Endocrinology and Metabolism

Original Articles

Thyroid Thyroid Cancer Screening
Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population: Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chul-Min Kim; Endocrinol Metab. 2024;39(2):310-323. Published online April 9, 2024; DOI: https://doi.org/10.3803/EnM.2023.1870

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Abstract PDF Supplementary Material PubReader ePub: Background
There is debate about ultrasonography screening for thyroid cancer and its cost-effectiveness. This study aimed to evaluate the cost-effectiveness of early screening (ES) versus symptomatic detection (SD) for differentiated thyroid cancer (DTC) in Korea.
Methods
A Markov decision analysis model was constructed to compare the cost-effectiveness of ES and SD. The model considered direct medical costs, health outcomes, and different diagnostic and treatment pathways. Input data were derived from literature and Korean population studies. Incremental cost-effectiveness ratio (ICER) was calculated. Willingness-to-pay (WTP) threshold was set at USD 100,000 or 20,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address uncertainties of the model’s variables.
Results
In a base case scenario with 50 years of follow-up, ES was found to be cost-effective compared to SD, with an ICER of $2,852 per QALY. With WTP set at $100,000, in the case with follow-up less than 10 years, the SD was cost-effective. Sensitivity analysis showed that variables such as lobectomy probability, age, mortality, and utility scores significantly influenced the ICER. Despite variations in costs and other factors, all ICER values remained below the WTP threshold.
Conclusion
Findings of this study indicate that ES is a cost-effective strategy for DTC screening in the Korean medical system. Early detection and subsequent lobectomy contribute to the cost-effectiveness of ES, while SD at an advanced stage makes ES more cost-effective. Expected follow-up duration should be considered to determine an optimal strategy for DTC screening.

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.

Thyroid
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; Endocrinol Metab. 2023;38(3):338-346. Published online June 9, 2023; DOI: https://doi.org/10.3803/EnM.2023.1664

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Background
To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatment with an anti-thyroid drug (ATD) can predict prognosis of Graves’ disease (GD) in real-world practice.
Methods
This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline and at follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patients who experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation (remission). The slope and area under the curve at 1st year (AUC_1yr) of thyroid-stimulating hormone receptor antibodies including TSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and second values divided by time duration (year).
Results
Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in response to ATD than the remission group (–84.7 [TSI slope, –198.2 to 8.2] vs. –120.1 [TSI slope, –204.4 to –45.9], P=0.026), whereas the TBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC_1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC_1yr for TSI bioassay, P=0.0125; AUC_1yr for TBII, P=0.001).
Conclusion
Early changes in TSI bioassay can better predict prognosis of GD than TBII. Measurement of TSI bioassay at beginning and follow-up could help predict GD prognosis.

Citations

Citations to this article as recorded by

Enhanced predictive validity of integrative models for refractory hyperthyroidism considering baseline and early therapy characteristics: a prospective cohort study
Xinpan Wang, Tiantian Li, Yue Li, Qiuyi Wang, Yun Cai, Zhixiao Wang, Yun Shi, Tao Yang, Xuqin Zheng
Journal of Translational Medicine.2024;[Epub] CrossRef
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;[Epub] CrossRef

Response

Diabetes, Obesity and Metabolism
Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes (Endocrinol Metab 2022;37:641-51, Han-sang Baek et al.): Han-sang Baek, Ji-Yeon Park, Jin Yu, Joonyub Lee, Yeoree Yang, Jeonghoon Ha, Seung Hwan Lee, Jae Hyoung Cho, Dong-Jun Lim, Hun-Sung Kim; Endocrinol Metab. 2022;37(6):945-946. Published online December 2, 2022; DOI: https://doi.org/10.3803/EnM.2022.602; [Original]

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Original Articles

Diabetes, Obesity and Metabolism
Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes: Han-sang Baek, Ji-Yeon Park, Jin Yu, Joonyub Lee, Yeoree Yang, Jeonghoon Ha, Seung Hwan Lee, Jae Hyoung Cho, Dong-Jun Lim, Hun-Sung Kim; Endocrinol Metab. 2022;37(4):641-651. Published online August 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1501

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Background
The prevalence of young-onset diabetes (YOD) has been increasing worldwide. As the incidence of YOD increases, it is necessary to determine the characteristics of YOD and the factors that influence its development and associated complications.
Methods
In this retrospective study, we recruited patients who were diagnosed with type 2 diabetes mellitus between June 2001 and December 2021 at a tertiary hospital. The study population was categorized according to age: YOD (age <40 years), middle-age-onset diabetes (MOD, 40≤ age <65 years), and late-onset diabetes (LOD, age ≥65 years). We examined trends in glycemic control by analyzing fasting glucose levels during the first year in each age group. A Cox proportional-hazards model was used to determine the relative risk of developing complications according to glycemic control trends.
Results
The fasting glucose level at the time of diagnosis was highest in the YOD group (YOD 149±65 mg/dL; MOD 143±54 mg/dL; and LOD 140±55 mg/dL; p=0.009). In the YOD group, glucose levels decreased at 3 months, but increased by 12 months. YOD patients and those with poor glycemic control in the first year were at a higher risk of developing complications, whereas the risk in patients with LOD was not statistically significant.
Conclusion
YOD patients had higher glucose levels at diagnosis, and their glycemic control was poorly maintained. As poor glycemic control can influence the development of complications, especially in young patients, intensive treatment is necessary for patients with YOD.

Citations

Citations to this article as recorded by

Increased risk of incident mental disorders in adults with new-onset type 1 diabetes diagnosed after the age of 19: A nationwide cohort study
Seohyun Kim, Gyuri Kim, So Hyun Cho, Rosa Oh, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
Diabetes & Metabolism.2024; 50(1): 101505. CrossRef
Association between age at diagnosis of type 2 diabetes and cardiovascular morbidity and mortality risks: A nationwide population-based study
Da Hea Seo, Mina Kim, Young Ju Suh, Yongin Cho, Seong Hee Ahn, Seongbin Hong, So Hun Kim
Diabetes Research and Clinical Practice.2024; 208: 111098. CrossRef
Impact of diabetes distress on glycemic control and diabetic complications in type 2 diabetes mellitus
Hye-Sun Park, Yongin Cho, Da Hea Seo, Seong Hee Ahn, Seongbin Hong, Young Ju Suh, Suk Chon, Jeong-Taek Woo, Sei Hyun Baik, Kwan Woo Lee, So Hun Kim
Scientific Reports.2024;[Epub] CrossRef
Early onset type 2 diabetes mellitus: an update
Myrsini Strati, Melpomeni Moustaki, Theodora Psaltopoulou, Andromachi Vryonidou, Stavroula A. Paschou
Endocrine.2024;[Epub] CrossRef
Complications and Treatment of Early-Onset Type 2 Diabetes
Fahimeh Soheilipour, Naghmeh Abbasi Kasbi, Mahshid Imankhan, Delaram Eskandari
International Journal of Endocrinology and Metabolism.2023;[Epub] CrossRef
Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes (Endocrinol Metab 2022;37:641-51, Han-sang Baek et al.)
Han-sang Baek, Ji-Yeon Park, Jin Yu, Joonyub Lee, Yeoree Yang, Jeonghoon Ha, Seung Hwan Lee, Jae Hyoung Cho, Dong-Jun Lim, Hun-Sung Kim
Endocrinology and Metabolism.2022; 37(6): 945. CrossRef
ISPAD Clinical Practice Consensus Guidelines 2022: Management of the child, adolescent, and young adult with diabetes in limited resource settings
Anju Virmani, Stuart J. Brink, Angela Middlehurst, Fauzia Mohsin, Franco Giraudo, Archana Sarda, Sana Ajmal, Julia E. von Oettingen, Kuben Pillay, Supawadee Likitmaskul, Luis Eduardo Calliari, Maria E. Craig
Pediatric Diabetes.2022; 23(8): 1529. CrossRef
Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes (Endocrinol Metab 2022;37:641-51, Han-sang Baek et al.)
May Thu Hla Aye, Sajid Adhi Raja, Vui Heng Chong
Endocrinology and Metabolism.2022; 37(6): 943. CrossRef

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

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

Citations

Citations to this article as recorded by

Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management
Jin Wang, Ke Wan, Xin Chang, Rui-Feng Mao
World Journal of Diabetes.2024; 15(3): 348. CrossRef
The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
Endocrinology and Metabolism.2023; 38(3): 338. CrossRef
Duplex Hemodynamic Parameters of Both Superior and Inferior Thyroid Arteries in Evaluation of Thyroid Hyperfunction Disorders
Maha Assem Hussein, Alaa Abdel Hamid, Rasha M Abdel Samie, Elshaymaa Hussein, Shereen Sadik Elsawy
International Journal of General Medicine.2022; Volume 15: 7131. CrossRef
Case 5: A 41-Year-Old Woman With Palpitation
Jiwon Yang, Kabsoo Shin, Jeongmin Lee, Jeonghoon Ha, Dong-Jun Lim, Han-Sang Baek
Journal of Korean Medical Science.2022;[Epub] CrossRef
Microvascular assessment of fascio-cutaneous flaps by ultrasound: A large animal study
Guillaume Goudot, Yanis Berkane, Eloi de Clermont-Tonnerre, Claire Guinier, Irina Filz von Reiterdank, Antonia van Kampen, Korkut Uygun, Curtis L. Cetrulo, Basak E. Uygun, Anahita Dua, Alexandre G. Lellouch
Frontiers in Physiology.2022;[Epub] CrossRef

Thyroid
Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway: Jun-Qing Jin, Jeong-Sun Han, Jeonghoon Ha, Han-Sang Baek, Dong-Jun Lim; Endocrinol Metab. 2021;36(5):1095-1110. Published online October 14, 2021; DOI: https://doi.org/10.3803/EnM.2021.1155

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Background
Peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligands have been widely shown to correlate with epithelial-mesenchymal transition (EMT) and cancer progression. Lobeglitazone (LGZ) is a novel ligand of PPAR-γ; and its role in EMT and metastasis in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to investigate the role of LGZ in metastatic behavior of PTC cells.
Methods
Half maximal inhibitory concentration (IC₅₀) values of LGZ in BRAF-mutated PTC cell lines (BCPAP and K1) were determined using MTT assay. Rosiglitazone (RGZ), the PPAR-γ ligand was used as a positive control. The protein expression of PPAR-γ, cell-surface proteins (E-cadherin, N-cadherin), cytoskeletal protein (Vimentin), transcription factor (Snail), p38 mitogenactivated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 pathway, and matrix metalloproteinase (MMP)-2 expression were measured using Western blotting. Changes in E-cadherin expression were also determined using immunocytochemistry. Cell migration and invasion were analyzed using wound healing and Matrigel invasion assays.
Results
Treatment with LGZ or RGZ significantly inhibited transforming growth factor-beta1 (TGF-β1)-induced EMT-associated processes such as fibroblast-like morphological changes, EMT-related protein expression, and increased cell migration and invasion in BCPAP and K1 cells. LGZ restored TGF-β1-induced loss of E-cadherin, as observed using immunocytochemistry. Furthermore, LGZ and RGZ suppressed TGF-β1-induced MMP-2 expression and phosphorylation of p38 MAPK, but not ERK1/2. Although there was no change in PPAR-γ expression after treatment with LGZ or RGZ, the effect of downstream processes mediated by LGZ was hampered by GW9662, a PPAR-γ antagonist.
Conclusion
LGZ inhibits TGF-β1-induced EMT, migration, and invasion through the p38 MAPK signaling pathway in a PPAR-γ-dependent manner in PTC cells.

Citations

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Diabetes Mellitus and Thyroid Cancers: Risky Correlation, Underlying Mechanisms and Clinical Prevention
Rongqian Wu, Junping Zhang, Guilin Zou, Shanshan Li, Jinying Wang, Xiaoxinlei Li, Jixiong Xu
Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 809. CrossRef
Clinicopathological Evaluation of Papillary Thyroid Microcarcinoma
Ando Takahito, Kimihito Fujii, Hirona Banno, Masayuki Saito, Yukie Ito, Mirai Ido, Manami Goto, Yukako Mouri, Junko Kousaka, Tsuneo Imai, Shogo Nakano
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Pioglitazone, a peroxisome proliferator‑activated receptor γ agonist, induces cell death and inhibits the proliferation of hypoxic HepG2 cells by promoting excessive production of reactive oxygen species
Guohao Huang, Mengfan Zhang, Manzhou Wang, Wenze Xu, Xuhua Duan, Xinwei Han, Jianzhuang Ren
Oncology Letters.2024;[Epub] CrossRef
The Activation of PPARγ by (2Z,4E,6E)-2-methoxyocta-2,4,6-trienoic Acid Counteracts the Epithelial–Mesenchymal Transition Process in Skin Carcinogenesis
Enrica Flori, Sarah Mosca, Giorgia Cardinali, Stefania Briganti, Monica Ottaviani, Daniela Kovacs, Isabella Manni, Mauro Truglio, Arianna Mastrofrancesco, Marco Zaccarini, Carlo Cota, Giulia Piaggio, Mauro Picardo
Cells.2023; 12(7): 1007. CrossRef
Cumulative exposure to metabolic syndrome increases thyroid cancer risk in young adults: a population-based cohort study
Jinyoung Kim, Kyungdo Han, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon
The Korean Journal of Internal Medicine.2023; 38(4): 526. CrossRef
Drug repositioning in thyroid cancer treatment: the intriguing case of anti-diabetic drugs
Alessia Greco, Francesca Coperchini, Laura Croce, Flavia Magri, Marsida Teliti, Mario Rotondi
Frontiers in Pharmacology.2023;[Epub] CrossRef
Fish and the Thyroid: A Janus Bifrons Relationship Caused by Pollutants and the Omega-3 Polyunsaturated Fatty Acids
Salvatore Benvenga, Fausto Famà, Laura Giovanna Perdichizzi, Alessandro Antonelli, Gabriela Brenta, Francesco Vermiglio, Mariacarla Moleti
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Identifying and categorizing compounds that reduce corneal transforming growth factor beta induced protein levels: a scoping review
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