications of PLC-γ in GO pathogenesis and its potential as a therapeutic target for GO.

Thyroid
Exploring the Association between Thyroid Function and Frailty: Insights from Representative Korean Data: Youn-Ju Lee, Min-Hee Kim, Dong-Jun Lim, Jung-Min Lee, Sang Ah Chang, Jeongmin Lee; Endocrinol Metab. 2023;38(6):729-738. Published online November 2, 2023; DOI: https://doi.org/10.3803/EnM.2023.1769

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Background
This study investigates the association between thyroid function and frailty in the old patients using representative data.
Methods
The study was conducted using data from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. The study population included 2,416 participants aged 50 years and older with available thyroid function test data. Frailty assessment was performed using the Fried frailty phenotype. The prevalence of frailty was analyzed across different thyroid diseases and thyroid function parameters.
Results
The significant association between thyroid dysfunction and frailty was observed in overt hyperthyroidism and subclinical hyperthyroidism. After adjusting for various factors, the association between thyroid dysfunction and frailty remained significant. On the other hand, overt hypothyroidism did not show a significant association with frailty in the adjusted analysis. For individuals with overt hyperthyroidism and subclinical hyperthyroidism, higher levels of free thyroxine (FT4) were significantly associated with an increased risk of frailty (aOR >999; 95% CI, >999 to 999). Among individuals with overt hypothyroidism, lower level of FT4 levels and high thyrotropin (TSH) levels showed a significant association with frailty risk (FT4: aOR, <0.01; TSH: aOR, 999). In participants with subclinical hypothyroidism, there were no significant associations between parameters for thyroid and frailty risk.
Conclusion
These findings suggest that thyroid dysfunction, particularly overt hyperthyroidism and subclinical hyperthyroidism, may be associated with an increased risk of frailty in the old patients.

Citations

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Associations of thyroid feedback quantile-based index with diabetes in euthyroid adults in the United States and China
Heng Wan, Genfeng Yu, Yajun He, Siyang Liu, Xingying Chen, Yuqi Jiang, Hualin Duan, Xu Lin, Lan Liu, Jie Shen
Annals of Medicine.2024;[Epub] CrossRef

Thyroid
Comparative Analysis of Driver Mutations and Transcriptomes in Papillary Thyroid Cancer by Region of Residence in South Korea: Jandee Lee, Seonhyang Jeong, Hwa Young Lee, Sunmi Park, Meesson Jeong, Young Suk Jo; Endocrinol Metab. 2023;38(6):720-729. Published online November 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1758

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Abstract PDF Supplementary Material PubReader ePub: Background
Radiation exposure is a well-known risk factor for papillary thyroid cancer (PTC). South Korea has 24 nuclear reactors in operation; however, no molecular biological analysis has been performed on patients with PTC living near nuclear power plants.
Methods
We retrospectively included patients with PTC (n=512) divided into three groups according to their place of residence at the time of operation: inland areas (n=300), coastal areas far from nuclear power plants (n=134), and nuclear power plant areas (n=78). After propensity score matching (1:1:1) by age, sex, and surgical procedure, the frequency of representative driver mutations and gene expression profiles were compared (n=50 per group). Epithelial-mesenchymal transition (EMT), BRAF, thyroid differentiation, and radiation scores were calculated and compared.
Results
No significant difference was observed in clinicopathological characteristics, including radiation exposure history and the frequency of incidentally discovered thyroid cancer, among the three groups. BRAF^V600E mutation was most frequently detected in the groups, with no difference among the three groups. Furthermore, gene expression profiles showed no statistically significant difference. EMT and BRAF scores were higher in our cohort than in cohorts from Chernobyl tissue bank and The Cancer Genome Atlas Thyroid Cancer; however, there was no difference according to the place of residence. Radiation scores were highest in the Chernobyl tissue bank but exhibited no difference according to the place of residence.
Conclusion
Differences in clinicopathological characteristics, frequency of representative driver mutations, and gene expression profiles were not observed according to patients’ region of residence in South Korea.

Calcium & bone metabolism
Familial Correlation and Heritability of Hand Grip Strength in Korean Adults (Korea National Health and Nutrition Examination Survey 2014 to 2019): Seong Hee Ahn, Eun Byeol Park, Seongha Seo, Yongin Cho, Da Hea Seo, So Hun Kim, Young Ju Suh, Seongbin Hong; Endocrinol Metab. 2023;38(6):709-719. Published online November 7, 2023; DOI: https://doi.org/10.3803/EnM.2023.1740

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Abstract PDF Supplementary Material PubReader ePub: Background
The onset and progression of sarcopenia are highly variable among individuals owing to genetic and environmental factors. However, there are a limited number of studies measuring the heritability of muscle strength in large numbers of parent-adult offspring pairs. We aimed to investigate the familial correlation and heritability of hand grip strength (HGS) among Korean adults.
Methods
This family-based cohort study on data from the Korea National Health and Nutrition Examination Survey (2014 to 2019) included 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations of HGS were calculated in different pairs of relatives. Variance component methods were used to estimate heritability.
Results
The heritability estimate of HGS among Korean adults was 0.154 (standard error, 0.066). Correlation coefficient estimates for HGS between parent-offspring, sibling, and spouse pairs were significant at 0.07, 0.10, and 0.23 (P<0.001, P=0.041, and P<0.001, respectively). The total variance in the HGS phenotype was explained by additive genetic (15.4%), shared environmental (11.0%), and unique environmental (73.6%) influences. The odds of weak HGS significantly increased in the offspring of parents with weak HGS (odds ratio [OR], 1.69–3.10; P=0.027–0.038), especially in daughters (OR, 2.04–4.64; P=0.029–0.034).
Conclusion
HGS exhibits a familial correlation and significant heritable tendency in Korean adults. Therefore, Asian adults, especially women, who have parents with weak HGS, need to pay special attention to their muscle health with the help of healthy environmental stimuli.

Calcium & bone metabolism
Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults: Sunghwan Ji, Kyunggon Kim, So Jeong Park, Jin Young Lee, Hee-Won Jung, Hyun Ju Yoo, Il-Young Jang, Eunju Lee, Ji Yeon Baek, Beom-Jun Kim; Endocrinol Metab. 2023;38(6):701-708. Published online October 18, 2023; DOI: https://doi.org/10.3803/EnM.2023.1783

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Abstract PDF Supplementary Material PubReader ePub: Background
Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults.
Methods
This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay.
Results
After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012).
Conclusion
These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF- 1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.

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