Endocrinology and Metabolism

Volume 38(4); August 2023

Review Articles

Diabetes, obesity and metabolism
Intrarenal Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors on Tubuloglomerular Feedback and Natriuresis: Eun Sil Koh, Gheun-Ho Kim, Sungjin Chung; Endocrinol Metab. 2023;38(4):359-372. Published online July 24, 2023; DOI: https://doi.org/10.3803/EnM.2023.1764

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When sodium-glucose cotransporter-2 (SGLT2) inhibitors were first introduced a decade ago, no one expected them to have substantial effects beyond their known glucose-lowering effects, until the emergence of evidence of their robust renal and cardiovascular benefits showing that they could attenuate progression of kidney disease, irrespective of diabetes, as well as prevent the development of acute kidney injury. Still, the precise and elaborate mechanisms underlying the major organ protection of SGLT2 inhibitors remain unclear. SGLT2 inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubule of the kidney and then recovers tubuloglomerular feedback, whereby SGLT2 inhibitors reduce glomerular hyperfiltration. This simple demonstration of their beneficial effects has perplexed experts in seeking more plausible and as yet undisclosed explanations for the whole effects of SGLT2 inhibitors, including metabolism reprogramming and the modulation of hypoxia, inflammation, and oxidative stress. Given that the renal benefits of SGLT2 inhibitors in patients with kidney disease but without diabetes were comparable to those seen in patients with diabetes, it may be reasonable to keep the emphasis on their hemodynamic actions. In this context, the aim of the present review is to provide a comprehensive overview of renal hemodynamics in individuals with diabetes who are treated with SGLT2 inhibitors, with a focus on natriuresis associated with the regulation of tubuloglomerular feedback and potential aquaresis. Throughout the discussion of alterations in renal sodium and water transports, particular attention will be given to the potential enhancement of adenosine and its receptors following SGLT2 inhibition.

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Results from a cross-specialty consensus on optimal management of patients with chronic kidney disease (CKD): from screening to complications
Mustafa Arici, Samir Helmy Assaad-Khalil, Marcello Casaccia Bertoluci, Jason Choo, Yau-Jiunn Lee, Magdalena Madero, Guillermo Javier Rosa Diez, Vicente Sánchez Polo, Sungjin Chung, Teerawat Thanachayanont, Carol Pollock
BMJ Open.2024; 14(3): e080891. CrossRef
Chronic Kidney Disease and SGLT2 Inhibitors
Eun Sil Koh, Sungjin Chung
The Journal of Korean Diabetes.2024; 25(1): 16. CrossRef
Genitourinary Tract Infections in Patients Taking SGLT2 Inhibitors
Veraprapas Kittipibul, Zachary L. Cox, Supavit Chesdachai, Mona Fiuzat, JoAnn Lindenfeld, Robert J. Mentz
Journal of the American College of Cardiology.2024; 83(16): 1568. CrossRef
Effects of Sodium–Glucose Co-Transporter 2 Inhibitors on Serum Chloride Concentrations in Patients with Heart Failure
Ivana Jurin, Vanja Ivanović Mihajlović, Zrinka Šakić, Marin Pavlov, Tomislav Šipić, Petra Vitlov, Hrvoje Falak, Danijela Grizelj, Šime Manola, Mario Udovičić
Journal of Cardiovascular Development and Disease.2024; 11(11): 364. CrossRef
Synopsis of the Korean Society of Nephrology 2023 Practical Recommendations for the Management of Diabetic Kidney Disease
Sungjin Chung
The Korean Journal of Medicine.2023; 98(6): 270. CrossRef

Adrenal Gland
Recent Updates on the Management of Adrenal Incidentalomas: Seung Shin Park, Jung Hee Kim; Endocrinol Metab. 2023;38(4):373-380. Published online August 16, 2023; DOI: https://doi.org/10.3803/EnM.2023.1779

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Adrenal incidentalomas represent an increasingly common clinical conundrum with significant implications for patients. The revised 2023 European Society of Endocrinology (ESE) guideline incorporates cutting-edge evidence for managing adrenal incidentalomas. This paper provides a concise review of the updated contents of the revised guideline. In the 2023 guideline, in patients without signs and symptoms of overt Cushing’s syndrome, a post-dexamethasone cortisol level above 50 nmol/L (>1.8 μg/dL) should be considered as mild autonomous cortisol secretion. Regarding the criteria of benign adrenal adenomas, a homogeneous adrenal mass with ≤10 Hounsfield units on non-contrast computed tomography requires no further follow-up, irrespective of its size. The updated guideline also discusses steroid metabolomics using tandem mass spectrometry to discriminate malignancy. It underscores the importance of high-volume surgeons performing adrenalectomy and emphasizes the pivotal role of a multidisciplinary team approach in deciding the treatment plan for indeterminate adrenal masses. The guideline advocates for more proactive surgical treatment for indeterminate adrenal masses in young patients (<40 years) and pregnant women. This review of the 2023 ESE guideline underscores the ongoing evolution of the adrenal incidentaloma management landscape, emphasizing the need for further research and adaptation of diagnostic and therapeutic strategies.

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Personalized Management of Malignant and Non-Malignant Ectopic Mediastinal Thyroid: A Proposed 10-Item Algorithm Approach
Mara Carsote, Mihai-Lucian Ciobica, Oana-Claudia Sima, Adrian Ciuche, Ovidiu Popa-Velea, Mihaela Stanciu, Florina Ligia Popa, Claudiu Nistor
Cancers.2024; 16(10): 1868. CrossRef
Temporal trends in clinical features of patients with primary aldosteronism over 20 years
Seung Shin Park, Chang Ho Ahn, Sang Wan Kim, Jung-Min Koh, Seung Hun Lee, Jung Hee Kim
Hypertension Research.2024; 47(8): 2019. CrossRef
Steroid Profiling in the Differential Diagnosis of Cushing's Syndrome and Diagnosis of MACS
A. Nankova, T. Kamenova, V. Vasilev, At. Elenkova, D. Svinarov, G. Kirilov, S. Zaharieva
Acta Medica Bulgarica.2024; 51(2): 1. CrossRef
Adrenal incidentalomas
Ivana Ságová
Vnitřní lékařství.2024; 70(5): E9. CrossRef
Ectopic Mediastinal Thyroid: A Crossroad Between a Multi-Layered Endocrine Perspective and a Contemporary Approach in Thoracic Surgery
Claudiu Nistor, Mihai-Lucian Ciobica, Oana-Claudia Sima, Anca-Pati Cucu, Florina Vasilescu, Lucian-George Eftimie, Dana Terzea, Mihai Costachescu, Adrian Ciuche, Mara Carsote
Life.2024; 14(11): 1374. CrossRef

Thyroid
Management of Subclinical Hypothyroidism: A Focus on Proven Health Effects in the 2023 Korean Thyroid Association Guidelines: Eu Jeong Ku, Won Sang Yoo, Hyun Kyung Chung; Endocrinol Metab. 2023;38(4):381-391. Published online August 8, 2023; DOI: https://doi.org/10.3803/EnM.2023.1778

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Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) and normal free thyroxine levels. The Korean Thyroid Association recently issued a guideline for managing SCH, which emphasizes Korean-specific TSH diagnostic criteria and highlights the health benefits of levothyroxine (LT4) treatment. A serum TSH level of 6.8 mIU/L is presented as the reference value for diagnosing SCH. SCH can be classified as mild (TSH 6.8 to 10.0 mIU/L) or severe (TSH >10.0 mIU/L), and patients can be categorized as adults (age <70 years) or elderly (age ≥70 years), depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, including a thyroid peroxidase antibody test, preferably 2 to 3 months after the initial assessment. While LT4 treatment is not generally recommended for mild SCH in adults, it is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and it may be considered for those with concurrent dyslipidemia. Conversely, LT4 treatment is generally not recommended for elderly patients, regardless of SCH severity. For those SCH patients who are prescribed LT4 treatment, the dosage should be personalized, and serum TSH levels should be regularly monitored to maintain the optimal LT4 regimen.

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Clinical Implications of Different Thyroid-Stimulating Hormone (TSH) Reference Intervals between TSH Kits for the Management of Subclinical Hypothyroidism
Won Sang Yoo
Endocrinology and Metabolism.2024; 39(1): 188. CrossRef
Serum Vitamin B12 and Holotranscobalamin Levels in Subclinical Hypothyroid Patients in Relation to Thyroid-Stimulating Hormone (TSH) Levels and the Positivity of Anti-thyroid Peroxidase Antibodies: A Case-Control Study
Muqdad Al-Mousawi, Sherwan Salih, Ameer Ahmed, Barhav Abdullah
Cureus.2024;[Epub] CrossRef

Editorial

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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Original Articles

Diabetes, obesity and metabolism
Phloretin Ameliorates Succinate-Induced Liver Fibrosis by Regulating Hepatic Stellate Cells: Cong Thuc Le, Giang Nguyen, So Young Park, Hanh Nguyen Dong, Yun Kyung Cho, Jae-Ho Lee, Seung-Soon Im, Dae-Hee Choi, Eun-Hee Cho; Endocrinol Metab. 2023;38(4):395-405. Published online August 3, 2023; DOI: https://doi.org/10.3803/EnM.2023.1661

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Background
Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study.
Methods
In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver.
Results
Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the activation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis.
Conclusion
Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.

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The potential of flavonoids in hepatic fibrosis: A comprehensive review
Zhu Wenbo, Han Jianwei, Liu Hua, Tang Lei, Chen Guijuan, Tian Mengfei
Phytomedicine.2024; 133: 155932. CrossRef
Advancements in Plant-Based Therapeutics for Hepatic Fibrosis: Molecular Mechanisms and Nanoparticulate Drug Delivery Systems
Alina Ciceu, Ferenc Fenyvesi, Anca Hermenean, Simona Ardelean, Simona Dumitra, Monica Puticiu
International Journal of Molecular Sciences.2024; 25(17): 9346. CrossRef

Diabetes, obesity and metabolism
Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study: Joon Ho Moon, Yongkang Kim, Tae Jung Oh, Jae Hoon Moon, Soo Heon Kwak, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi, Nam H. Cho; Endocrinol Metab. 2023;38(4):406-417. Published online August 3, 2023; DOI: https://doi.org/10.3803/EnM.2023.1703

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Background
While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort.
Methods
Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD.
Results
Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs.
Conclusion
The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

Citations

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Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus
Kaisheng Yuan, Bing Wu, Ruiqi Zeng, Fuqing Zhou, Ruixiang Hu, Cunchuan Wang
Diabetes, Obesity and Metabolism.2024; 26(1): 169. CrossRef
Association between the triglyceride glucose index and chronic total coronary occlusion: A cross-sectional study from southwest China
Kaiyong Xiao, Huili Cao, Bin Yang, Zhe Xv, Lian Xiao, Jianping Wang, Shuiqing Ni, Hui Feng, Zhongwei He, Lei Xv, Juan Li, Dongmei Xv
Nutrition, Metabolism and Cardiovascular Diseases.2024; 34(4): 850. CrossRef
The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999–2018
Younan Yao, Bo Wang, Tian Geng, Jiyan Chen, Wan Chen, Liwen Li
Cardiovascular Diabetology.2024;[Epub] CrossRef
Comparison of triglyceride glucose index and modified triglyceride glucose indices in prediction of cardiovascular diseases in middle aged and older Chinese adults
Cancan Cui, Yitian Qi, Jiayin Song, Xinyun Shang, Tianjiao Han, Ning Han, Siqi Yue, Yining Zha, Zhonghang Xu, Jiannan Li, Lin Liu
Cardiovascular Diabetology.2024;[Epub] CrossRef
Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers
Min Jin Lee, Ji Hyun Bae, Ah Reum Khang, Dongwon Yi, Mi Sook Yun, Yang Ho Kang
Diabetes Research and Clinical Practice.2024; 210: 111640. CrossRef
Prognostic value of triglyceride-glucose index for left ventricular remodeling in nondiabetic ST-elevation myocardial infarction patients
Tolga Han Efe, Engin Algül
Biomarkers in Medicine.2024; 18(6): 243. CrossRef
Triglyceride-Glucose Index as Predictor for Hypertension, CHD and STROKE Risk among Non-Diabetic Patients: A NHANES Cross-Sectional Study 2001–2020
Bisher Sawaf, Sarya Swed, Hidar Alibrahim, Haidara Bohsas, Tirth Dave, Mohamad Nour Nasif, Wael Hafez, Fatema Ali Asgar Tashrifwala, Yazan Khair Eldien Jabban, Safwan Al-Rassas, Heba haj Saleh, Abdul Rehman Zia Zaidi, Baraa Alghalyini, Shaymaa Abdelmaboud
Journal of Epidemiology and Global Health.2024; 14(3): 1152. CrossRef
An Increasing Triglyceride–Glucose Index Is Associated with a Pro-Inflammatory and Pro-Oxidant Phenotype
Beverley Adams-Huet, Ishwarlal Jialal
Journal of Clinical Medicine.2024; 13(13): 3941. CrossRef
Elevated triglyceride-glucose index as a predictor of carotid plaque incidence: Insights from a comprehensive meta-analysis
Arankesh Mahadevan, Bhavin A. Patel, Sashwath Srikanth, Raja Godasi, Rupak Desai
The American Journal of the Medical Sciences.2024;[Epub] CrossRef
Inflammatory and Metabolic Predictors of Mortality in Pulmonary Thromboembolism: A Focus on the Triglyceride–Glucose Index and Pan-Immune Inflammation Value
Murat Bilgin, Emre Akkaya, Recep Dokuyucu
Journal of Clinical Medicine.2024; 13(19): 6008. CrossRef
Evaluation of the novel three lipid indices for predicting five- and ten-year incidence of cardiovascular disease: findings from Kerman coronary artery disease risk factors study (KERCADRS)
Alireza Jafari, Hamid Najafipour, Mitra Shadkam, Sina Aminizadeh
Lipids in Health and Disease.2023;[Epub] CrossRef

Diabetes, obesity and metabolism
Greater Severity of Steatosis Is Associated with a Higher Risk of Incident Diabetes: A Retrospective Longitudinal Study: Ji Min Han, Jung Hwan Cho, Hye In Kim, Sunghwan Suh, Yu-Ji Lee, Jung Won Lee, Kwang Min Kim, Ji Cheol Bae; Endocrinol Metab. 2023;38(4):418-425. Published online July 12, 2023; DOI: https://doi.org/10.3803/EnM.2023.1729

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Abstract PDF PubReader ePub: Background
Fatty liver is associated with increased risk of developing type 2 diabetes. We aimed to evaluate whether the severity of hepatic steatosis is associated with incident diabetes.
Methods
We conducted a longitudinal analysis using data from 1,798 participants who underwent a comprehensive health checkup and abdominal computed tomography (CT). We assessed the association between baseline liver attenuation value on non-contrast CT images and risk of incident diabetes. All the participants were categorized into three groups based on the baseline liver attenuation value on non-contrast CT images: without hepatic steatosis (>57 Hounsfield unit [HU]), mild hepatic steatosis (41–57 HU), and moderate to severe hepatic steatosis (≤40 HU).
Results
During a median follow-up period of 5 years, 6.0% of the study participants progressed to diabetes. The incidence of diabetes was 17.3% in the moderate to severe hepatic steatosis group, 9.0% in the mild steatosis group, and 2.9% in those without hepatic steatosis. In a multivariate adjustment model, as compared with participants without hepatic steatosis, those with moderate to severe steatosis had a hazard ratio (HR) of 3.24 (95% confidence interval [CI], 1.64 to 4.2) for the development of diabetes, and those in the mild steatosis group had a HR of 2.33 (95% CI, 1.42 to 3.80). One standard deviation decrease in mean CT attenuation values of the liver was associated with a 40% increase in the development of diabetes (multivariate adjusted HR, 1.40; 95% CI, 1.2 to 1.63).
Conclusion
We found a positive association between severity of hepatic steatosis and risk of incident diabetes. Greater severity of steatosis was associated with a higher risk of incident diabetes.

Diabetes, obesity and metabolism
Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis: Mee Kyoung Kim, Kyungdo Han, Hyuk-Sang Kwon, Soon Jib Yoo; Endocrinol Metab. 2023;38(4):426-435. Published online July 20, 2023; DOI: https://doi.org/10.3803/EnM.2023.1737

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Background
The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results.
Methods
This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis.
Results
During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure.
Conclusion
In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.

Citations

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Diabetes Duration, Cholesterol Levels, and Risk of Cardiovascular Diseases in Individuals With Type 2 Diabetes
Mee Kyoung Kim, Kyu Na Lee, Kyungdo Han, Seung-Hwan Lee
The Journal of Clinical Endocrinology & Metabolism.2024; 109(12): e2317. CrossRef
Anti-Diabetic Therapies and Cancer: From Bench to Bedside
Dimitris Kounatidis, Natalia G. Vallianou, Irene Karampela, Eleni Rebelos, Marina Kouveletsou, Vasileios Dalopoulos, Petros Koufopoulos, Evanthia Diakoumopoulou, Nikolaos Tentolouris, Maria Dalamaga
Biomolecules.2024; 14(11): 1479. CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study: Hwa Young Ahn, Sun Wook Cho, Mi Young Lee, Young Joo Park, Bon Seok Koo, Hang-Seok Chang, Ka Hee Yi; Endocrinol Metab. 2023;38(4):436-444. Published online July 12, 2023; DOI: https://doi.org/10.3803/EnM.2023.1684

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Background
This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service.
Methods
This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months.
Results
The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients.
Conclusion
In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

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Long-term Effect of Thyrotropin-binding Inhibitor Immunoglobulin on Atrial Fibrillation in Euthyroid Patients
Jung-Chi Hsu, Kang-Chih Fan, Ting-Chuan Wang, Shu-Lin Chuang, Ying-Ting Chao, Ting-Tse Lin, Kuan-Chih Huang, Lian-Yu Lin, Lung-Chun Lin
Endocrine Practice.2024; 30(6): 537. CrossRef
Treatment Patterns and Preferences for Graves’ Disease in Korea: Insights from a Nationwide Cohort Study
Kyeong Jin Kim, Jimi Choi, Soo Myoung Shin, Jung A Kim, Kyoung Jin Kim, Sin Gon Kim
Endocrinology and Metabolism.2024; 39(4): 659. CrossRef
Dynamic Risk Model for the Medical Treatment of Graves’ Hyperthyroidism according to Treatment Duration
Meihua Jin, Chae A Kim, Min Ji Jeon, Won Bae Kim, Tae Yong Kim, Won Gu Kim
Endocrinology and Metabolism.2024; 39(4): 579. CrossRef
The Current Status of Hyperthyroidism in Korea
Hyemi Kwon
Endocrinology and Metabolism.2023; 38(4): 392. CrossRef
Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case–Control Study from Korea
Hyeree Park, Sun Wook Cho, Sung Ho Lee, Kangmin Kim, Hyun-Seung Kang, Jeong Eun Kim, Aesun Shin, Won-Sang Cho
Thyroid®.2023; 33(12): 1483. CrossRef

Thyroid
Different Molecular Phenotypes of Progression in BRAF- and RAS-Like Papillary Thyroid Carcinoma: Jinsun Lim, Han Sai Lee, Jiyun Park, Kyung-Soo Kim, Soo-Kyung Kim, Yong-Wook Cho, Young Shin Song; Endocrinol Metab. 2023;38(4):445-454. Published online July 18, 2023; DOI: https://doi.org/10.3803/EnM.2023.1702

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Background
Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs.
Methods
We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment.
Results
Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status.
Conclusion
The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.

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Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways
Dumitru Andrei Iacobas, Sanda Iacobas
Genes.2024; 15(5): 621. CrossRef
A computational approach to assessing the prognostic implications of BRAF and RAS mutations in patients with papillary thyroid carcinoma
Tahereh Haghzad, Babak Khorsand, S. Adeleh Razavi, Mehdi Hedayati
Endocrine.2024; 86(2): 707. CrossRef
Correlation between gene mutations and clinical characteristics in papillary thyroid cancer: a retrospective analysis of BRAF mutations and RET rearrangements
Daisuke Uno, Kazuhira Endo, Tomomi Yoshikawa, Nobuyuki Hirai, Eiji Kobayashi, Yosuke Nakanishi, Satoru Kondo, Tomokazu Yoshizaki
Thyroid Research.2024;[Epub] CrossRef
Multi-objective genetic algorithm for multi-view feature selection
Vandad Imani, Carlos Sevilla-Salcedo, Elaheh Moradi, Vittorio Fortino, Jussi Tohka
Applied Soft Computing.2024; 167: 112332. CrossRef
Emerging Strategies for the Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer: Combining Immune Checkpoint Inhibitors with VEGF Inhibitors
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Clinical Thyroidology®.2024; 36(10): 377. CrossRef

Thyroid
Beyond Acute COVID-19: Investigating the Incidence of Subacute Thyroiditis in Long COVID-19 in Korea: Jeongmin Lee, Gi Hyeon Seo, Keeho Song; Endocrinol Metab. 2023;38(4):455-461. Published online August 8, 2023; DOI: https://doi.org/10.3803/EnM.2023.1711

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Background
The correlation between acute coronavirus disease 2019 (COVID-19) and subacute thyroiditis (SAT) has not been clearly investigated in “long COVID” patients. We aimed to investigate the incidence of SAT during convalescence and after the acute phase of COVID-19, comparing with that of the general population.
Methods
Data from a total of 422,779 COVID-19 patients and a control group of 2,113,895 individuals were analyzed. The index date was defined as the date 3 months after confirmation of COVID-19. The incidence rate (IR) of SAT and hazard ratios (HRs) were calculated per 100,000 persons. Subgroup analysis included analysis of HRs 90–179 and 180 days post-COVID-19 diagnosis; and additional analysis was conducted according to hospitalization status, sex, and age group.
Results
The IR of SAT was 17.28 per 100,000 persons (95% confidence interval [CI], 12.56 to 23.20) in the COVID-19 group and 8.63 (95% CI, 6.37 to 11.45) in the control group. The HR of COVID-19 patients was 1.76 (95% CI, 1.01 to 3.06; P=0.045). The HR of SAT was 1.39 (95% CI, 0.82 to 2.34; P=0.220) up to 6 months after the index date and 2.30 (95% CI, 1.60 to 3.30; P<0.001) beyond 6 months. The HR for SAT among COVID-19 patients was 2.00 (95% CI, 1.41 to 2.83) in hospitalized patients and 1.76 (95% CI, 1.01 to 3.06) in non-hospitalized patients compared to the control group. The IR of SAT was 27.09 (95% CI, 20.04 to 35.82) for females and 6.47 (95% CI, 3.34 to 11.30) for males. In the 19 to 64 age group, the IR of SAT was 18.19 (95% CI, 13.70 to 23.67), while the IR was 9.18 (95% CI, 7.72 to 10.84) in the 65 to 69 age group.
Conclusion
SAT could be a potential long-term complication of COVID-19. Long-term surveillance for thyroid dysfunction is needed especially in hospitalized, female and young-aged subjects.

Citations

Citations to this article as recorded by

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