Background Patients with thyroid cancer receive thyroid-stimulating hormone suppressive therapy and radioactive iodine therapy, which can alter metabolism and affect the association between lifestyle factors and cardiovascular disease (CVD) outcomes. However, it remains unclear how changes in lifestyle relate to CVD risk, particularly according to metastatic status. We investigated the impact of baseline and changing lifestyle behaviors on CVD risk among thyroid cancer patients by metastasis status.
Methods This study was a nationwide cohort study using data from the Korean National Health Insurance Service claims database with the Cancer Clinical Library Database from the Korea Clinical Data Utilization Network for Research Excellence project. Over a mean follow-up of 5.7 years, 99,742 thyroid cancer patients were analyzed.
Results Current smoking increased CVD risk in both no metastasis (NM) group (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.33 to 2.35) and the local metastasis (LM) group (HR, 1.30; 95% CI, 1.00 to 1.68), but not in those with distant metastasis. Regular activity reduced the risk in the NM group (HR, 0.84; 95% CI, 0.79 to 0.96). Alcohol consumption was not significantly associated with the CVD risk. Sustained smoking showed an increased CVD risk in both NM (HR, 1.95; 95% CI, 1.31 to 2.90) and LM (HR, 1.88; 95% CI, 1.28 to 2.77). Sustained regular physical activity was associated with a lower risk of CVD only in NM (HR, 0.68; 95% CI, 0.53 to 0.87).
Conclusion Sustained smoking increased CVD risk, while regular physical activity was associated with a lower risk of CVD, particularly in those without distant metastasis.
Jeongmin Lee, Hidenori Fukuoka, Seung Shin Park, A Ram Hong, Jung Hee Kim, Sang Ouk Chin, Han-Sang Baek, Dong-Jun Lim, Kazunori Kageyama, Mitsuru Nishiyama, Shigeyuki Tahara, Kenichi Oyama, Akira Sugawara, Miho Yamashita, Naoko Inoshita, Hiroshi Arima, Byung-Joon Kim, Yoon-Sok Chung, Soon Jib Yoo, Michio Otsuki, Mi-kyung Kim, The Committee of Clinical Practice Guideline of Korean Endocrine Society, Korean Neuroendocrine Study Group of Korean Endocrine Society
Endocrinol Metab. 2026;41(1):1-13. Published online January 1, 2026
Cushing’s disease (CD) is a rare but serious endocrine disorder caused by excessive cortisol secretion due to adrenocorticotropic hormone–secreting pituitary tumors. Despite recent developments in diagnostic criteria and treatment options, CD remains associated with substantial comorbidities and mortality. Early and accurate diagnosis is thus essential. Both the Korean Endocrine Society (KES) and Japan Endocrine Society (JES) guidelines are intended to standardize diagnostic approaches to CD, and they share common principles; however, notable differences exist, particularly in biochemical testing thresholds and imaging recommendations. This consensus statement integrates clinical evidence and expert practice from both the KES and JES to establish harmonized recommendations for biochemical evaluation, imaging, and differential testing. This unified framework is intended to enhance diagnostic precision and improve clinical outcomes across East Asian populations.
Original Article
Mineral, bone & muscle Big Data Articles (National Health Insurance Service Database)
Background Despite the critical role of vitamin D in various biological processes, its impact on frailty—a condition closely linked to biological age—remains inconclusive. This study aimed to explore the association between serum 25-hydroxyvitamin D (25[OH] D) levels and frailty status in older Korean adults, utilizing a comprehensive frailty index (FI) and a nationally representative dataset.
Methods This cross-sectional study included 6,589 participants aged ≥65 years from the Korea National Health and Nutrition Examination Survey (2008–2012). Frailty was assessed using a deficit accumulation FI based on 38 physical, cognitive, psychological, and social items.
Results After adjusting for potential confounders, frail men showed 6.8% lower serum 25(OH)D concentrations compared to nonfrail controls (P=0.007). Men in the lowest serum 25(OH)D quartile (≤39.3 nmol/L) exhibited a 5.3% higher FI (P=0.047) and 1.71-fold increased odds of frailty (P=0.005), compared to those in the highest quartile (>63.3 nmol/L). Similarly, men with vitamin D deficiency (<30 nmol/L) exhibited a 9.6% higher FI compared to those with sufficient vitamin D levels (≥50 nmol/L; P=0.004). However, no significant association between serum 25(OH)D concentration and frailty was observed in women across any analysis.
Conclusion These findings suggest that low serum 25(OH)D concentrations are a potential risk factor for frailty, particularly in men. Further research is warranted to determine whether vitamin D supplementation in such high-risk older adults could help mitigate frailty.
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Shinje Moon, Young Shin Song, Kyong Yeun Jung, Eun Kyung Lee, Jeongmin Lee, Dong-Jun Lim, Chan Kwon Jung, Young Joo Park, on Behalf of the Korean Thyroid Association Clinical Guideline Committee
Endocrinol Metab. 2025;40(3):357-384. Published online June 24, 2025
In 2024, the Korean Thyroid Association (KTA) introduced a revised Risk Stratification System (K-RSS) for differentiated thyroid cancer, building upon the modified RSS (M-RSS) proposed by the American Thyroid Association in 2015. The K-RSS emphasizes the cumulative impact of coexisting clinical and pathological features, acknowledging that multiple intermediate-risk factors collectively indicate a higher recurrence risk. Histologic classification follows the 2022 World Health Organization classification, consolidating encapsulated follicular-patterned thyroid carcinomas, including invasive encapsulated follicular variant papillary thyroid carcinoma, follicular thyroid carcinoma, and oncocytic carcinoma of the thyroid gland, and stratifying them by the extent of capsular and vascular invasion. High-grade thyroid carcinoma is newly included. Updated criteria for tumor size and extrathyroidal extension (ETE) represent another significant change. BRAFV600E-mutated papillary thyroid carcinomas measuring 1 to 2 cm are now considered lower risk than previously classified in the M-RSS, while encapsulated follicular-patterned tumors larger than 4 cm are considered higher risk. Both minimal ETE and gross ETE confined to the strap muscles have been downgraded to low and intermediate risk, respectively. These changes are accompanied by updates regarding molecular profiling and surgical margin status. Collectively, these updates aim to minimize overtreatment in low-risk patients, while ensuring intensified management for those at higher risk.
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Endocrinol Metab. 2025;40(3):307-341. Published online June 24, 2025
The increasing detection of papillary thyroid microcarcinoma (PTMC) has raised concerns regarding overtreatment. For low-risk PTMC, either immediate surgery or active surveillance (AS) can be considered. To facilitate the implementation of AS, the Korean Thyroid Association convened a multidisciplinary panel and developed the first Korean guideline. AS is recommended for adults with pathologically confirmed Bethesda V–VI PTMC who have no clinical evidence of lymph node or distant metastasis, gross extrathyroidal extension, invasion of the trachea or recurrent laryngeal nerve, or aggressive histology. A baseline assessment requires high-resolution neck ultrasound performed by experienced operators to exclude extrathyroidal extension, tracheal or recurrent laryngeal nerve invasion, and lymph node metastasis; contrast-enhanced neck computed tomography is optional. Patient characteristics, including age, comorbidities, and the capacity for long-term follow-up, should be thoroughly assessed. Shared decision-making should carefully weigh the benefits and risks of surgery versus AS, considering expected oncologic outcomes, potential complications, quality of life, anxiety, medical costs, and patient preference. Follow-up involves neck ultrasound and thyroid function tests every 6 months for 2 years and annually thereafter. Disease progression, defined as significant tumor growth or newly detected nodal or distant metastasis, warrants surgery. Despite remaining uncertainties, this guideline provides a structured framework to ensure oncologic safety and supports patient-centered AS.
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Original Articles
Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Background This study investigated the association between the triglyceride-glucose (TyG) index, a marker of insulin resistance, and the risk of end-stage renal disease (ESRD) in individuals with type 2 diabetes mellitus (T2DM), focusing on variations by diabetes duration.
Methods We analyzed 1,219,148 Korean adults with T2DM from National Health Insurance Service data who underwent biennial health evaluations (2015 to 2016). ESRD was defined using specific procedural codes (V codes), and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for ESRD across TyG index quartiles and diabetes duration categories, adjusting for various confounders.
Results Over 6,967,381 person-years of follow-up, 7,548 participants developed ESRD. Higher TyG index quartiles were independently associated with increased risk of ESRD, which was more pronounced with longer diabetes duration. The adjusted HR for ESRD in the highest TyG quartile (Q4) compared to the lowest quartile (Q1) was 1.235 (95% confidence interval [CI], 0.995 to 1.533) in new-onset diabetes, and 1.592 (95% CI, 1.465 to 1.730) in those with diabetes for ≥10 years. Compared to the lowest TyG quartile in new-onset diabetes, the adjusted HR for ESRD in the highest quartile with diabetes duration ≥10 years increased to 10.239 (95% CI, 8.440 to 12.422). Subgroup analysis revealed that a higher TyG index consistently increased the risk of ESRD, with stronger associations observed in younger individuals and those without comorbidities.
Conclusion The TyG index is a significant predictor of ESRD in T2DM, particularly in those with prolonged diabetes duration. Targeting insulin resistance early may mitigate the risk of ESRD in this population.
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Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Background We aimed to assess the association between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) risk and mortality in a large cohort of diabetes patients.
Methods A retrospective cohort study of 1,090,485 participants from the Korean National Health Insurance Service database was conducted. Participants were stratified into TyG quartiles.
Results Higher TyG index quartiles were significantly associated with an increased CVD risk and mortality risk. In fully adjusted models, participants in the highest TyG quartile (Q4) had an 18% higher risk of CVD (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.13 to 1.23) and a 16% higher risk of mortality (HR, 1.16; 95% CI, 1.11 to 1.23) compared to those in the lowest quartile (Q1). The association was particularly pronounced in patients with fasting glucose ≥126 mg/dL (CVD [HR, 1.33; 95% CI, 1.29 to 1.37], mortality [HR, 1.23; 95% CI, 1.20 to 1.26]; P for interaction <0.001). Patients with a diabetes duration of ≥10 years showed the strongest association between the TyG index and CVD risk (HR, 1.44; 95% CI, 1.38 to 1.50), while the mortality risk was particularly elevated in those with a diabetes duration of less than 5 years (HR, 1.23; 95% CI, 1.18 to 1.30). Subgroup analyses revealed stronger associations between TyG index and CVD risk in younger participants, non-obese individuals, and non-smokers.
Conclusion The TyG index is a significant predictor of CVD and mortality in diabetic patients, particularly in those with poor glycemic control or longer disease duration.
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Background This study investigated the prevalence of diabetes mellitus (DM) and impaired fasting glucose, as well as their management and comorbidities among older Korean adults.
Methods Data from 269,447 individuals aged 65 years and older from the Korean National Health Insurance Service between 2000 and 2019 were analyzed to evaluate trends in DM prevalence, healthcare utilization, mortality, and complications.
Results Among 269,447 individuals, 18.6% (n=50,159/269,447) were diagnosed with DM and 27.0% (n=72,670/269,447) had impaired fasting glucose. The DM group had the highest body mass index, waist circumference, and prevalence of current smokers (P<0.001) but not the highest hypertension prevalence. From 2010 to 2019, the prevalence of DM and impaired fasting glucose increased from 15.5% to 21.9% and from 26.0% to 30.6%, respectively. Cancer-related mortality in DM was 1.15 times higher than in those with normal glucose tolerance (P<0.001), and cardiovascular disease-related mortality was 1.32 times higher (P<0.001); all mortalities were higher in female participants. Myocardial infarction (hazard ratio [HR], 1.34; P<0.001), stroke (HR, 1.24; P<0.001), and heart failure (HR, 1.13; P<0.001) were significantly higher in those with DM.
Conclusion This is the first study to investigate the prevalence of DM and related complications in older individuals based on longterm representative data in Korea. These results highlight the necessity for targeted interventions to enhance management and outcomes in this population.
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Osteoporosis management in post-menopausal women focuses on fracture prevention, with denosumab as a key therapeutic option. Despite its proven efficacy in reducing fracture risk and increasing bone mineral density (BMD) over 10 years, its long-term impact remains uncertain. We evaluated the literature on its efficacy and safety beyond the initial decade. Clinical trials and real-world studies confirm denosumab’s sustained efficacy, especially in lumbar spine BMD, with hip BMD stabilizing. Concerns about adverse events (AEs) like hypocalcemia and osteonecrosis of the jaw necessitate vigilant monitoring. Risks of atypical femoral fractures and malignancies also require attention, despite unclear links to treatment duration. Clinical guidelines for denosumab beyond 10 years are limited, emphasizing the need for careful monitoring. In certain scenarios, such as advanced chronic kidney disease, prolonged denosumab may be required to balance AE risks with fracture prevention benefits. Denosumab shows potential for long-term efficacy in augmenting BMD; however, monitoring for AEs is crucial to guide clinical decision-making effectively.
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Background Thyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1α is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1α in TAO progression.
Methods OFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1α, adipogenic differentiation markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1α inhibition, protein expression changes after HIF-1α inhibitor treatment were evaluated under normoxia and hypoxia.
Results TAO OFs exhibited significantly higher HIF-1α expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPARγ and CEBP, as well as HIF-1α in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1α inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia.
Conclusion Hypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1α activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO.
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Background This study investigates the association between thyroid function and frailty in the old patients using representative data.
Methods The study was conducted using data from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. The study population included 2,416 participants aged 50 years and older with available thyroid function test data. Frailty assessment was performed using the Fried frailty phenotype. The prevalence of frailty was analyzed across different thyroid diseases and thyroid function parameters.
Results The significant association between thyroid dysfunction and frailty was observed in overt hyperthyroidism and subclinical hyperthyroidism. After adjusting for various factors, the association between thyroid dysfunction and frailty remained significant. On the other hand, overt hypothyroidism did not show a significant association with frailty in the adjusted analysis. For individuals with overt hyperthyroidism and subclinical hyperthyroidism, higher levels of free thyroxine (FT4) were significantly associated with an increased risk of frailty (aOR >999; 95% CI, >999 to 999). Among individuals with overt hypothyroidism, lower level of FT4 levels and high thyrotropin (TSH) levels showed a significant association with frailty risk (FT4: aOR, <0.01; TSH: aOR, 999). In participants with subclinical hypothyroidism, there were no significant associations between parameters for thyroid and frailty risk.
Conclusion These findings suggest that thyroid dysfunction, particularly overt hyperthyroidism and subclinical hyperthyroidism, may be associated with an increased risk of frailty in the old patients.
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Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung, The Committee of Clinical Practice Guideline of Korean Endocrine Society, The Korean Adrenal Study Group of Korean Endocrine Society
Endocrinol Metab. 2023;38(6):597-618. Published online October 13, 2023
Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.
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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.
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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 (AUC1yr) 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 AUC1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC1yr for TSI bioassay, P=0.0125; AUC1yr 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.
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Endocrinol Metab. 2023;38(2):260-268. Published online April 27, 2023
Background Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures.
Methods We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider’s medical specialty, the proximity to the medical center, and financial burdens of treatment.
Results Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over –2.5, and in five (2.3%) patients due to expected dental procedures.
Conclusion Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment.
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Background Patients with thyroid cancer undergo less extensive surgery and additional therapies compared to those with other cancers. We aimed to compare the quality of life (QoL) between patients with thyroid cancer and healthy subjects using representative data from Korea. Differences in QoL of thyroid cancer survivors according to the duration after cancer diagnosis was also evaluated.
Methods This population-based cohort study included 50,278 subjects who participated in the Korea National Health and Nutrition Examination Survey between 2007 and 2017. QoL was compared between patients with thyroid cancer and healthy subjects using self-reported data from the EuroQoL (EQ)-5 dimension (5D) and EQ-visual analog scale (VAS). Propensity score matching was used to match thyroid cancer survivors to healthy subjects (1:5 matching).
Results Linear regression with univariate analysis showed that the presence of thyroid cancer was positively correlated with better EQ-5D index scores (β-coefficient=0.010, p=0.046). After adjusting for multiple covariables, statistical significance was maintained. EQ-VAS fails to demonstrate any significant correlation. Among the EQ-5D categories, patients with thyroid cancer showed better self-care than healthy subjects. Thyroid cancer duration did not correlate with the EQ-5D index score. In subgroup analyses, compared to patients with thyroid cancer duration of <5 years, no significant difference was observed in the correlation between the EQ-5D index score and survival duration in those with thyroid cancer duration of 5 to 9 years and ≥10 years.
Conclusion Using a large-scale nationwide population-based database, our study demonstrated better QoL, especially in terms of self-care, among thyroid cancer survivors than among healthy subjects without cancer.
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