Endocrinology and Metabolism

Original Articles

Fatty Liver Index Dynamics as a Predictor of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus and Non-Cirrhotic Livers: Eun-Hee Cho, Min Gu Kang, Chang Hun Lee, Shinyoung Oh, Chen Shen, Ha Ram Oh, Young Ran Park, Hyun Lee, Jong Seung Kim, Ji Hyun Park; Received December 15, 2024 Accepted March 13, 2025 Published online May 29, 2025; DOI: https://doi.org/10.3803/EnM.2024.2286 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Type 2 diabetes mellitus (T2DM) is a significant risk factor for hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease; however, surveillance strategies for patients with T2DM, especially without cirrhosis, are inadequate. This study examined whether the fatty liver index (FLI) and its dynamic changes can effectively identify patients with T2DM at increased risk for HCC.
Methods
Data from 92,761 individuals with T2DM aged 40 to 79 who underwent two health screenings (2012 to 2015) were analyzed. The FLI, calculated using waist circumference, body mass index, triglycerides, and gamma-glutamyl transferase, was used to stratify patients by baseline FLI and FLI changes between screenings. HCC cases were identified via International Classification of Diseases codes and reimbursement records (2016 to 2020).
Results
Patients with baseline FLI of 30 to 59.9 had a 1.90-fold higher risk (P<0.01) and those with FLI ≥60 had a 2.94-fold higher risk (P<0.01) of developing HCC compared to those with FLI <30. An increase in FLI from <30 to ≥30 resulted in a 2.10-fold higher risk of HCC (P<0.01), while a reduction in FLI from ≥30 to <30 led to a 0.64-fold lower risk (P=0.03). Protective benefits of FLI reduction took approximately 3 years to manifest.
Conclusion
Baseline and dynamic monitoring of FLI effectively identified HCC risk in T2DM patients with non-cirrhotic livers, supporting early detection and intervention.

Risk Stratification of Thyroid Nodules Diagnosed as Follicular Neoplasm on Core Needle Biopsy: Byeong-Joo Noh, Won Jun Kim, Jin Yub Kim, Ha Young Kim, Jong Cheol Lee, Myoung Sook Shim, Yong Jin Song, Kwang Hyun Yoon, In-Hye Jung, Hyo Sang Lee, Wooyul Paik, Dong Gyu Na; Received November 28, 2024 Accepted March 10, 2025 Published online May 28, 2025; DOI: https://doi.org/10.3803/EnM.2024.2256 [Epub ahead of print]

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This study assessed risk stratification and diagnostic performance for malignancy in thyroid nodules diagnosed as follicular neoplasm (FN) based on core needle biopsy (CNB) subcategories.
Methods
A total of 313 consecutive nodules (>1 cm) diagnosed as FN on CNB with corresponding surgical histology were included. FN subcategories were classified retrospectively for nodules diagnosed before 2022 (retrospective dataset) and prospectively for nodules diagnosed since 2022 (prospective dataset). CNB subcategories were determined using histologic criteria based on architectural uniformity and nuclear atypia, as modified from the 2019 Korean CNB pathology guideline. The diagnostic performance of CNB subcategories, nodule size, and ultrasound risk stratification systems (RSSs) for malignancy was assessed.
Results
CNB subcategory IVb showed a significantly higher malignancy risk compared to other subcategories in both datasets (34.5%–83.7% vs. 4.2%–13.6%, P<0.001). It was also identified as an independent predictor of malignancy in both datasets (P< 0.001), whereas nodule size and all ultrasound RSSs were not predictive of malignancy, including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (P≥0.079). CNB subcategory IVb demonstrated higher sensitivity for malignancy and a lower surgical rate for benign nodules compared to the nodule size criterion (>2 cm). The combined criterion of CNB subcategory IVb or nodule size >3 cm identified all malignant tumors, excluding NIFTP, in the prospective dataset.
Conclusion
CNB subcategory IVb effectively stratifies malignancy risk in thyroid nodules and outperforms nodule size (>2 cm) and ultrasound RSSs in diagnostic performance. Non-IVb nodules ≤3 cm can be safely managed with ultrasound surveillance instead of immediate surgery.

Clinical Outcomes of Follicular Thyroid Carcinoma Did Not Significantly Differ according to Tumor Size in an Iodine-Excessive Country: Da Eun Leem, Ji Hyun Yoo, Bo Ram Kim, Jung Sun Kim, Tae Hyuk Kim, Sun Wook Kim, Yun Jae Chung, Jae Hoon Chung, Young Lyun Oh; Received January 19, 2025 Accepted March 24, 2025 Published online May 26, 2025; DOI: https://doi.org/10.3803/EnM.2025.2324 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
Follicular thyroid carcinoma (FTC) measuring <2 cm is generally associated with good prognosis, while tumor size ≥4 cm is regarded as being associated with a poor prognosis. This study aimed to evaluate FTC prognosis by tumor size to investigate whether the 2- and 4-cm criteria are appropriate for assessing prognosis.
Methods
Data of 248 patients with FTC diagnosed between August 1995 and June 2021 were retrospectively analyzed. The population was divided into four groups according to tumor size: <2.0, 2.0–3.9, 4.0–5.9, and ≥6.0 cm. Distant metastasis (DM), recurrence and/or structural persistence (R/SP), cancer-specific death (CSD), and frequency of telomerase reverse transcriptase (TERT) promoter mutations based on tumor size were evaluated.
Results
While the rates of DM, R/SP, and CSD and the frequency of TERT promoter mutations did not differ among the size groups <6 cm, they increase sharply in tumor size ≥6 cm, although statistically insignificant (P=0.608, P=0.248, P=0.089, and P=0.165 respectively). Widely invasive subtypes, and TERT promoter mutations were significantly associated with DM (P=0.009 and P<0.001, respectively). Age ≥55 years, gross extrathyroidal extension, synchronous DM, and TERT promoter mutation were independent risk factors for CSD (P=0.005, P=0.003, P<0.001, and P=0.002, respectively).
Conclusion
DM, R/SP, CSD, and TERT promoter mutations were not uncommon in FTCs <2 cm compared to those in larger FTCs, whereas FTCs ≥6 cm showed a sharp decline in prognosis, although this was statistically insignificant.

Brief Report

Causal Associations of Cardiovascular Proteins and Diabetic Nephropathy Revealed by Mediation and Phenome-Wide Mendelian Randomization: Lei Chen, Yongdi Zuo, Manrong He, Jingxue Du, Wanxin Tang; Received October 15, 2024 Accepted January 23, 2025 Published online May 19, 2025; DOI: https://doi.org/10.3803/EnM.2024.2207 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Cardiovascular factors play a critical role in the progression of diabetic nephropathy (DN). This study utilized Mendelian randomization analysis to explore the causal relationships among cardiovascular proteins, risk factors, and DN. Using cis-protein quantitative trait loci (cis-pQTL) data for 90 cardiovascular proteins, we identified C-X3-C motif chemokine ligand 1 (CX3CL1) and colony-stimulating factor-1 (CSF-1) as potential therapeutic targets for DN. CX3CL1 was found to increase DN risk through mechanisms involving body mass index, fasting insulin, and hypertension. Conversely, CSF-1 appeared to protect against DN by reducing the number of monocytes expressing high levels of human leukocyte antigen. Additionally, targeting CX3CL1 could lower the risk of DN as well as other conditions, including acute renal injury, pituitary disorders, and necrotizing vasculopathies. These results highlight CX3CL1 and CSF-1 as promising novel therapeutic targets for DN.

Original Articles

Synthetic Data-Enhanced Classification of Prevalent Osteoporotic Fractures Using Dual-Energy X-Ray Absorptiometry-Based Geometric and Material Parameters: Luca Quagliato, Jiin Seo, Jiheun Hong, Taeyong Lee, Yoon-Sok Chung; Received October 22, 2024 Accepted January 8, 2025 Published online May 14, 2025; DOI: https://doi.org/10.3803/EnM.2024.2211 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
Bone fracture risk assessment for osteoporotic patients is essential for implementing early countermeasures and preventing discomfort and hospitalization. Current methodologies, such as Fracture Risk Assessment Tool (FRAX), provide a risk assessment over a 5- to 10-year period rather than evaluating the bone’s current health status.
Methods
The database was collected by Ajou University Medical Center from 2017 to 2021. It included 9,260 patients, aged 55 to 99, comprising 242 femur fracture (FX) cases and 9,018 non-fracture (NFX) cases. To model the association of the bone’s current health status with prevalent FXs, three prediction algorithms—extreme gradient boosting (XGB), support vector machine, and multilayer perceptron—were trained using two-dimensional dual-energy X-ray absorptiometry (2D-DXA) analysis results and subsequently benchmarked. The XGB classifier, which proved most effective, was then further refined using synthetic data generated by the adaptive synthetic oversampler to balance the FX and NFX classes and enhance boundary sharpness for better classification accuracy.
Results
The XGB model trained on raw data demonstrated good prediction capabilities, with an area under the curve (AUC) of 0.78 and an F1 score of 0.71 on test cases. The inclusion of synthetic data improved classification accuracy in terms of both specificity and sensitivity, resulting in an AUC of 0.99 and an F1 score of 0.98.
Conclusion
The proposed methodology demonstrates that current bone health can be assessed through post-processed results from 2D-DXA analysis. Moreover, it was also shown that synthetic data can help stabilize uneven databases by balancing majority and minority classes, thereby significantly improving classification performance.

Safety and Effectiveness of Pravastatin in Korean Patients with Dyslipidemia Based on the Cardiovascular Risk Classification: Pooled Analysis of Four Observational Studies: In-Kyung Jeong, Hyuk-Sang Kwon, Dae Jung Kim, Sin Gon Kim; Received October 2, 2024 Accepted February 17, 2025 Published online April 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2200 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Despite their efficacy, statin-related adverse events (AEs) may interfere with statin treatment and contribute to negative outcomes in patients with cardiovascular diseases. In this study, we evaluated the safety and effectiveness of pravastatin in Korea.
Methods
Pooled data were collected from four multicenter prospective observational studies conducted in Korea between 2011 and 2020. Finally, 7,334 and 2,022 participants were included in the safety and effectiveness analyses, respectively. Overall safety, particularly muscle-related, incidence of new-onset diabetes mellitus (DM), changes in fasting plasma glucose and hemoglobin A1c level, achievement of target low-density lipoprotein cholesterol (LDL-C) level, and changes in LDL-C level were analyzed.
Results
At week 24, after 20 or 40 mg pravastatin treatment, safety results showed that AEs and adverse drug reactions (ADRs) were 8.7% and 1.3%, respectively, and that muscle-related AEs and ADRs were 0.5% and 0.3%, respectively, with no statistically significant difference in risk factors for statin-associated muscle symptoms. No patients developed DM during the study period. Additionally, at week 24, the achievement rates of target LDL-C levels were 87.9%, 78.4%, 57.8%, and 11.6% in low-, moderate-, high-, and very high-risk groups, respectively.
Conclusion
This study found that 20 or 40 mg pravastatin had minimal side effects and was safe for use in real-world clinical settings in Korea. Specifically, these doses effectively achieved the target LDL-C levels in patients with dyslipidemia in low-, moderate-, and high-risk groups for atherosclerotic cardiovascular disease (ASCVD). These results demonstrate that pravastatin can be safely administered continuously to patients with low-, moderate-, and high-risk ASCVD in a real-world clinical setting.

Comprehensive Proteomics and Machine Learning Analysis to Distinguish Follicular Adenoma and Follicular Thyroid Carcinoma from Indeterminate Thyroid Nodules: Hee-Sung Ahn, Eyun Song, Chae A Kim, Min Ji Jeon, Yu-Mi Lee, Tea-Yon Sung, Dong Eun Song, Jiyoung Yu, Ji Min Shin, Yeon-Sook Choi, Kyunggon Kim, Won Gu Kim; Received October 16, 2024 Accepted February 24, 2025 Published online April 10, 2025; DOI: https://doi.org/10.3803/EnM.2024.2208 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The preoperative diagnosis of follicular thyroid carcinoma (FTC) is challenging because it cannot be readily distinguished from follicular adenoma (FA) or benign follicular nodular disease (FND) using the sonographic and cytological features typically employed in clinical practice.
Methods
We employed comprehensive proteomics and machine learning (ML) models to identify novel diagnostic biomarkers capable of classifying three subtypes: FTC, FA, and FND. Bottom-up proteomics techniques were applied to quantify proteins in formalin-fixed, paraffin-embedded (FFPE) thyroid tissues. In total, 202 FFPE tissue samples, comprising 62 FNDs, 72 FAs, and 68 FTCs, were analyzed.
Results
Close spectrum-spectrum matching quantified 6,332 proteins, with approximately 9% (780 proteins) differentially expressed among the groups. When applying an ML model to the proteomics data from samples with preoperative indeterminate cytopathology (n=183), we identified distinct protein panels: five proteins (CNDP2, DNAAF5, DYNC1H1, FARSB, and PDCD4) for the FND prediction model, six proteins (DNAAF5, FAM149B1, RPS9, TAGLN2, UPF1, and UQCRC1) for the FA model, and seven proteins (ACTN4, DSTN, MACROH2A1, NUCB1, SPTAN1, TAGLN, and XRCC5) for the FTC model. The classifiers’ performance, evaluated by the median area under the curve values of the random forest models, was 0.832 (95% confidence interval [CI], 0.824 to 0.839) for FND, 0.826 (95% CI, 0.817 to 0.835) for FA, and 0.870 (95% CI, 0.863 to 0.877) for FTC.
Conclusion
Quantitative proteome analysis combined with an ML model yielded an optimized multi‐protein panel that can distinguish FTC from benign subtypes. Our findings indicate that a proteomic approach holds promise for the differential diagnosis of FTC.

Review Article

Thyroid
Ultrasound Imaging Criteria and Protocols for Active Surveillance of Low-Risk Thyroid Cancer: A Review of International Consensus Guidelines: Ji Ye Lee, Dong Gyu Na; Endocrinol Metab. 2025;40(2):185-194. Published online March 27, 2025; DOI: https://doi.org/10.3803/EnM.2024.2319

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Abstract PDF PubReader ePub: Given the indolent nature and favorable outcomes of papillary thyroid microcarcinoma (PTMC), active surveillance (AS) has been adopted as an alternative management option to immediate surgery. However, the meticulous selection of patients based on individual and tumor-specific characteristics, as well as ultrasound (US) findings, is crucial in AS. Regular US monitoring is performed during AS to detect indicators of tumor progression, such as growth, the emergence of new US features suggestive of gross extrathyroidal extension, and lymph node metastasis. Thus, imaging-based evaluations play a pivotal role in guiding the decision to continue AS or proceed with surgical intervention. This review introduces the Korean Society of Thyroid Radiology (KSThR) guideline for the standardized US imaging of patients with low-risk PTMC under AS, which provide practical recommendations for tumor assessment during the initiation and follow-up phases of AS. This review compared the key features of the KSThR guideline with those of major international guidelines and identified the similarities and differences in imaging methodologies and follow-up strategies. The primary objective of this review is to support the broader implementation of AS and improve outcomes for patients with low-risk PTMC by emphasizing imaging protocols.

Original Articles

⁶⁸Ga-DOTATOC PET/CT in the Localization of Pituitary Tumors in Cushing’s Disease: Kyungwon Kim, Dongwoo Kim, Min-Ho Lee, Yae Won Park, Sung Soo Ahn, Ju Hyung Moon, Eui Hyun Kim, Sun Ho Kim, Cheol Ryong Ku, Eun Jig Lee; Received November 20, 2024 Accepted January 21, 2025 Published online March 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2249 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
This study aimed to determine the value of ⁶⁸Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) in localizing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas.
Methods
In this retrospective cohort study, we enrolled 30 patients with Cushing’s disease and positive ACTH immunoreactivity. All patients underwent ⁶⁸Ga-DOTATOC PET/CT and pituitary magnetic resonance imaging (MRI) before transsphenoidal adenomectomy.
Results
Twenty-five patients showed ⁶⁸Ga-DOTATOC uptake in their pituitary glands on PET/CT. Median age, pre-operative ACTH levels, pre-operative cortisol, and tumor size on MRI were comparable irrespective of DOTATOC uptake. ⁶⁸Ga-DOTATOC PET/CT showed a 77% success rate for localizing adenomas, which was not statistically different from that of MRI. The ACTH level in the successful localization group was significantly higher than that in the failed group (84.41 pg/mL vs. 37.26 pg/mL, P=0.001). The ACTH level was statistically significant predictor of successful localization using ⁶⁸Ga-DOTATOC PET/CT (P=0.013). The area under the curve was 0.932 with a cutoff of 53.86 pg/mL for ACTH levels to determine successful localization. Pre-operative ACTH levels above 53.86 pg/mL showed the best diagnostic accuracy in predicting the success of localizing adenomas (sensitivity, 91.3%; specificity, 85.7%). Mean and maximum standardized uptake value of adenoma negatively correlated to pre-operative ACTH level.
Conclusion
Plasma ACTH level is a favorable predictor for the successful localization and negative correlation with ⁶⁸Ga-DOTATOC uptake of corticotroph adenomas in ⁶⁸Ga-DOTATOC PET/CT. ⁶⁸Ga-DOTATOC PET/CT did not improve tumor localization for Cushing’s disease compared with MRI alone.

Medullary Thyroid Carcinoma Detected by Routine Health Screening Had Better Clinical Outcome and Survival: Ji Hyun Yoo, Da Eun Leem, Bo Ram Kim, Tae Hyuk Kim, Sun Wook Kim, Jae Hoon Chung; Received October 22, 2024 Accepted January 8, 2025 Published online March 5, 2025; DOI: https://doi.org/10.3803/EnM.2024.2214 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The benefits of early detection in medullary thyroid carcinoma (MTC) are not well established. This study investigates the impact of early detection of MTC on clinical outcomes.
Methods
This retrospective study evaluated 144 patients diagnosed with MTC at Samsung Medical Center between 1995 and 2019, classified as asymptomatic (mostly detected through routine health check-ups, including ultrasonography, calcitonin, or carcinoembryonic antigen levels) and symptomatic. Initial treatment response, final clinical outcomes, and cancer-specific survival were compared.
Results
MTC was diagnosed in 104 (72.2%) asymptomatic and 40 (27.8%) symptomatic patients. The symptomatic group showed a significantly larger primary tumor size, more frequent lateral neck lymph node metastasis, more advanced tumor, node, metastasis (TNM) staging, and higher pre- and postoperative serum calcitonin levels. For initial treatment response, the proportion of excellent responders was significantly higher in the asymptomatic group (71.2% vs. 40.0%), while that of patients with biochemical incomplete response (37.5% vs. 26.9%) and structural incomplete response (22.5% vs. 1.9%) was significantly higher in the symptomatic group (all P<0.001). For the final clinical outcomes, the rate of patients with no evidence of disease was higher in the asymptomatic group (67.3% vs. 30.0%), while the rate of patients with structurally identifiable disease was higher in the symptomatic group (45.0% vs. 7.7%) (P<0.001 for both). The symptomatic group had significantly poorer cancer-specific survival than the asymptomatic group (log-rank P=0.023).
Conclusion
Compared with late diagnosis through symptomatic presentation, early diagnosis in asymptomatic patients results in significantly better initial treatment response, final clinical outcomes, and cancer-specific survival in patients with MTC.

Association between the Triglyceride-Glucose Index and Cardiovascular Risk and Mortality across Different Diabetes Durations: A Nationwide Cohort Study: Jeongeun Kwak, Kyung-Do Han, Eun Young Lee, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Jeongmin Lee; Received October 15, 2024 Accepted January 3, 2025 Published online March 5, 2025; DOI: https://doi.org/10.3803/EnM.2024.2205 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: 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.

Diabetes, obesity and metabolism
Plasma C-Peptide Levels and the Continuous Glucose Monitoring-Defined Coefficient of Variation in Risk Prediction for Hypoglycemia in Korean People with Diabetes Having Normal and Impaired Kidney Function: So Yoon Kwon, Jiyun Park, So Hee Park, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Sang-Man Jin; Endocrinol Metab. 2025;40(2):268-277. Published online February 27, 2025; DOI: https://doi.org/10.3803/EnM.2024.2083

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Abstract PDF Supplementary Material PubReader ePub

Background
We aimed to investigate the predictive values of plasma C-peptide levels and the continuous glucose monitoring (CGM)-defined coefficient of variation (CV) in risk prediction for hypoglycemia in Korean people with diabetes with normal and impaired kidney function.
Methods
We analyzed data from 1,185 participants diagnosed with type 1 and type 2 diabetes who underwent blinded professional CGM between January 2009 and May 2021 at outpatient clinics. We explored correlations among CGM-defined CV, plasma C-peptide levels, and time below range at <70 and 54 mg/dL across different kidney function categories.
Results
In patients with chronic kidney disease (CKD) stages 1–2 (n=934), 89.3% who had a random plasma C-peptide level higher than 600 pmol/L exhibited a CV of ≤36%. Among those in CKD stage 3 (n=161) with a random plasma C-peptide level exceeding 600 pmol/L, 66.7% showed a CV of ≤36%. In stages 4–5 of CKD (n=90), the correlation between random C-peptide levels and CV was not significant (r=–0.05, P=0.640), including cases with a CV greater than 36% despite very high random plasma C-peptide levels. Random plasma C-peptide levels and CGM-assessed CV significantly predicted hypoglycemia in CKD stages 1–2 and 1–5, respectively.
Conclusion
The established C-peptide criteria in Western populations are applicable to Korean people with diabetes for hypoglycemic risk prediction, unless kidney function is impaired equivalent to CKD stage 3–5. The CGM-defined CV is informative for hypoglycemic risk prediction regardless of kidney function.

Citations

Citations to this article as recorded by

Plasma C-Peptide Level and Continuous Glucose Monitoring-Derived Coefficient of Variation as a Predictable Risk Factor for Hypoglycemia in Koreans with Diabetes
Seung-Hyun Ko
Endocrinology and Metabolism.2025; 40(2): 198. CrossRef
Beneficial Role of Increased Glucose Infusion in Decompensated Type 2 Diabetes Patient
Marie Ticha, Ondrej Sobotka, Pavel Skorepa, Lubos Sobotka
Diabetology.2025; 6(6): 47. CrossRef

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; Received October 12, 2024 Accepted December 2, 2024 Published online February 25, 2025; DOI: https://doi.org/10.3803/EnM.2024.2206 [Epub ahead of print]

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Abstract PDF PubReader ePub: 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.

Prognostic Impact of Primary Tumor Size in Papillary Thyroid Carcinoma without Lymph Node Metastasis: Chae A Kim, Hye In Kim, Na Hyun Kim, Tae Yong Kim, Won Bae Kim, Jae Hoon Chung, Min Ji Jeon, Tae Hyuk Kim, Sun Wook Kim, Won Gu Kim; Received October 2, 2024 Accepted January 2, 2025 Published online February 25, 2025; DOI: https://doi.org/10.3803/EnM.2024.2199 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
We aimed to investigate the prognostic significance of primary tumor size in patients with pT1–T3a N0 M0 papillary thyroid carcinoma (PTC), minimizing the impact of confounding factors.
Methods
A multicenter retrospective study included 5,759 patients with PTC. Those with lymph node metastasis, gross extrathyroidal extension (ETE), and aggressive variants were excluded. Patients were categorized by primary tumor size (≤1, 1.1–2, 2.1–4, and >4 cm) and subdivided based on the presence of microscopic ETE (mETE).
Results
The median age was 48.0 years, and 87.5% were female. The median primary tumor size was 0.7 cm, with mETE identified in 43.7%. The median follow-up was 8.0 years, with an overall recurrent/persistent disease rate of 2.8%. Multivariate analysis identified male sex, larger tumor size, and the presence of mETE as significant prognostic risk factors. The 10-year recurrent/persistent disease rates for tumors ≤1, 1.1–2, 2.1–4, and >4 cm were 2.5%, 4.7%, 11.1%, and 6.0%, respectively. The 2.1–4 cm group had a significantly higher hazard ratio (HR), with the >4 cm group had the highest HR than the ≤1 cm group. Patients with mETE had a higher recurrent/persistent disease rate (4.5%) than those without, with rates by tumor size being 2.6%, 5.6%, 16.7%, and 8.2%.
Conclusion
Larger tumor size and the presence of mETE significantly increased the risk of recurrent/persistent disease in PTC. Patients with pT2–T3a N0 M0 PTC (>2 cm) had a recurrent/persistent disease risk exceeding 5%, warranting vigilant management.

Prevalence of Mortality and Vascular Complications in Older Patients with Diabetes in Korea: Kwang Joon Kim, Jeongmin Lee, Yang Sun Park, Yong-ho Lee, Kyeong Hye Park, Hee-Won Jung, Chang Oh Kim, Man Young Park, Hun-Sung Kim, Bong-Soo Cha; Received September 9, 2024 Accepted January 2, 2025 Published online February 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2173 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: 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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