Endocrinology and Metabolism

Original Article

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: 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

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; Received January 21, 2025 Accepted February 11, 2025 Published online March 27, 2025; DOI: https://doi.org/10.3803/EnM.2024.2319 [Epub ahead of print]

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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

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.

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.

Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP): Jae Hoon Moon, Eun Kyung Lee, Wonjae Cha, Young Jun Chai, Sun Wook Cho, June Young Choi, Sung Yong Choi, A Jung Chu, Eun-Jae Chung, Yul Hwangbo, Woo-Jin Jeong, Yuh-Seog Jung, Kyungsik Kim, Min Joo Kim, Su-jin Kim, Woochul Kim, Yoo Hyung Kim, Chang Yoon Lee, Ji Ye Lee, Kyu Eun Lee, Young Ki Lee, Hunjong Lim, Do Joon Park, Sue K. Park, Chang Hwan Ryu, Junsun Ryu, Jungirl Seok, Young Shin Song, Ka Hee Yi, Hyeong Won Yu, Eleanor White, Katerina Mastrocostas, Roderick J. Clifton-Bligh, Anthony Glover, Matti L. Gild, Ji-hoon Kim, Young Joo Park; Received August 9, 2024 Accepted November 29, 2024 Published online February 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2136 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Prognostic Indicators and Comparative Treatment Outcomes in High-Risk Thyroid Cancer with Laryngotracheal Invasion: Eman A. Toraih, Jessan A. Jishu, Mohammad H. Hussein, Aly A. M. Shaalan, Manal S. Fawzy, Emad Kandil; Received May 9, 2024 Accepted October 18, 2024 Published online January 22, 2025; DOI: https://doi.org/10.3803/EnM.2024.2033 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Laryngotracheal invasion occurs in a subset of patients with well-differentiated thyroid cancer (WDTC) and is associated with a poor prognosis. We aimed to analyze patterns and predictors/outcomes related to this high-risk manifestation.
Methods
This population-based analysis utilized the Surveillance, Epidemiology, and End Results (SEER) registry (2000 to 2015) to identify WDTC patients. Temporal trends and geographic variation in invasion rates were assessed. Logistic regression and propensity score matching were employed to identify predictors of secondary malignancy, mortality, and treatment impact on overall and thyroid cancer (TC)-specific survival.
Results
Of 131,721 WDTC patients, 1,662 (1.3%) had tracheal invasion and 976 (0.7%) had laryngeal invasion at diagnosis. Tracheal and laryngeal invasion rates declined from 3.7%–0.7% and 1.5%–0.6%, respectively, from 2000 to 2015. Compared to 98,835 noninvasive cases, patients with laryngotracheal invasion were older and more often male, Asian, and Hispanic (all P<0.001). This group had larger tumors with higher rates of nodal (N1: 61.8% vs. 15.1%) and distant metastases (M1: 9.3% vs. 0.4%). Age ≥55 years (hazard ratio [HR], 1.19; P=0.004) and metastases (HR, 1.75; P<0.001) increased TC-specific mortality, whereas the converse pattern was found for Asian race (HR, 0.63; P=0.002) and surgery (HR, 0.35; P<0.001). In rigorously matched groups to control confounding, adding radioactive iodine to surgery reduced mortality by 30% (P<0.001). However, external beam radiation and systemic therapy did not improve survival over surgery alone.
Conclusion
Laryngotracheal invasion is present in 0.7% to 1.3% of cases, conferring over double the mortality risk. Radioactive iodine with surgery improves outcomes in this aggressive WDTC subset.

Diabetes, obesity and metabolism
Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis: A.B.M. Kamrul-Hasan, Muhammad Shah Alam, Deep Dutta, Thanikai Sasikanth, Fatema Tuz Zahura Aalpona, Lakshmi Nagendra; Endocrinol Metab. 2025;40(1):112-124. Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2164

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Abstract PDF Supplementary Material PubReader ePub: Background
Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide.
Methods
RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups.
Results
Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma.
Conclusion
Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk.

Risk of Osteoporotic Fractures among Patients with Thyroid Cancer: A Nationwide Population-Based Cohort Study: Eu Jeong Ku, Won Sang Yoo, Yu Been Hwang, Subin Jang, Jooyoung Lee, Shinje Moon, Eun Kyung Lee, Hwa Young Ahn; Received July 13, 2024 Accepted November 11, 2024 Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2101 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The associations between thyroid cancer and skeletal outcomes have not been thoroughly investigated. We aimed to investigate the risk of osteoporotic fractures in patients with thyroid cancer compared to that in a matched control group.
Methods
This retrospective cohort study included 2,514 patients with thyroid cancer and 75,420 matched controls from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC, 2006–2019). The rates of osteoporotic fractures were analyzed, and associations with the levothyroxine dose were evaluated.
Results
Patients with thyroid cancer had a significantly lower risk of fracture than did the control group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69 to 0.94; P=0.006). Patients diagnosed with thyroid cancer after the age of 50 years (older cancer group) had a significantly lower risk of fracture than did those in the control group (HR, 0.72; 95% CI, 0.6 to 0.85; P<0.001), especially those diagnosed with spinal fractures (HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). Patients in the older cancer group started osteoporosis treatment earlier than did those in the control group (65.5±7.5 years vs. 67.3±7.6 years, P<0.001). Additionally, a lower dose of levothyroxine was associated with a reduced risk of fractures.
Conclusion
In the clinical setting, the risk of fracture in women diagnosed with thyroid cancer after the age of 50 years was lower than that in the control group, which was caused by more proactive osteoporosis treatment in postmenopausal women with thyroid cancer.

Deep Learning Technology for Classification of Thyroid Nodules Using Multi-View Ultrasound Images: Potential Benefits and Challenges in Clinical Application: 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; Received June 3, 2024 Accepted September 23, 2024 Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2058 [Epub ahead of print]

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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.

Thyroid
Triiodothyronine Is Associated with Incidence/Resolution of Steatotic Liver Disease: Longitudinal Study in Euthyroid Korean: Hye In Kim, Jun Young Kim, Jung Hwan Cho, Ji Min Han, Sunghwan Suh, Ji Cheol Bae, Tae Hyuk Kim, Sun Wook Kim, Jong Ryeal Hahm, Jae Hoon Chung; Endocrinol Metab. 2025;40(1):135-145. Published online December 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.2040

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The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design.
Methods
This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models.
Results
During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD.
Conclusion
In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Thyroid
Association of the Preoperative Controlling Nutritional Status (CONUT) Score with Clinicopathological Characteristics in Patients with Papillary Thyroid Carcinoma: Doohwa Kim, Myungsoo Im, Soree Ryang, Mijin Kim, Yun Kyung Jeon, Sang Soo Kim, Bo Hyun Kim; Endocrinol Metab. 2024;39(6):856-863. Published online November 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.2006

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Abstract PDF Supplementary Material PubReader ePub: Background
The Controlling Nutritional Status (CONUT) score is an immunonutritional test tool based on serum albumin, total cholesterol, and lymphocyte counts. It has been studied as a simple prognostic predictor for various carcinomas. This study aimed to investigate the association between preoperative CONUT scores and the clinicopathological characteristics in papillary thyroid carcinoma (PTC) patients.
Methods
This study included 2,403 PTC patients who underwent total thyroidectomy between 2012 and 2016 at a single tertiary medical center. The CONUT scores were calculated based on preoperative blood tests. The clinicopathological characteristics were retrospectively reviewed. The patients were categorized by the CONUT score (relatively low, 0–2; relatively high, 3–5).
Results
Among the 2,997 PTC patients who underwent total thyroidectomy at Pusan National University Hospital between 2012 and 2016, those without preoperative blood test were excluded (n=149). Finally 2,403 patients were analyzed after excluding 439 patients taking lipid-lowering drugs and six patients without available T stage data after surgery. Based on the CONUT score, the relatively high score group had a lower body mass index (23.7±3.3 kg/m² vs. 21.9±2.9 kg/m², P<0.001), more advanced T stage (T stage 3/4, 5.9% vs. 11.4%, P=0.045), and higher extrathyroidal extension (2.1% vs. 7.6%, P=0.005).
Conclusion
Patients included in this large, single-center study all had a preoperative CONUT score of 0–5, but this study demonstrated that higher preoperative CONUT scores were significantly associated with advanced T stage and extrathyroidal extension. The CONUT score, which can be easily used in clinical practice, is thought to be helpful in predicting the aggressiveness of PTC.

Thyroid
A Neglected Point: Frailty in Older Adults with Differentiated Thyroid Cancer: Meric Coskun, Esra Cataltepe, Hacer Dogan Varan, Eda Ceker, Yasemin Bektas, Yasemin Kuscu, Mehmet Muhittin Yalcin, Mujde Akturk, Fusun Balos Toruner, Mehmet Ayhan Karakoc, Alev Eroglu Altinova; Endocrinol Metab. 2024;39(6):899-907. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2046

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This study investigated the risk of frailty in older adults with differentiated thyroid cancer (DTC) and the effect of thyroid- stimulating hormone (TSH) levels on frailty.
Methods
This single-center, cross-sectional study included 70 DTC patients aged ≥60 years with stable TSH levels during the previous year while receiving levothyroxine. Frailty was assessed using the fried frailty phenotype (FFP). Anterior thigh muscle thickness was measured by ultrasound, and the sonographic thigh adjustment ratio (STAR) index was calculated. Muscle strength was measured using a hand dynamometer. Physical activity was determined by the physical activity scale for the elderly (PASE).
Results
The median (interquartile range) age and follow-up time were 65 years (62 to 71) and 11 years (7.0 to 14.2), respectively. The median TSH level was 1.10 μIU/mL (0.49 to 1.62), and 58.6% of patients were prefrail/frail. Muscle mass and strength were reduced in 35.7% and 17.2% of patients, respectively. TSH levels were lower in those with prefrailty/frailty (P=0.002), low muscle mass (P=0.014), and low strength (P=0.037) than in their normal counterparts. TSH levels correlated negatively with FFP (P= 0.001) and positively with the STAR index (P=0.034). TSH below 1.325 μIU/mL was associated with an increased frailty risk (area under the curve=0.719; P=0.001). Low TSH, female sex, low handgrip strength, and low PASE leisure time scores emerged as independent predictors of frailty (P<0.05).
Conclusion
Older adults with lower TSH levels due to DTC are at high frailty risk and have low muscle mass and strength. Therefore, TSH targets should be set based on a comprehensive evaluation with consideration of the risk-benefit ratio.

Thyroid
Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma: Moon Young Oh, Kyong Yeun Jung, Hoonsung Choi, Young Jun Chai, Sun Wook Cho, Su-jin Kim, Kyu Eun Lee, Eun-Jae Chung, Do Joon Park, Young Joo Park, Han-Kwang Yang; Endocrinol Metab. 2024;39(6):877-890. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2027

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Abstract PDF Supplementary Material PubReader ePub: Background
Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.
Methods
Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed.
Results
The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group.
Conclusion
Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.

Thyroid
Prevalence of Subclinical Hypothyroidism in a Non-Diabetic Young Female Population and Its Impact on Diabetes and Cardiometabolic Risk: Nawoda Hewage, Udaya Wijesekara, Rasika Perera; Endocrinol Metab. 2024;39(6):864-876. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2015

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We evaluated the influence of subclinical hypothyroidism (SCH) on insulin resistance (IR), cardiometabolic risk, and obesity in childbearing-age women without diabetes.
Methods
This cross-sectional investigation included 282 women, aged 18 to 35 years, from rural and suburban Sri Lanka. Anthropometric and biochemical parameters, including IR and lipid/thyroid profiles, were recorded. Data were compared between SCH and euthyroidism (EU) for controls (normal weight) and cases (overweight/obese).
Results
The overall rates of SCH, EU, IR, and metabolic syndrome (MetS) were 40.42%, 59.57%, 73.40%, and 24.46%, respectively. Both controls and cases included individuals with SCH; overall, 168 participants (59.57%) had EU, while 114 (40.42%) exhibited SCH. IR was significantly associated with SCH in both weight groups (P<0.05). Among those with SCH, the odds ratios (ORs) for IR were >2 (95% confidence interval [CI], 0.45 to 3.87) in controls and >6 (95% CI, 3.52 to 8.41) in cases. Similarly, the ORs for MetS were >1 (95% CI, 0.38 to 4.16) in controls and >11 (95% CI, 8.73 to 15.01) in cases. Dyslipidemia and hypertriglyceridemia were significantly more prevalent in the SCH group (P<0.05). Women with SCH exhibited higher mean values for all obesity indices compared to their EU counterparts, surpassing normal thresholds (P<0.05). Among obesity measures, visceral adiposity index (VAI) demonstrated the highest area under the curve and sensitivity for assessing SCH and cardiovascular disease (CVD) risk.
Conclusion
SCH must be identified and managed in young women to help prevent diabetes and cardiometabolic disorders. VAI may aid in precisely detecting SCH and CVD.

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