1.Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea
Jung A KIM ; Kyeong Jin KIM ; Jimi CHOI ; Kyoung Jin KIM ; Eyun SONG ; Ji Hee YU ; Nam Hoon KIM ; Hye Jin YOO ; Ji A SEO ; Nan Hee KIM ; Kyung Mook CHOI ; Sei Hyun BAIK ; Sin Gon KIM
Endocrinology and Metabolism 2025;40(1):125-134
Background:
Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.
Methods:
We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.
Results:
Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.
Conclusion
ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.
2.Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization
Jung Hoon KIM ; Hye-Ok KIM ; Su-Yeon LEE ; Eun-A PARK ; Kyoung Hee CHOI ; Kiye KANG ; Eun Jeong YU ; Mi Kyoung KOONG ; Kyung-Ah LEE
Clinical and Experimental Reproductive Medicine 2025;52(1):44-55
Objective:
Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR.
Methods:
We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction.
Results:
KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients.
Conclusion
miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.
3.Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea
Jung A KIM ; Kyeong Jin KIM ; Jimi CHOI ; Kyoung Jin KIM ; Eyun SONG ; Ji Hee YU ; Nam Hoon KIM ; Hye Jin YOO ; Ji A SEO ; Nan Hee KIM ; Kyung Mook CHOI ; Sei Hyun BAIK ; Sin Gon KIM
Endocrinology and Metabolism 2025;40(1):125-134
Background:
Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.
Methods:
We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.
Results:
Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.
Conclusion
ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.
4.Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization
Jung Hoon KIM ; Hye-Ok KIM ; Su-Yeon LEE ; Eun-A PARK ; Kyoung Hee CHOI ; Kiye KANG ; Eun Jeong YU ; Mi Kyoung KOONG ; Kyung-Ah LEE
Clinical and Experimental Reproductive Medicine 2025;52(1):44-55
Objective:
Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR.
Methods:
We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction.
Results:
KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients.
Conclusion
miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.
5.Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea
Jung A KIM ; Kyeong Jin KIM ; Jimi CHOI ; Kyoung Jin KIM ; Eyun SONG ; Ji Hee YU ; Nam Hoon KIM ; Hye Jin YOO ; Ji A SEO ; Nan Hee KIM ; Kyung Mook CHOI ; Sei Hyun BAIK ; Sin Gon KIM
Endocrinology and Metabolism 2025;40(1):125-134
Background:
Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.
Methods:
We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.
Results:
Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.
Conclusion
ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.
6.Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization
Jung Hoon KIM ; Hye-Ok KIM ; Su-Yeon LEE ; Eun-A PARK ; Kyoung Hee CHOI ; Kiye KANG ; Eun Jeong YU ; Mi Kyoung KOONG ; Kyung-Ah LEE
Clinical and Experimental Reproductive Medicine 2025;52(1):44-55
Objective:
Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR.
Methods:
We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction.
Results:
KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients.
Conclusion
miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.
7.Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea
Jung A KIM ; Kyeong Jin KIM ; Jimi CHOI ; Kyoung Jin KIM ; Eyun SONG ; Ji Hee YU ; Nam Hoon KIM ; Hye Jin YOO ; Ji A SEO ; Nan Hee KIM ; Kyung Mook CHOI ; Sei Hyun BAIK ; Sin Gon KIM
Endocrinology and Metabolism 2025;40(1):125-134
Background:
Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.
Methods:
We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.
Results:
Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.
Conclusion
ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.
8.Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300–CD38 Axis
Ji-Hye SONG ; Hyo-Jin KIM ; Jangho LEE ; Seung-Pyo HONG ; Min-Yu CHUNG ; Yu-Geun LEE ; Jae Ho PARK ; Hyo-Kyoung CHOI ; Jin-Taek HWANG
Biomolecules & Therapeutics 2024;32(2):214-223
Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values.CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression.The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300–CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.
9.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
10.Folate intake in Korean adults:analysis of the 2016–2018 Korea National Health and Nutrition Examination Survey with newly established folate database
Eun-Ji PARK ; Inhwa HAN ; Kyoung Hye YU ; Sun Yung LY
Journal of Nutrition and Health 2024;57(4):418-434
Purpose:
The nutritional status of folate in Korean adults was evaluated using the newly established folate database (DB) and data from the 7th Korea National Health and Nutrition Examination Survey.
Methods:
This study analyzed the folate intake of 15,054 people (6,278 men and 8,776 women) and the relationship with serum folate concentration of 5,260 people (2,272 men and 2,988 women).
Results:
The average daily folate intake among Korean adults was lowest in the 19 to 29-year age group and highest in those in their 50s. Folate intake was higher in groups with higher education and household income, non-smokers, participants in aerobic physical activity, and dietary supplement users regardless of sex. Among men, office workers consumed more folate than physical workers. Vegetables and grains were the first and second most contributing food groups to folate intake. The serum folate levels were higher in women than men and lowest in the 19–29 year age group for both sexes. After adjusting for energy intake, age, income, smoking, physical activity, and dietary supplement intake, serum folate concentration increased significantly as intake increased (p < 0.001). The explanatory power (R2 ) of folate intake on the blood folate concentration was 0.183 and 0.141 in men and women, respectively.
Conclusion
The proportion of participants consuming less than the estimated average requirement was 48.1% and 65.3% in men and women, respectively. In particular, the folate intake and serum levels of young men aged 19–29 years were the lowest. Therefore, it is necessary to improve their folate nutritional status through a balanced diet. In addition, the newly established folate DB may be useful for evaluating the folate nutritional status of Koreans.

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