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.
Kyeong Jin Kim, Eyun Song, Mijin Kim, Hyemi Kwon, Eu Jeong Ku, Hyun Woo Kwon, Jee Hee Yoon, Eun Kyung Lee, Won Woo Lee, Young Joo Park, Dong-Jun Lim, Sun Wook Kim, Ho-Cheol Kang, Jae Hoon Chung, Tae Yong Kim, Sin Gon Kim, Dong Gyu Na, Jee Soo Kim
Endocrinol Metab. 2025;40(3):342-356. Published online June 24, 2025
Hyperthyroidism is a condition marked by excessive thyroid hormone production, most commonly due to Graves’ disease. Treatment options include antithyroid drugs (ATD), radioactive iodine (RAI) therapy, and thyroidectomy. To develop standardized clinical recommendations for RAI therapy with a focus on safety, efficacy, and monitoring, the Korean Thyroid Association formed a task force to create evidence-based guidelines. Six key clinical questions were identified through expert consensus, and a systematic literature review from 2013 to 2022 was conducted. Clinical indications for RAI therapy were categorized into three groups: strongly recommended, may be considered, and not recommended. A fixed dose of 10 to 15 mCi is recommended. Although a strict low-iodine diet is unnecessary, iodine-rich foods should be avoided for at least 1 week before treatment. ATD should be stopped 3 to 7 days before RAI and may be resumed in select cases. Prophylactic glucocorticoids are recommended for patients with mildly active thyroid eye disease and may be considered for others at risk. Thyroid function should be monitored at 4–6 weeks post-treatment, every 2–3 months until stabilized, and then every 6–12 months. These guidelines highlight recent advances and underscore the importance of individualized treatment based on clinical features, comorbidities, and patient preferences in Korea.
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shinje Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyong Yeun Jung, Chan Kwon Jung, Yoon Young Cho, Dong-Jun Lim, Sun Wook Kim, Young Joo Park, Dong Gyu Na, Jee Soo Kim
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.
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.
Background Thyrotoxicosis presents significant diagnostic challenges in distinguishing Graves’ disease (GD) from destruction-induced thyrotoxicosis (DT) using ultrasound imaging. We evaluated a new technology, microvascular ultrasonography (MVUS) to effectively differentiate between GD and DT, and observe the MVUS changes during follow-up.
Methods A total of 264 consecutive patients were prospectively enrolled into two cohorts from August 2022 to March 2024 at one tertiary referral hospital: cohort 1 comprised patients initially presenting with thyrotoxicosis (n=185; 98 with GD and 87 with DT). Cohort 2 included patients either with GD considering antithyroid drug discontinuation or with DT in the follow-up phase after treatment (n=77). Ultrasound imaging was conducted using the MVUS technique, and the vascularity index (MVUS-VI) was automatically calculated as the percentage ratio of color pixels to total grayscale pixels within a specified region of interest.
Results Diagnostic accuracy highlighted MVUS-VI as the most accurate diagnostic tool, achieving a sensitivity of 79.6%, specificity of 84.3%, with an area under the curve of 0.856 (95% confidence interval, 0.800 to 0.911). Presence of thyroid peroxidase antibody or thyroglobulin antibody affected MVUS-VI’s performance, requiring a higher cut-off value for specificity in this subgroup. Follow-up in cohort 2 (n=77) demonstrated significant normalization in thyroid function and reductions in MVUS-VI from an initial 32.6%±23.4% to 20.8%±13.5% at follow-up (P<0.001).
Conclusion MVUS-VI provides a rapid, non-invasive diagnostic alternative to traditional methods in differentiating GD from DT, thus aiding in the management of patients with thyrotoxicosis.
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Update on newer ultrasound systems to study the microvasculature Orlando Catalano, Antonio Pio Masciotra La radiologia medica.2025;[Epub] CrossRef
Jinyoung Kim, Min-Hee Kim, Dong-Jun Lim, Hankyeol Lee, Jae Jun Lee, Hyuk-Sang Kwon, Mee Kyoung Kim, Ki-Ho Song, Tae-Jung Kim, So Lyung Jung, Yong Oh Lee, Ki-Hyun Baek
Endocrinol Metab. 2025;40(2):216-224. Published online January 13, 2025
Background This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules.
Methods This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images.
Results Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity.
Conclusion CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.
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.
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.
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Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
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.
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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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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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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.
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ISPAD
Clinical Practice Consensus Guidelines 2022: Management of the child, adolescent, and young adult with diabetes in limited resource settings
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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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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.
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Microvascular Ultrasonography Vascularity Index as a Rapid and Simplified Assessment Tool for Differentiating Graves’ Disease from Destructive Thyroiditis and Managing Thyrotoxicosis Han-Sang Baek, Chaiho Jeong, Jeonghoon Ha, Dong-Jun Lim Endocrinology and Metabolism.2025; 40(3): 394. CrossRef
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