Endocrinology and Metabolism

Original Articles

Miscellaneous
Prediction of Cardiovascular Complication in Patients with Newly Diagnosed Type 2 Diabetes Using an XGBoost/GRU-ODE-Bayes-Based Machine-Learning Algorithm: Joonyub Lee, Yera Choi, Taehoon Ko, Kanghyuck Lee, Juyoung Shin, Hun-Sung Kim; Endocrinol Metab. 2024;39(1):176-185. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1739

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Abstract PDF Supplementary Material PubReader ePub: Background
Cardiovascular disease is life-threatening yet preventable for patients with type 2 diabetes mellitus (T2DM). Because each patient with T2DM has a different risk of developing cardiovascular complications, the accurate stratification of cardiovascular risk is critical. In this study, we proposed cardiovascular risk engines based on machine-learning algorithms for newly diagnosed T2DM patients in Korea.
Methods
To develop the machine-learning-based cardiovascular disease engines, we retrospectively analyzed 26,166 newly diagnosed T2DM patients who visited Seoul St. Mary’s Hospital between July 2009 and April 2019. To accurately measure diabetes-related cardiovascular events, we designed a buffer (1 year), an observation (1 year), and an outcome period (5 years). The entire dataset was split into training and testing sets in an 8:2 ratio, and this procedure was repeated 100 times. The area under the receiver operating characteristic curve (AUROC) was calculated by 10-fold cross-validation on the training dataset.
Results
The machine-learning-based risk engines (AUROC XGBoost=0.781±0.014 and AUROC gated recurrent unit [GRU]-ordinary differential equation [ODE]-Bayes=0.812±0.016) outperformed the conventional regression-based model (AUROC=0.723± 0.036).
Conclusion
GRU-ODE-Bayes-based cardiovascular risk engine is highly accurate, easily applicable, and can provide valuable information for the individualized treatment of Korean patients with newly diagnosed T2DM.

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 Big Data Articles (National Health Insurance Service Database)
Increased Risk of Hip Fracture in Patients with Acromegaly: A Nationwide Cohort Study in Korea: Jiwon Kim, Namki Hong, Jimi Choi, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Sin Gon Kim, Cheol Ryong Ku; Endocrinol Metab. 2023;38(6):690-700. Published online October 30, 2023; DOI: https://doi.org/10.3803/EnM.2023.1782

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Abstract PDF Supplementary Material PubReader ePub: Background
Acromegaly leads to various skeletal complications, and fragility fractures are emerging as a new concern in patients with acromegaly. Therefore, this study investigated the risk of fractures in Korean patients with acromegaly.
Methods
We used the Korean nationwide claims database from 2009 to 2019. A total of 931 patients with acromegaly who had never used an osteoporosis drug before and were treated with surgery alone were selected as study participants, and a 1:29 ratio of 26,999 age- and sex-matched osteoporosis drug-naïve controls without acromegaly were randomly selected from the database.
Results
The mean age was 46.2 years, and 50.0% were male. During a median follow-up of 54.1 months, there was no difference in the risks of all, vertebral, and non-vertebral fractures between the acromegaly and control groups. However, hip fracture risk was significantly higher (hazard ratio [HR], 2.73; 95% confidence interval [CI], 1.32 to 5.65), and non-hip and non-vertebral fractures risk was significantly lower (HR, 0.40; 95% CI, 0.17 to 0.98) in patients with acromegaly than in controls; these results remained robust even after adjustment for socioeconomic status and baseline comorbidities. Age, type 2 diabetes mellitus, cardio-cerebrovascular disease, fracture history, recent use of acid-suppressant medication, psychotropic medication, and opioids were risk factors for all fractures in patients with acromegaly (all P<0.05).
Conclusion
Compared with controls, patients surgically treated for acromegaly had a higher risk of hip fractures. The risk factors for fracture in patients with acromegaly were consistent with widely accepted risk factors in the general population.

Thyroid
Long-Term Changes in the Mortality Rates of Thyroid Cancer in Korea: Analysis of Korean National Data from 1985 to 2020: Yun Mi Choi, Min-Ju Kim, Jiwoo Lee, Mi Kyung Kwak, Min Ji Jeon, Tae Yong Kim, Eun-Gyoung Hong, Won Bae Kim, Won Gu Kim; Endocrinol Metab. 2023;38(5):588-595. Published online September 8, 2023; DOI: https://doi.org/10.3803/EnM.2023.1723

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Background
Thyroid cancer mortality has been largely overlooked as relatively stable given the large gap between thyroid cancer incidence and mortality. This study evaluated long-term trends in age-standardized mortality rates (ASMRs) throughout Korea and compared them with mortality data reported by the Surveillance, Epidemiology, and End Results (SEER).
Methods
Cancer-specific mortality data from 1985 to 2020 were obtained from Statistics Korea. ASMRs from thyroid cancer were calculated based on the Korean mid-year resident registration population of 2005. We assessed SEER*Explorer and downloaded the mortality data.
Results
The ASMR increased from 0.19 to 0.77/100,000 between 1985 and 2002 but decreased continuously to 0.36/100,000 in 2020. The annual percent change (APC) in the ASMR between 1985 and 2003 and between 2003 and 2020 was 6.204 and −4.218, respectively, with similar patterns observed in both men and women. The ASMR of the SEER showed a modest increase from 1988 to 2016 and then stabilized. In subgroup analysis, the ASMR of the old age group (≥55 years) increased significantly from 0.82 in 1985 to 3.92/100,000 in 2002 (APC 6.917) but then decreased again to 1.86/100,000 in 2020 (APC −4.136). ASMRs according to the age group in the SEER showed a relatively stable trend even in the elderly group.
Conclusion
The ASMR of thyroid cancer in Korea had increased from 1985 to 2002 but has since been steadily decreasing. This trend was mainly attributed to elderly people aged 55 or over. The absolute APC value of Korea was much higher than that of the SEER.

Citations

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It Is Time to Understand the Additional Benefits of Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Kyeong Jin Kim
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A Clinical Audit of Thyroid Hormonal Replacement After Total Thyroidectomy
Islam Mansy, Abdelfatah M Elsenosy, Eslam M Hassan, Mujtaba Zakria
Cureus.2023;[Epub] CrossRef

Review Article

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database: Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee; Endocrinol Metab. 2023;38(1):10-24. Published online February 9, 2023; DOI: https://doi.org/10.3803/EnM.2023.102

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The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

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The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1194. CrossRef
Weight change in patients with new‐onset type 2 diabetes mellitus and its association with remission: Comprehensive real‐world data
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Diabetes, Obesity and Metabolism.2024; 26(2): 567. CrossRef
Diabetes severity and the risk of depression: A nationwide population-based study
Yunjung Cho, Bongsung Kim, Hyuk-Sang Kwon, Kyungdo Han, Mee Kyoung Kim
Journal of Affective Disorders.2024; 351: 694. CrossRef
Information Bias Might Exaggerate Lung Cancer Risk of Patients With Rheumatoid Arthritis
Nobuyuki Horita, Kaoru Takase-Minegishi
Journal of Thoracic Oncology.2024; 19(2): 348. CrossRef
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
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Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up
Ji Young Kang, Kyungdo Han, Seung-Hwan Lee, Mee Kyoung Kim
Respiratory Research.2023;[Epub] CrossRef
Research on obesity using the National Health Information Database: recent trends
Eun-Jung Rhee
Cardiovascular Prevention and Pharmacotherapy.2023; 5(2): 35. CrossRef
Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study
Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
Journal of Clinical Medicine.2023; 12(14): 4799. CrossRef
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
Endocrinology and Metabolism.2023; 38(4): 426. CrossRef
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
Endocrinology and Metabolism.2023; 38(4): 436. 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
Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study
Joonyub Lee, Hun-Sung Kim, Kee-Ho Song, Soon Jib Yoo, Kyungdo Han, Seung-Hwan Lee
Endocrinology and Metabolism.2023; 38(5): 525. CrossRef
Risk of depression in patients with acromegaly in Korea (2006-2016): a nationwide population-based study
Shinje Moon, Sangmo Hong, Kyungdo Han, Cheol-Young Park
European Journal of Endocrinology.2023; 189(3): 363. CrossRef
Cumulative effect of impaired fasting glucose on the risk of dementia in middle-aged and elderly people: a nationwide cohort study
Jin Yu, Kyu-Na Lee, Hun-Sung Kim, Kyungdo Han, Seung-Hwan Lee
Scientific Reports.2023;[Epub] CrossRef
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
Endocrinology and Metabolism.2023; 38(6): 770. CrossRef
Increased Risk of Hip Fracture in Patients with Acromegaly: A Nationwide Cohort Study in Korea
Jiwon Kim, Namki Hong, Jimi Choi, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Sin Gon Kim, Cheol Ryong Ku
Endocrinology and Metabolism.2023; 38(6): 690. CrossRef

Original Articles

Thyroid Big Data Articles (National Health Insurance Service Database)
Recent Changes in the Incidence of Thyroid Cancer in Korea between 2005 and 2018: Analysis of Korean National Data: Yun Mi Choi, Jiwoo Lee, Mi Kyung Kwak, Min Ji Jeon, Tae Yong Kim, Eun-Gyoung Hong, Won Bae Kim, Won Gu Kim; Endocrinol Metab. 2022;37(5):791-799. Published online October 11, 2022; DOI: https://doi.org/10.3803/EnM.2022.1533

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Background
In this study, we evaluated the recent changes in the standardized, age-specific, stage-specific incidence rates (IRs) of thyroid cancer in Korea and compared them with the incidence data reported by the Surveillance, Epidemiology, and End Results Program.
Methods
The analysis was conducted using the incidence data (2005 to 2018) from the Statistics Korea and Korea Central Cancer Registry.
Results
The age-standardized IR (SIR) of thyroid cancer increased from 24.09 per 100,000 in 2005 to 74.83 in 2012 (annual percent change [APC], 14.5). From 2012 to 2015, the SIR decreased to 42.52 (APC, –17.9) and then remained stable until 2018 (APC, 2.1). This trend was similar in both men and women. Regarding age-specific IRs, the IRs for ages of 30 years and older showed a trend similar to that of the SIR; however, for ages below 30 years, no significant reduction was observed from the vertex of IR in 2015. Regarding stage-specific IRs, the increase was more prominent in those with regional disease (APC, 17.4) than in those with localized disease until 2012; then, the IR decreased until 2015 (APC, –16.1). The average APC from 2005 to 2018 increased in men, those under the age of 30 years, and those with regional disease.
Conclusion
The SIR in Korea peaked in 2012 and decreased until 2015 and then remained stable until 2018. However, in young individuals under the age of 30 years, the IR did not significantly decrease but tended to increase again. In terms of stage-specific IRs, the sharpest increase was seen among those with regional disease.

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Comparison of postoperative pain between transoral and conventional thyroidectomy: a propensity score-matched analysis
Min Kyu Park, Van Cuong Nguyen, Eugene Kim, Chang Myeon Song, Yong Bae Ji, Jin Hyeok Jeong, Kyung Tae
Surgical Endoscopy.2024; 38(3): 1512. CrossRef
Contents analysis of thyroid cancer-related information uploaded to YouTube by physicians in Korea: endorsing thyroid cancer screening, potentially leading to overdiagnosis
EunKyo Kang, HyoRim Ju, Soojeong Kim, Juyoung Choi
BMC Public Health.2024;[Epub] CrossRef
Bilateral axillo-breast approach robotic total thyroidectomy without isthmectomy: a case report
Hyeji Kim, Hyeonuk Hwang, Hyungju Kwon
The Ewha Medical Journal.2024;[Epub] CrossRef
Association between Consumption of Iodine-Rich Foods and Thyroid Cancer Prevalence: Findings from a Large Population-Based Study
Yu-Jin Kwon, Hye-Sun Lee, Sang-Wook Kang, Ji-Won Lee
Nutrients.2024; 16(7): 1041. CrossRef
Cancer and Mortality Risks of Graves’ Disease in South Korea Based on National Data from 2010 to 2019
Young Ju Choi, Kyungdo Han, Won Kyoung Cho, Min Ho Jung, Byung-Kyu Suh
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Survival Comparison of Incidentally Found versus Clinically Detected Thyroid Cancers: An Analysis of a Nationwide Cohort Study
Shinje Moon, Eun Kyung Lee, Hoonsung Choi, Sue K. Park, Young Joo Park
Endocrinology and Metabolism.2023; 38(1): 81. CrossRef
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
Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Jaseong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chulmin Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef
Long-Term Changes in the Mortality Rates of Thyroid Cancer in Korea: Analysis of Korean National Data from 1985 to 2020
Yun Mi Choi, Min-Ju Kim, Jiwoo Lee, Mi Kyung Kwak, Min Ji Jeon, Tae Yong Kim, Eun-Gyoung Hong, Won Bae Kim, Won Gu Kim
Endocrinology and Metabolism.2023; 38(5): 588. CrossRef
Age and Post-Lobectomy Recurrence after Endoscopic or Robotic Thyroid Surgery: A Retrospective Cohort Study of 2348 Papillary Thyroid Carcinoma Patients
Jin-Seong Cho, Yong-Min Na, Hee Kyung Kim
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Calcium & Bone Metabolism
Real-World Safety and Effectiveness of Denosumab in Patients with Osteoporosis: A Prospective, Observational Study in South Korea: Yumie Rhee, Dong-Gune Chang, Jeonghoon Ha, Sooa Kim, Yusun Lee, Euna Jo, Jung-Min Koh; Endocrinol Metab. 2022;37(3):497-505. Published online June 3, 2022; DOI: https://doi.org/10.3803/EnM.2022.1427

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Background
The efficacy and safety of denosumab have been established in a phase 3, randomized, placebo-controlled trial in Korean postmenopausal women with osteoporosis. This postmarketing surveillance study was aimed to investigate the safety and effectiveness of denosumab in Korean real-world clinical practice.
Methods
Patients with osteoporosis who had received denosumab per the Korean approved indications in the postmarketing setting between September 2014 and September 2019 were enrolled. The primary endpoint was the incidence of adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was the percent change from baseline in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck.
Results
Of the 3,221 patients enrolled, 3,185 were included in the safety analysis set; 2,973 (93.3%) were female, and the mean± standard deviation (SD) age was 68.9±9.9 years. The mean±SD study period was 350.0±71.4 days. AEs, fatal AEs, and ADRs occurred in 19.3%, 0.8%, and 1.6%, respectively. The most frequent AEs, occurring in >0.5% of patients, were dizziness (0.7%), arthralgia (0.7%), back pain (0.6%), and myalgia (0.6%). Hypocalcemia occurred in 0.3% of patients. There were no cases of osteonecrosis of the jaw and atypical femoral fracture. Mean±SD percent change from baseline in BMD of the lumbar spine, total hip, and femoral neck was 7.3%±23.6%, 3.6%±31.4%, and 3.2%±10.7%, respectively.
Conclusion
The safety and effectiveness of denosumab in Korean patients with osteoporosis in this study were comparable with those in the Korean randomized controlled trial, with no new safety findings.

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Anna Spångeus, Johan Rydetun, Mischa Woisetschläger
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Cost-consequence analysis of continuous denosumab therapy for osteoporosis treatment in South Korea
Seungju Cha, Minjeong Sohn, Hyowon Yang, Eric J. Yeh, Ki-Hyun Baek, Jeonghoon Ha, Hyemin Ku
BMC Musculoskeletal Disorders.2024;[Epub] CrossRef
Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis
Huei-Kai Huang, Albert Tzu-Ming Chuang, Tzu-Chi Liao, Shih-Chieh Shao, Peter Pin-Sung Liu, Yu-Kang Tu, Edward Chia-Cheng Lai
JAMA Network Open.2024; 7(2): e2354734. CrossRef
Adverse Effects of Denosumab in Kidney Transplant Recipients: A 20-Year Retrospective Single-Center Observation Study in Central Taiwan
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Transplantation Proceedings.2023; 55(4): 837. CrossRef
Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study
Chaiho Jeong, Jeongmin Lee, Jinyoung Kim, Jeonghoon Ha, Kwanhoon Jo, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Tae-Seo Sohn, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek
Endocrinology and Metabolism.2023; 38(2): 260. CrossRef
Effect of Denosumab on Bone Density in Postmenopausal Osteoporosis: A Comparison with and without Calcium Supplementation in Patients on Standard Diets in Korea
Chaiho Jeong, Jinyoung Kim, Jeongmin Lee, Yejee Lim, Dong-Jun Lim, Ki-Hyun Baek, Jeonghoon Ha
Journal of Clinical Medicine.2023; 12(21): 6904. CrossRef
Denosumab

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Denosumab, an effective osteoporosis treatment option for men
Sung Hye Kong
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Diabetes, Obesity and Metabolism
Associations of Phthalate Metabolites and Bisphenol A Levels with Obesity in Children: The Korean National Environmental Health Survey (KoNEHS) 2015 to 2017: Moon Young Seo, Shinje Moon, Shin-Hye Kim, Mi Jung Park; Endocrinol Metab. 2022;37(2):249-260. Published online April 7, 2022; DOI: https://doi.org/10.3803/EnM.2021.1235

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Background
Phthalates and bisphenol A (BPA) are synthetic chemicals widely used in daily life. This study investigated urinary phthalate and BPA levels in Korean children and their associations with obesity. Methods: A total of 2,351 children aged 3 to 17 years who participated in the Korean National Environmental Health Survey 2015 to 2017 were included. Urinary dilution was corrected using covariate-adjusted standardization (CAS). We examined the geometric mean (GM) concentrations of urinary phthalate metabolites, including di (2-ethylhexyl) phthalate (DEHP) metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate, mono [2-ethyl-5-oxohexyl] phthalate, and mono [2-ethyl-5-carboxypentyl] phthalate [MECPP]), mono-benzyl-phthalate (MBzP), mono (carboxyoctyl) phthalate (MCOP), mono (carboxy-isononyl) phthalate (MCNP), mono (3-carboxypropyl) phthalate, and mono-n-butyl-phthalate (MnBP), and BPA. We also analyzed the odds ratio (OR) for obesity according to the quartiles of each analyte. Results: The urinary GM levels of DEHP metabolites and MnBP were notably higher among Korean children than among American, Canadian, and German children. The CAS-applied GM concentrations of most analytes, except for MBzP, MCOP, and MCNP, were higher in children aged 3 to 5 years than in those aged 6 to 17 years. The OR for obesity in the highest quartile of MECPP was significantly higher than in the lowest quartile after adjusting for covariates. However, the other phthalate metabolites and BPA were not significantly associated with obesity. Conclusion: The concentrations of urinary DEHP metabolites and MnBP were higher in Korean children than in children in Western countries. Urinary MECPP exposure, but not other phthalates or BPA, showed a positive association with obesity in Korean children. Further studies are required to elucidate the causal relationships.

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Diethyl phthalate, a plasticizer, induces adipocyte inflammation and apoptosis in mice after long‐term dietary administration
Shirsha Mondal, Soumyadeep Basu, Songita Ghosh, Suktara Guria, Sutapa Mukherjee
Journal of Biochemical and Molecular Toxicology.2024;[Epub] CrossRef
Nontargeted metabolomic evidence for antagonism between tetracycline and its resistance bacteria underlying their obesogenic effects on Caenorhabditis elegans
Zhuo Li, Di Wu, Zhenyang Yu, Changzheng Cui, Daqiang Yin
Science of The Total Environment.2023; 859: 160223. CrossRef
Prospective association between phthalate exposure in childhood and liver function in adolescence: the Ewha Birth and Growth Cohort Study
Seonhwa Lee, Hye Ah Lee, Bohyun Park, Hyejin Han, Young Sun Hong, Eun Hee Ha, Hyesook Park
Environmental Health.2023;[Epub] CrossRef
Bisphenol A substitutes and childhood obesity at 7 years: a cross-sectional study in Shandong, China
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Environmental Science and Pollution Research.2023; 30(29): 73174. CrossRef
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Youming He, Jun Zou, Ting Hong, Dan Feng
Food and Chemical Toxicology.2023; 179: 113968. CrossRef
Association between phthalate exposure and obesity risk: A meta-analysis of observational studies
Qian Wu, Gang Li, Chen-Yang Zhao, Xiao-Lin Na, Yun-Bo Zhang
Environmental Toxicology and Pharmacology.2023; 102: 104240. CrossRef
Levels of Bisphenol A and its analogs in nails, saliva, and urine of children: a case control study
Yolanda Gálvez-Ontiveros, Inmaculada Moscoso-Ruiz, Vega Almazán Fernández de Bobadilla, Celia Monteagudo, Rafael Giménez-Martínez, Lourdes Rodrigo, Alberto Zafra-Gómez, Ana Rivas
Frontiers in Nutrition.2023;[Epub] CrossRef
Nontargeted Metabolomic Evidence for Antagonism between Tetracycline and its Resistance Bacteria Underlying Their Obesogenic Effects on Caenorhabditis Elegans
Zhuo Li, Zhenyang Yu, Changzheng Cui, Daqiang Yin
SSRN Electronic Journal .2022;[Epub] CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study: Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park; Endocrinol Metab. 2021;36(3):628-636. Published online May 26, 2021; DOI: https://doi.org/10.3803/EnM.2020.948

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Background
To investigate the clinical characteristics of gestational diabetes mellitus (GDM) in Korea, using a nationwide database.
Methods
We analyzed 417,139 women who gave birth between 2011 and 2015 using the Korean National Health Information Database. They underwent the Korean National Health Screening Program within one year before pregnancy and were not prescribed drugs for diabetes nor diagnosed with diabetes mellitus before 280 days antepartum. Patients with GDM were defined as those who visited the outpatient clinic more than twice with GDM codes.
Results
The prevalence of GDM was 12.70% and increased with increasing maternal age, prepregnancy body mass index (BMI), waist circumference (WC), and fasting plasma glucose (FPG) (P for trend <0.05). As compared with those aged <25 years, the odds ratio for women with GDM aged ≥40 years were 4.804 (95% confidence interval [CI], 4.436 to 5.203) after adjustment for covariates. Women with prepregnancy BMI ≥30 kg/m² were at 1.898 times (95% CI, 1.736 to 2.075) greater risk for GDM than those with prepregnancy BMI <18.5 kg/m². Women with WC of ≥95 cm were at 1.158 times (95% CI, 1.029 to 1.191) greater risk for GDM than women with WC of less than 65 cm. High FPG, high income, smoking, and drinking were associated with an elevated risk of GDM.
Conclusion
The prevalence of GDM in Korean women increased up to 12.70% during 2011 to 2015. These data suggest the importance of GDM screening and prevention in high-risk groups in Korea.

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Clinical Study
Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study: Ki-Hyun Baek, Yoon-Sok Chung, Jung-Min Koh, In Joo Kim, Kyoung Min Kim, Yong-Ki Min, Ki Deok Park, Rajani Dinavahi, Judy Maddox, Wenjing Yang, Sooa Kim, Sang Jin Lee, Hyungjin Cho, Sung-Kil Lim; Endocrinol Metab. 2021;36(1):60-69. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.848

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Background
This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis.
Methods
Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤–2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months.
Results
At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (–0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively.
Conclusion
Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

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Brief Report

Hypothalamus and Pituitary gland
Reference Ranges of Serum Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3: Results from a Multicenter Study in Healthy Korean Adults: In-Kyung Jeong, Jong Kyu Byun, Junghyun Noh, Sang Wan Kim, Yoon-Sok Chung, Tae Sun Park, Sung-Woon Kim; Endocrinol Metab. 2020;35(4):954-959. Published online December 1, 2020; DOI: https://doi.org/10.3803/EnM.2020.785

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Insulin-like growth factor-I (IGF-I) plays a pivotal role in the diagnosis and treatment of growth hormone (GH) excess or deficiency. The GH study group of the Korean Endocrine Society aims to establish the Korean reference ranges of serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) and assess the relationship between IGF-I and IGFBP-3 and clinical parameters. Fasting serum was collected from healthy Korean adults at health promotion centers of five hospitals nationwide. Serum IGF-I and IGFBP-3 were measured via an immunoradiometric assay using a DSL kit (Diagnostic Systems Laboratories). Serum samples from 354 subjects (180 male, 174 female) were analyzed based on sex at 10-year intervals from 21 to 70 years. IGF-I levels were inversely correlated with age. After adjustment of age, the IGF-I/IGFBP-3 ratio was significantly negatively associated with blood pressure and free thyroxine and positively associated with weight, hemoglobin, creatinine, alanine transferase, fasting glucose, and thyroid stimulating hormone. Therefore, age- and sex-specific reference ranges of serum IGF-I and IGFBP-3 can be efficient in evaluating GH excess or deficiency in Korean population.

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Original Article

Clinical Study
Achievement of LDL-C Targets Defined by ESC/EAS (2011) Guidelines in Risk-Stratified Korean Patients with Dyslipidemia Receiving Lipid-Modifying Treatments: Ye Seul Yang, Seo Young Lee, Jung-Sun Kim, Kyung Mook Choi, Kang Wook Lee, Sang-Chol Lee, Jung Rae Cho, Seung-Jin Oh, Ji-Hyun Kim, Sung Hee Choi; Endocrinol Metab. 2020;35(2):367-376. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.367

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Background
This study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs).
Methods
In this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed.
Results
Guideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators’ assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients’ LDL-C levels was the primary reason for non-intensification of statin therapy.
Conclusion
Achievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.

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Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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Bempedoic Acid for Lipid Management in the Indian Population: An Expert Opinion
Jagdish Hiremath, J C Mohan, Prakash Hazra, JP S Sawhney, Ashwani Mehta, Sadanand Shetty, Abraham Oomman, Mahesh K Shah, Ganapathi Bantwal, Rajeev Agarwal, Rajiv Karnik, Peeyush Jain, Saumitra Ray, Sambit Das, Vibhuti Jadhao, Sachin Suryawanshi, Hanmant B
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Julia Brandts, Sarah Bray, Guillermo Villa, Alberico L. Catapano, Neil R. Poulter, Antonio J. Vallejo-Vaz, Kausik K. Ray
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Kyung Ae Lee
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Review Articles

Hypothalamus and Pituitary gland
Epidemiology of Functioning Pituitary Adenomas: Sang Ouk Chin; Endocrinol Metab. 2020;35(2):237-242. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.237

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Pituitary adenomas (PAs) are defined as benign monoclonal tumors in the pituitary gland that cause symptoms due to either hormonal hypersecretion or a space-occupying effect, and are classified as functioning or non-functioning. Because of their rarity and slow-growing with symptomless nature in most cases, it has been challenging to investigate the epidemiology of PAs. Considering their public health impact and association with increased morbidity and mortality, however, it is essential to understand the prevalence and incidence of PAs in order to improve patient outcomes and to minimize the resultant burden on the health care system. Fortunately, developments in imaging modalities and easier access to large-scale population data have enabled investigators to analyze the epidemiology of PAs more accurately. This review summarizes previously reported epidemiologic data on functioning PAs in Korea and other countries.

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Madhala Divya, Balasubramanian Archana, Lawrence D Cruze, D. Balasubramanian
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Transcriptome of GH-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues
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Prognostic Models in Growth-Hormone- and Prolactin-Secreting Pituitary Neuroendocrine Tumors: A Systematic Review
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Luz E. Castellanos, Catherine Gutierrez, Timothy Smith, Edward R. Laws, J. Bryan Iorgulescu
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Keiko Taniguchi-Ponciano, Lesly A. Portocarrero-Ortiz, Gerardo Guinto, Sergio Moreno-Jimenez, Erick Gomez-Apo, Laura Chavez-Macias, Eduardo Peña-Martínez, Gloria Silva-Román, Sandra Vela-Patiño, Jesús Ordoñez-García, Sergio Andonegui-Elguera, Aldo Ferreir
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IL-10 Gene Rs1800871, Rs1800872, and Rs1800896 Polymorphisms and IL-10 Serum Levels Association with Pituitary Adenoma
Migle Palivonaite, Greta Gedvilaite, Brigita Glebauskiene, Loresa Kriauciuniene, Vita Rovite, Rasa Liutkeviciene
Biomedicines.2022; 10(8): 1921. CrossRef
Genome wide analysis of circulating miRNAs in growth hormone secreting pituitary neuroendocrine tumor patients’ plasma
Helvijs Niedra, Raitis Peculis, Helena Daiga Litvina, Kaspars Megnis, Ilona Mandrika, Inga Balcere, Mihails Romanovs, Liva Steina, Janis Stukens, Austra Breiksa, Jurijs Nazarovs, Jelizaveta Sokolovska, Rasa Liutkeviciene, Alvita Vilkevicute, Ilze Konrade,
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Veronica Aran, Manoela Heringer, Paulo Jose da Mata, Leandro Kasuki, Renan Lyra Miranda, Felipe Andreiuolo, Leila Chimelli, Paulo Niemeyer Filho, Monica Roberto Gadelha, Vivaldo Moura Neto
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Thyroid
Update on Thyroid Hormone Levels and Thyroid Dysfunction in the Korean Population Based on Data from the Korea National Health and Nutrition Examination Survey VI (2013 to 2015): Jae Hoon Chung; Endocrinol Metab. 2020;35(1):7-13. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.7

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In 2017, the first Korean nationwide data on serum thyroid stimulating hormone (TSH) levels, serum free thyroxine (fT₄) levels, and urinary iodine concentration (UIC) were published based on a population of 7,061 Koreans who participated in the Korea National Health and Nutrition Examination Survey VI. The mean TSH level was 2.16 mIU/L, with a reference interval of 0.59 to 7.03 mIU/L (men 2.09 mIU/L, women 2.24 mIU/L, P<0.001). A U-shaped association was found between serum TSH levels and age. The mean fT₄ level was 1.25 ng/dL, and its reference interval was 0.92 to 1.60 ng/dL (men 1.29 ng/dL, women 1.20 ng/dL, P<0.0001). Serum fT₄ levels decreased with age (P for trend <0.0001). Serum thyroid peroxidase antibody (TPOAb) was detected in 7.30% of participants (men 4.33%, women 10.62%). TPOAb titers tended to increase with age, and were higher in women than in men. The median UIC was 294 µg/L, and UIC showed a U-shaped relationship with age. According to the World Health Organization recommendations, only 23% of participants were in the adequate range of iodine intake, while 65% were in the above requirements or excessive, and 12% in insufficient. The prevalence of overt hyperthyroidism and hypothyroidism in Koreans was 0.34% to 0.54% and 0.73% to 1.43%, respectively.

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Original Article

Clinical Study
Association between Serum Gamma-Glutamyltransferase and Prevalence of Metabolic Syndrome Using Data from the Korean Genome and Epidemiology Study: Mi Young Lee, Dae Sung Hyon, Ji Hye Huh, Hae Kyung Kim, Sul Ki Han, Jang Young Kim, Sang Baek Koh; Endocrinol Metab. 2019;34(4):390-397. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.390

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Background

The aim of this study was to determine whether there is a positive correlation between gamma-glutamyltransferase (GGT) levels and the prevalence of metabolic syndrome and whether GGT can be used as an easily checkable metabolic index using data from the large-scale Korean Genome and Epidemiology Study (KoGES).

Methods

We obtained data of 211,725 participants of the KoGES. The collected data included age, sex, height, weight, waist circumference, and various biochemical characteristics, including serum GGT levels. The data of study participants who ingested more than 40 g/day of alcohol and who were diagnosed with metabolic syndrome at baseline was excluded. We analyzed the prevalence of metabolic syndrome according to GGT quartiles in both genders.

Results

The GGT level was significantly higher in subjects with metabolic syndrome compared to normal subjects (37.92±48.20 mg/dL vs. 25.62±33.56 mg/dL). The prevalence of metabolic syndrome showed a stepwise increase with GGT quartiles in both male and female subjects. Compared to the lowest GGT quartile, the odds ratio was 1.534 (95% confidence interval [CI], 1.432 to 1.643), 1.939 (95% CI, 1.811 to 2.076), and 2.754 (95% CI, 2.572 to 2.948) in men and 1.155 (95% CI, 1.094 to 1.218), 1.528 (95% CI, 1.451 to 1.609), and 2.022 (95% CI, 1.921 to 2.218) in women with increasing GGT quartile. The cutoff value of GGT predicting risk of metabolic syndrome was 27 IU/L in men and 17 IU/L in women.

Conclusion

We suggested that GGT could be an easily checkable marker for the prediction of metabolic syndrome.

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