Endocrinology and Metabolism

Articles in E-pub version are posted online ahead of regular printed publication.

Editorial

Trends in Thyroid Cancer Mortality Rates in Korea: Insights from National Health Database: Won Gu Kim; Received November 25, 2024 Accepted December 6, 2024 Published online December 11, 2024; DOI: https://doi.org/10.3803/EnM.2024.2251 [Epub ahead of print]

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Original Articles

Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility: Daham Kim, Yoon Hee Cho, Min Jeong Kang, So Jeong Lee, Soohyun Lee, Bo Hyon Yun, Hyunjin Chi, Jeongsuk An, Kyungsun Lee, Jaekyu Han, Susan Chi, Moo Young Song, Sang-Hoon Cha, Eun Jig Lee; Received July 4, 2024 Accepted September 11, 2024 Published online December 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.2090 [Epub ahead of print]

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Abstract PDF: Background
Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function.
Methods
SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test.
Results
The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight.
Conclusion
These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.

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; Received May 11, 2024 Accepted July 19, 2024 Published online December 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.2040 [Epub ahead of print]

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Abstract PDF: Background
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.

Carnitine Metabolite as a Potential Circulating Biomarker for Sarcopenia in Men: Je Hyun Seo, Jung-Min Koh, Han Jin Cho, Hanjun Kim, Young‑Sun Lee, Su Jung Kim, Pil Whan Yoon, Won Kim, Sung Jin Bae, Hong-Kyu Kim, Hyun Ju Yoo, Seung Hun Lee; Received July 28, 2024 Accepted October 7, 2024 Published online November 28, 2024; DOI: https://doi.org/10.3803/EnM.2024.2117 [Epub ahead of print]

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Abstract PDF: Background
Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia.
Methods
Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort.
Results
An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027).
Conclusion
C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Metabolic Phenotypes of Women with Gestational Diabetes Mellitus Affect the Risk of Adverse Pregnancy Outcomes: Joon Ho Moon, Sookyung Won, Hojeong Won, Heejun Son, Tae Jung Oh, Soo Heon Kwak, Sung Hee Choi, Hak Chul Jang; Received July 10, 2024 Accepted September 23, 2024 Published online November 28, 2024; DOI: https://doi.org/10.3803/EnM.2024.2089 [Epub ahead of print]

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Abstract PDF: Background
Gestational diabetes mellitus (GDM) affects women with diverse pathological phenotypes, but little is known about the effects of this variation on perinatal outcomes. We explored the metabolic phenotypes of GDM and their impact on adverse pregnancy outcomes.
Methods
Women diagnosed with gestational glucose intolerance or GDM were categorized into subgroups according to their prepregnancy body mass index (BMI) and the median values of the gestational Matsuda and Stumvoll indices. Logistic regression analysis was employed to assess the odds of adverse pregnancy outcomes, such as large-for-gestational age (LGA), small-for-gestational age, preterm birth, low Apgar score, and cesarean section.
Results
A total of 309 women were included, with a median age of 31 years and a median BMI of 22.3 kg/m². Women with a higher pre-pregnancy BMI had a higher risk of LGA newborns (adjusted odds ratio [aOR] for pre-pregnancy BMI ≥25 kg/m² compared to 20–23 kg/m², 4.26; 95% confidence interval [CI], 1.99 to 9.12; P<0.001; P for trend=0.001), but the risk of other adverse pregnancy outcomes did not differ according to pre-pregnancy BMI. Women with insulin resistance had a higher risk of LGA (aOR, 1.88; 95% CI, 1.02 to 3.47; P=0.043) and cesarean section (aOR, 2.12; 95% CI, 1.29 to 3.50; P=0.003) than women in the insulin-sensitive group. In contrast, defective β-cell function did not affect adverse pregnancy outcomes.
Conclusion
Different metabolic phenotypes of GDM were associated with heterogeneous pregnancy outcomes. Women with obesity and those with insulin resistance are at greater risk of adverse outcomes and might need strict glycemic management during pregnancy.

Comparison of Population Attributable Fractions of Cancer Incidence and Mortality Linked to Excess Body Weight in Korea from 2015 to 2030: Youjin Hong, Jihye An, Jeehi Jung, Hyeon Sook Lee, Soseul Sung, Sungji Moon, Inah Kim, Jung Eun Lee, Aesun Shin, Sun Ha Jee, Sun-Seog Kweon, Min-Ho Shin, Sangmin Park, Seung-Ho Ryu, Sun Young Yang, Seung Ho Choi, Jeongseon Kim, Sang-Wook Yi, Yoon-Jung Choi, Sangjun Lee, Woojin Lim, Kyungsik Kim, Sohee Park, Jeong-Soo Im, Hong Gwan Seo, Kwang-Pil Ko, Sue K. Park; Received June 21, 2024 Accepted August 30, 2024 Published online November 28, 2024; DOI: https://doi.org/10.3803/EnM.2024.2071 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The increasing rate of excess body weight (EBW) in the global population has led to growing health concerns, including cancer-related EBW. We aimed to estimate the population attributable fraction (PAF) of cancer incidence and deaths linked to EBW in Korean individuals from 2015 to 2030 and to compare its value with various body mass index cutoffs.
Methods
Levin’s formula was used to calculate the PAF; the prevalence rates were computed using the Korean National Health and Nutrition Examination Survey data, while the relative risks of specific cancers related to EBW were estimated based on the results of Korean cohort studies. To account for the 15-year latency period when estimating the PAF in 2020, the prevalence rates from 2015 and attributable cases or deaths from 2020 were used.
Results
The PAF attributed to EBW was similar for both cancer incidence and deaths using either the World Health Organization (WHO) Asian-Pacific region standard or a modified Asian standard, with the WHO standard yielding the lowest values. In the Korean population, the PAFs of EBW for cancer incidence were 2.96% in men and 3.61% in women, while those for cancer deaths were 0.67% in men and 3.06% in women in 2020. Additionally, PAFs showed a gradual increase in both sexes until 2030.
Conclusion
The EBW continues to have a significant impact on cancer incidence and deaths in Korea. Effective prevention strategies targeting the reduction of this modifiable risk factor can substantially decrease the cancer burden.

Editorial

Reflections on Ending My Tenure as an Editor-in-Chief: Won-Young Lee; Received October 23, 2024 Accepted November 14, 2024 Published online November 27, 2024; DOI: https://doi.org/10.3803/EnM.2024.602 [Epub ahead of print]

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Brief Report

Metabolic Consequences of Glucagon-Like Peptide-1 Receptor Agonist Shortage: Deterioration of Glycemic Control in Type 2 Diabetes: Hun Jee Choe, Michael A. Nauck, Joon Ho Moon; Received August 19, 2024 Accepted October 7, 2024 Published online November 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.2150 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: In the context of a global shortage of glucagon-like peptide-1 (GLP-1) receptor agonists, we assessed the impact of discontinuing dulaglutide on metabolic control in individuals with type 2 diabetes. Our analysis included data from 69 individuals and revealed a significant deterioration in glycemic control following the discontinuation. Specifically, the average hemoglobin A1c level increased from 7.0%±0.9% to 8.1%±1.4% (P<0.001), and fasting glucose levels rose from 129±31 to 156±50 mg/dL (P<0.001) within 3 months after stopping the medication. Alternative treatments such as dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporter- 2 inhibitors were insufficient substitutes, highlighting the essential role of continuous GLP-1 receptor agonist therapy in maintaining metabolic health.

Original Article

Risk of Diabetes Mellitus in Adults with Intellectual Disabilities: A Nationwide Cohort Study: Hye Yeon Koo, In Young Cho, Yoo Jin Um, Yong-Moon Mark Park, Kyung Mee Kim, Chung Eun Lee, Kyungdo Han; Received July 31, 2024 Accepted October 15, 2024 Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2126 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations.
Methods
This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID.
Results
Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001).
Conclusion
Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.

Review Article

Brown Fat and Metabolic Health: The Diverse Functions of Dietary Components: Zachary Brown, Takeshi Yoneshiro; Received August 1, 2024 Accepted August 28, 2024 Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2121 [Epub ahead of print]

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Abstract PDF PubReader ePub: Brown and beige adipocytes utilize a variety of substrates for cold-induced thermogenesis, contributing to the clearance of metabolites in circulation and, consequently, metabolic health. Food-derived compounds that exhibit agonistic activity at temperature-sensitive transient receptor potential channels may serve as cold mimics to elicit thermogenesis and substrate utilization in brown adipose tissue (BAT). In addition to fatty acids and glucose, branched-chain amino acids (BCAAs), which are essential amino acids obtained from foods, are actively catabolized in BAT through mitochondrial BCAA carrier (MBC). The relative contribution of BCAAs to fueling the tricarboxylic acid cycle as a substrate (i.e., anaplerosis) is estimated to be relatively small, yet BCAA catabolism in BAT exerts a critical role in systemic insulin sensitivity. The nature of this apparent tension remained unclear until the recent discovery that active BCAA catabolism in BAT through MBC is critical for the synthesis of metabolites such as glutathione, which is delivered to the liver to improve hepatic insulin sensitivity through redox homeostasis. Novel mechanistic insights into the control of BAT function and systemic metabolism reveal the therapeutic potential of food-derived compounds for improving metabolic flexibility and insulin sensitivity.

Original Articles

Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice: Eun-Ok Lee, Hao Jin, Sungmin Kim, Hee Kyoung Joo, Yu Ran Lee, Soo Yeon An, Shuyu Piao, Kwon Ho Lee, Byeong Hwa Jeon; Received June 3, 2024 Accepted August 19, 2024 Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2061 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1^+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution.
Methods
APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1^+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes.
Results
APE1/Ref-1^+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1^+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1^+/- mice.
Conclusion
APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study: Kyoung Min Kim, Seol A Jang, Nam Ki Hong, Chul Sik Kim, Yumie Rhee, Seok Won Park, Steven R. Cummings, Gi Hyeon Seo; Received May 21, 2024 Accepted August 22, 2024 Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2047 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Inhibitory effects of denosumab on bone remodeling are reversible and disappear once treatment is discontinued. Herein, we examined whether and to what extent delayed denosumab administration is also associated with fracture risk using nation-wide data.
Methods
The study cohort included women aged 45 to 89 years who were started on denosumab for osteoporosis between October 2017 and December 2019 using data from the Korean Health Insurance Review and Assessment service. Participants were stratified according to the time of their subsequent denosumab administration from the last denosumab administration, including those with within 30 days early dosing (ED30), within the planned time of 180–210 days (referent), within 30–90 days of delayed dosing (DD90), within 90–180 days of delayed dosing (DD180), and longer than 181 days of delayed dosing (DD181+). The primary outcome was the incidence of all clinical fractures.
Results
A total of 149,199 participants included and 2,323 all clinical fractures (including 1,223 vertebral fractures) occurred. The incidence of all fractures was significantly higher in the DD90 compared to reference group (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.4). The risk of all fracture was even higher in the longer delayed DD180 group (HR, 1.9; 95% CI, 1.6 to 2.3) and DD181+ group (HR, 1.8; 95% CI, 1.5 to 2.2). Increased risks of fractures with delayed dosing were consistently observed for vertebral fractures.
Conclusion
Delayed denosumab dosing, even by 1 to 3 months, was significantly associated with increased fracture risk. Maintaining the correct dosing schedule should be emphasized when starting denosumab.

Corrigendum

Corrigendum: Correction of Figure. A Key Metabolic Regulator of Bone and Cartilage Health: Elizabeth Pérez-Hernández, Jesús Javier Pastrana-Carballo, Fernando Gómez-Chávez, Ramesh C. Gupta, Nury Pérez-Hernández; Published online November 19, 2024; DOI: https://doi.org/10.3803/EnM.2024.601 [Epub ahead of print]; Corrects: Endocrinol Metab 2022;37(4):559

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Original Articles

Genetic Landscape and Clinical Manifestations of Multiple Endocrine Neoplasia Type 1 in a Korean Cohort: A Multicenter Retrospective Analysis: Boram Kim, Seung Hun Lee, Chang Ho Ahn, Han Na Jang, Sung Im Cho, Jee-Soo Lee, Yu-Mi Lee, Su-Jin Kim, Tae-Yon Sung, Kyu Eun Lee, Woochang Lee, Jung-Min Koh, Moon-Woo Seong, Jung Hee Kim; Received April 9, 2024 Accepted July 24, 2024 Published online November 18, 2024; DOI: https://doi.org/10.3803/EnM.2024.2008 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants.
Methods
This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines.
Results
A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040).
Conclusion
The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

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; Received April 9, 2024 Accepted September 3, 2024 Published online November 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.2006 [Epub ahead of print]

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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.

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