Endocrinology and Metabolism

Original Articles

Thyroid
Comparison of Ultrasensitive and Highly Sensitive Assay to Predict Stimulated Thyroglobulin Levels Using Unstimulated Levels in Differentiated Thyroid Cancer Patients: Jinsun Jang, Hyun Joo Kim, Seunggyun Ha, Kyong Yeun Jung, Gyeongseo Jung, Sun Wook Cho, Do Joon Park, Gi Jeong Cheon, Young Joo Park; Endocrinol Metab. 2025;40(5):759-771. Published online June 5, 2025; DOI: https://doi.org/10.3803/EnM.2025.2302

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Background
Thyroglobulin (Tg) measurement is an essential aspect of monitoring for differentiated thyroid cancer (DTC) patients. This study compared the performances of ultrasensitive Tg (ultraTg) and highly sensitive Tg (hsTg) assays in predicting stimulated Tg levels without thyroid-stimulating hormone stimulation.
Methods
Overall, 268 DTC patients who had undergone total thyroidectomy and either radioiodine treatment or I-123 diagnostic scanning were included. Unstimulated and stimulated Tg levels were measured using hsTg (BRAHMS Dynotest Tg-plus) and ultraTg (RIAKEY Tg immunoradiometric assay) assays. Correlations of each assay with the ability of unstimulated Tg levels to predict stimulated Tg ≥1 ng/mL were analyzed.
Results
hsTg and ultraTg showed a strong correlation (R=0.79, P<0.01); the correlation was weaker in Tg antibody-positive patients (R=0.52). UltraTg demonstrated higher sensitivity in predicting stimulated Tg ≥1 ng/mL compared with hsTg. The optimal cut-off for ultraTg was 0.12 ng/mL (sensitivity, 72.0%; specificity, 67.2%). hsTg at 0.105 ng/mL had lower sensitivity (39.8%) but higher specificity (91.5%). Eight discordant cases with low hsTg (<0.2 ng/mL) but elevated ultraTg (>0.23 ng/mL) were identified; three developed structural recurrence within 3.4 to 5.8 years. Two patients had an excellent response according to hsTg but an indeterminate or biochemical incomplete response according to ultraTg.
Conclusion
UltraTg demonstrated higher sensitivity in predicting positive stimulated Tg levels and potential recurrence compared with hsTg. However, its lower specificity may lead to more frequent classifications of biochemical incomplete response. UltraTg may be beneficial in clinically suspicious cases where hsTg falls below the cut-off, but its broader applicability requires further investigation.

Citations

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Unstimulated Highly Sensitive Thyroglobulin <0.2 ng/mL: Insufficient to Predict Stimulated Thyroglobulin <1 ng/mL?
Tae Yong Kim
Endocrinology and Metabolism.2025; 40(5): 687. CrossRef
Post-thyroidectomy ultrasonography versus thyroglobulin as a surveillance tool for locoregional recurrence in patients with differentiated thyroid carcinoma: A single centre 10-year study
Abhishek Mahajan, Vineeth Kurki, Pranjal Rai, Nilesh Sable, Ujjwal Agarwal, Richa Vaish, Nivedita Chakrabarty, Shreya Shukla, Anil D’Cruz, Prathamesh Pai, Kumar Prabhash, Vanita Noronha, Vijay Patil, Nandini Menon, Sarbani Ghosh Laskar, Asawari Patil, Mun
Frontiers in Endocrinology.2025;[Epub] CrossRef

Thyroid
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; Endocrinol Metab. 2025;40(2):236-246. Published online February 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2136

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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.

Citations

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Shared Decision-Making for Determining Treatment Strategies in Low-Risk Thyroid Cancer: Protocol of a Multicenter Cluster-Randomized Trial (MAeSTro-SDM)
Eun Kyung Lee, Min Joo Kim, Yul Hwangbo, Jae Hoon Moon, Sun Wook Cho, Young Jun Chai, June Young Choi, Yuh-Seog Jung, Kyu Eun Lee, Eun-Jae Chung, Kyungsik Kim, Su-jin Kim, Woochul Kim, Yoo Hyung Kim, Young Ki Lee, Jinsun Jang, Young Shin Song, Ka Hee Yi,
Journal of Korean Medical Science.2026;[Epub] CrossRef
Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP) (Endocrinol Metab 2025;40:236-46, Jae Hoon Moon et al.)
Eun Kyung Lee, Jae Hoon Moon, Young Joo Park
Endocrinology and Metabolism.2025; 40(4): 655. CrossRef
Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP) (Endocrinol Metab 2025;40:236-46, Jae Hoon Moon et al.)
Hoonsung Choi
Endocrinology and Metabolism.2025; 40(4): 653. CrossRef
Habitat imaging combined with multimodal analysis for preoperative risk stratification of papillary thyroid carcinoma
Jia-Wei Feng, You-Long Zhu, Lu Zhang, Yu-Xin Yang, An-Cheng Qin, Shui-Qing Liu, Yong Jiang
Insights into Imaging.2025;[Epub] CrossRef

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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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.

Citations

Citations to this article as recorded by

The impact of microscopic extrathyroidal extension on the prognosis of medullary thyroid carcinoma: A multicenter cohort study
Beyza Olcay Ozturk, Umran Keskin, Serhat Uysal, Aysa Hacioglu, Seda Karsli, Burak Andac, Umit Nur Ozbay, Hulyanur Sodan, Sebnem Burhan, Coskun Ates, Ugur Avci, Faruk Kilinc, Selvinaz Erol, Merve Catak, Zafer Pekkolay, Gulhan Akbaba, Goknur Yorulmaz, Sakin
Endocrinología, Diabetes y Nutrición.2025; 72(10): 501633. CrossRef
The impact of microscopic extrathyroidal extension on the prognosis of medullary thyroid carcinoma: A multicenter cohort study
Beyza Olcay Ozturk, Umran Keskin, Serhat Uysal, Aysa Hacioglu, Seda Karsli, Burak Andac, Umit Nur Ozbay, Hulyanur Sodan, Sebnem Burhan, Coskun Ates, Ugur Avci, Faruk Kilinc, Selvinaz Erol, Merve Catak, Zafer Pekkolay, Gulhan Akbaba, Goknur Yorulmaz, Sakin
Endocrinología, Diabetes y Nutrición (English ed.).2025; 72(10): 501633. CrossRef

Thyroid
Diagnostic Accuracy of Preoperative Radiologic Findings in Papillary Thyroid Microcarcinoma: Discrepancies with the Postoperative Pathologic Diagnosis and Implications for Clinical Outcomes: Ying Li, Seul Ki Kwon, Hoonsung Choi, Yoo Hyung Kim, Sunyoung Kang, Kyeong Cheon Jung, Jae-Kyung Won, Do Joon Park, Young Joo Park, Sun Wook Cho; Endocrinol Metab. 2024;39(3):450-460. Published online May 27, 2024; DOI: https://doi.org/10.3803/EnM.2023.1872

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Abstract PDF Supplementary Material PubReader ePub: Background
The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups.
Methods
In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings. Discrepancies between the preoperative and postoperative tumor sizes were analyzed, and clinical outcomes were assessed.
Results
The agreement rate between radiological and pathological tumor size was approximately 60%. Significant discrepancies were noted, including an increase in tumor size in 24.3% of cases. Notably, in 10.8% of patients, the postoperative tumor size exceeded 1 cm, despite being initially classified as 0.5 to 1.0 cm based on preoperative imaging. A postoperative tumor size >1 cm was associated with aggressive pathologic factors such as multiplicity, microscopic extrathyroidal extension, and LNM, as well as a higher risk of distant metastasis. In 30.1% of patients, LNM was diagnosed after surgery despite not being suspected before the procedure. This group was characterized by smaller metastatic foci and lower risks of distant metastasis or recurrence than patients with LNM detected both before and after surgery.
Conclusion
Among all risk groups of PTMCs, a subset showed an increase in tumor size, reaching 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis.

Editorial

Thyroid Thyroid Cancer Screening
To Screen or Not to Screen?: Do Joon Park; Endocrinol Metab. 2023;38(1):69-71. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.104

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Original Articles

Thyroid
Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves’ Disease: Min Joo Kim, Sun Wook Cho, Ye An Kim, Hoon Sung Choi, Young Joo Park, Do Joon Park, Bo Youn Cho; Endocrinol Metab. 2022;37(3):524-532. Published online June 16, 2022; DOI: https://doi.org/10.3803/EnM.2022.1418

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Background
Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves’ disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves’ disease.
Methods
Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy.
Results
The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months.
Conclusion
Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

Citations

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Outcomes of Fixed-Dose Radioactive Iodine Therapy in Hyperthyroidism and Optimization of Follow-Up After Treatment Failure With Low-Dose Antithyroid Medication
Panita Kantikool, Naphat Buraphanawibun
Cureus.2025;[Epub] CrossRef
Tingkat Keberhasilan Terapi Radioiodin Pertama pada Pasien Graves’ Disease
Aliya Khadijah Kemaleratu, Yuliana Rahmah Retnaningrum, Yudanti Riastiti
Jurnal Sains dan Kesehatan.2025; 6(1): 1. CrossRef
Association of high‐dose radioactive iodine therapy with PPM1D‐mutated clonal hematopoiesis in older individuals
Jaeryuk Kim, Sungwoo Bae, Jaeyong Choi, Sun‐Wha Im, Bukyoung Cha, Gyeongseo Jung, Sun Wook Cho, Eul‐Ju Seo, Young Ah Lee, Jin Chul Paeng, Young Joo Park, Jong‐Il Kim
Molecular Oncology.2025; 19(11): 3079. CrossRef
Characteristics of Japanese patients with Graves’ disease who fail first radioiodine therapy
Yuki Yamamoto, Hiroshi Fukazawa, Jun Ito, Kei Ito, Masanao Fujii, Aiko Hosoda, Yoshinori Osaki, Hiroaki Yagyu
Thyroid Science.2025; 2(4): 100028. CrossRef
Prospective study to evaluate radioactive iodine of 20 mCi vs 10–15 mCi in Graves’ disease
Wasit Kanokwongnuwat, Nawarat Penpong
BMC Endocrine Disorders.2024;[Epub] CrossRef
The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
Endocrinology and Metabolism.2023; 38(3): 338. CrossRef
Effect of liver dysfunction on outcome of radioactive iodine therapy for Graves’ disease
Yuyang Ze, Fei Shao, Xuefeng Feng, Shanmei Shen, Yan Bi, Dalong Zhu, Xiaowen Zhang
BMC Endocrine Disorders.2022;[Epub] CrossRef

Mineral, Bone & Muscle
Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study: Ye An Kim, Ji Won Yoon, Young Lee, Hyuk Jin Choi, Jae Won Yun, Eunsin Bae, Seung-Hyun Kwon, So Eun Ahn, Ah-Ra Do, Heejin Jin, Sungho Won, Do Joon Park, Chan Soo Shin, Je Hyun Seo; Endocrinol Metab. 2021;36(6):1189-1200. Published online December 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.1241

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Background
Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).
Methods
We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.
Results
rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.
Conclusion
The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Citations

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Prevalence and Progression of Vitamin D Deficiency in Greater Beirut and Mount Lebanon From 2013 to 2022: An Analysis of 19,452 Adults
Pia Chedid, Elie Salem‐Sokhn, Said El Shamieh, Rajaa Fakhoury
Journal of Clinical Laboratory Analysis.2025;[Epub] CrossRef
Genetic Variants Influencing Individual Vitamin D Status
Niel A. Karrow, Spencer E. Leuschner, Umesh K. Shandilya, Bonnie A. Mallard, Lauraine Wagter-Lesperance, Byram W. Bridle
Nutrients.2025; 17(16): 2673. CrossRef
Rare-Variant Genome-Wide Association and Polygenic Score Assessment of Vitamin D Status in a Middle Eastern Population
Nagham Nafiz Hendi, Umm-Kulthum Umlai, Omar Albagha, Georges Nemer
International Journal of Molecular Sciences.2025; 26(19): 9481. CrossRef
Implications of vitamin D deficiency in systemic inflammation and cardiovascular health
Sanjay Kumar Dey, Shashank Kumar, Diksha Rani, Shashank Kumar Maurya, Pratibha Banerjee, Madhur Verma, Sabyasachi Senapati
Critical Reviews in Food Science and Nutrition.2024; 64(28): 10438. CrossRef
Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization
Caroline De Souza Silverio , Carolina Bonilla
Biomédica.2024; 44(1): 45. CrossRef
Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women
Diana I. Aparicio-Bautista, Rogelio F. Jiménez-Ortega, Adriana Becerra-Cervera, Arnoldo Aquino-Gálvez, Valeria Ponce de León-Suárez, Leonora Casas-Ávila, Jorge Salmerón, Alberto Hidalgo-Bravo, Berenice Rivera-Paredez, Rafael Velázquez-Cruz
Frontiers in Endocrinology.2024;[Epub] CrossRef
Micronutrient-Associated Single Nucleotide Polymorphism and Mental Health: A Mendelian Randomization Study
Jingni Hui, Na Zhang, Meijuan Kang, Yifan Gou, Chen Liu, Ruixue Zhou, Ye Liu, Bingyi Wang, Panxing Shi, Shiqiang Cheng, Xuena Yang, Chuyu Pan, Feng Zhang
Nutrients.2024; 16(13): 2042. CrossRef
Associations between Disc Hemorrhage and Primary Open-Angle Glaucoma Based on Genome-Wide Association and Mendelian Randomization Analyses
Je Hyun Seo, Young Lee, Hyuk Jin Choi
Biomedicines.2024; 12(10): 2253. CrossRef
Association between Vitamin D Deficiency and Clinical Parameters in Men and Women Aged 50 Years or Older: A Cross-Sectional Cohort Study
Ji Hyun Lee, Ye An Kim, Young Sik Kim, Young Lee, Je Hyun Seo
Nutrients.2023; 15(13): 3043. CrossRef
Single nucleotide polymorphisms in vitamin D binding protein and 25-hydroxylase genes affect vitamin D levels in adolescents of Arab ethnicity in Kuwait
Abdur Rahman, Mohamed Abu-Farha, Arshad Channanath, Maha M. Hammad, Emil Anoop, Betty Chandy, Motasem Melhem, Fahd Al-Mulla, Thangavel Alphonse Thanaraj, Jehad Abubaker
Frontiers in Endocrinology.2023;[Epub] CrossRef
Recent Information on Vitamin D Deficiency in an Adult Korean Population Visiting Local Clinics and Hospitals
Rihwa Choi, Sung-Eun Cho, Sang Gon Lee, Eun Hee Lee
Nutrients.2022; 14(9): 1978. CrossRef
The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies
Massimiliano Berretta, Vincenzo Quagliariello, Alessia Bignucolo, Sergio Facchini, Nicola Maurea, Raffaele Di Francia, Francesco Fiorica, Saman Sharifi, Silvia Bressan, Sara N. Richter, Valentina Camozzi, Luca Rinaldi, Carla Scaroni, Monica Montopoli
Antioxidants.2022; 11(6): 1090. CrossRef
A Genome-Wide Association Study of Genetic Variants of Apolipoprotein A1 Levels and Their Association with Vitamin D in Korean Cohorts
Young Lee, Ji Won Yoon, Ye An Kim, Hyuk Jin Choi, Byung Woo Yoon, Je Hyun Seo
Genes.2022; 13(9): 1553. CrossRef
Genetic Determinants of 25-Hydroxyvitamin D Concentrations and Their Relevance to Public Health
Elina Hyppönen, Karani S. Vimaleswaran, Ang Zhou
Nutrients.2022; 14(20): 4408. CrossRef
On the Centennial of Vitamin D—Vitamin D, Inflammation, and Autoimmune Thyroiditis: A Web of Links and Implications
Leonidas H. Duntas, Krystallenia I. Alexandraki
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The genetic and epigenetic contributions to the development of nutritional rickets
Innocent Ogunmwonyi, Adewale Adebajo, Jeremy Mark Wilkinson
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Thyroid
Comparison of Korean vs. American Thyroid Imaging Reporting and Data System in Malignancy Risk Assessment of Indeterminate Thyroid Nodules: Sunyoung Kang, Seul Ki Kwon, Hoon Sung Choi, Min Joo Kim, Young Joo Park, Do Joon Park, Sun Wook Cho; Endocrinol Metab. 2021;36(5):1111-1120. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1208

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Background
The management of cytologically indeterminate thyroid nodules is challenging for clinicians. This study aimed to compare the diagnostic performance of the Korean Thyroid Imaging Reporting and Data Systems (K-TIRADS) with that of the American College of Radiology (ACR)-TIRADS for predicting the malignancy risk of indeterminate thyroid nodules.
Methods
Thyroid nodules diagnosed by fine-needle aspiration (FNA) followed by surgery or core needle biopsy at a single referral hospital were enrolled.
Results
Among 200 thyroid nodules, 78 (39.0%) nodules were classified as indeterminate by FNA (Bethesda category III, IV, and V), and 114 (57.0%) nodules were finally diagnosed as malignancy by surgery or core needle biopsy. The area under the curve (AUC) was higher for FNA than for either TIRADS system in all nodules, while all three methods showed similar AUCs for indeterminate nodules. However, for Bethesda category III nodules, applying K-TIRADS 5 significantly increased the risk of malignancy compared to a cytological examination alone (50.0% vs. 26.5%, P=0.028), whereas applying ACR-TIRADS did not lead to a change.
Conclusion
K-TIRADS and ACR-TIRADS showed similar diagnostic performance in assessing indeterminate thyroid nodules, and K-TIRADS had beneficial effects for malignancy prediction in Bethesda category III nodules.

Citations

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Is the nodule location a predictive risk factor for cancer in AUS/FLUS thyroid nodules? A retrospective cohort study
Saad M. Alqahtani, Bassam A. Altalhi, Yousef S. Alalawi, Saif S. Al-Sobhi
Asian Journal of Surgery.2024; 47(6): 2574. CrossRef
Correlation between Ultrasound TI-RADS and Bethesda FNAC Scoring in Thyroid Lesions: A Retrospective Analysis
Smriti Mathur, Amit Chail, Amit K. Das, Seerat Pal, Ranjit S. Lahel
Medical Journal of Dr. D.Y. Patil Vidyapeeth.2024; 17(3): 533. CrossRef
Diagnostic Performance of Various Ultrasound Risk Stratification Systems for Benign and Malignant Thyroid Nodules: A Meta-Analysis
Ji-Sun Kim, Byung Guk Kim, Gulnaz Stybayeva, Se Hwan Hwang
Cancers.2023; 15(2): 424. CrossRef
The impact of thyroid imaging reporting and data system on the management of Bethesda III thyroid nodules
Saad M. Alqahtani, Saif S. Al-Sobhi, Mohammed A. Alturiqy, Riyadh I. Alsalloum, Hindi N. Al-Hindi
Journal of Taibah University Medical Sciences.2023; 18(3): 506. CrossRef
Diagnostic Performance of Six Ultrasound Risk Stratification Systems for Thyroid Nodules: A Systematic Review and Network Meta-Analysis
Do Hyun Kim, Sung Won Kim, Mohammed Abdullah Basurrah, Jueun Lee, Se Hwan Hwang
American Journal of Roentgenology.2023; 220(6): 791. CrossRef
Diagnostic efficiency among Eu-/C-/ACR-TIRADS and S-Detect for thyroid nodules: a systematic review and network meta-analysis
Longtao Yang, Cong Li, Zhe Chen, Shaqi He, Zhiyuan Wang, Jun Liu
Frontiers in Endocrinology.2023;[Epub] CrossRef
Comparison of diagnostic performance of two ultrasound risk stratification systems for thyroid nodules: a systematic review and meta-analysis
Yun Jin Kang, Hee Sun Ahn, Gulnaz Stybayeva, Ju Eun Lee, Se Hwan Hwang
La radiologia medica.2023; 128(11): 1407. CrossRef
Diagnostic Performance of ACR and Kwak TI-RADS for Benign and Malignant Thyroid Nodules: An Update Systematic Review and Meta-Analysis
Yun Jin Kang, Gulnaz Stybayeya, Ju Eun Lee, Se Hwan Hwang
Cancers.2022; 14(23): 5961. CrossRef
Comparison of Thyroid Imaging Reporting and Data Systems in Malignancy Risk Stratification of Indeterminate Thyroid Nodules
Bo Hyun Kim
Endocrinology and Metabolism.2021; 36(5): 974. CrossRef

Clinical Study
A Phase II Multi-Center, Non-Randomized, Parallel Group, Non-Inferiority Study to Compare the Efficacy of No Radioactive Iodine Remnant Ablation to Remnant Ablation Treatment in Low- to Intermediate-Risk of Papillary Thyroid Cancer: The MOREthyroid Trial Protocol: Eun Kyung Lee, You Jin Lee, Young Joo Park, Jae Hoon Moon, Ka Hee Yi, Koon Soon Kim, Joo Hee Lee, Sun Wook Cho, Jungnam Joo, Yul Hwangbo, Sujeong Go, Do Joon Park; Endocrinol Metab. 2020;35(3):571-577. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.681

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Background
Radioactive iodine (RAI) remnant ablation is recommended in patients with papillary thyroid cancer (PTC) and extrathyroidal extension or central lymph node metastasis. However, there exists little evidence about the necessity of remnant ablation in PTC patients with low- to intermediate-risk, those have been increasing in recent decades.
Methods
This multicenter, prospective, non-randomized, parallel group clinical trial will enroll 310 eligible patients with low- to intermediate-risk of thyroid cancer. Inclusion criteria are patients who recently underwent total thyroidectomy for PTC with 3 or less tumors of size 1≤ to ≤2 cm with no microscopic extension and N0/x, or size ≤2 cm with microscopic extension and/or N1a (number of lymph node ≤3, size of tumor foci ≤0.2 cm, and lymph node ratio <0.4). Patients choose to undergo RAI ablation (¹³¹I, dose 1.1 GBq) or diagnostic whole-body scan (DxWBS) (¹³¹I or ¹²³I, dose 0.074 to 0.222 GBq), followed by subsequent measurement of stimulated thyroglobulin (sTg) within 1 year. Survey for quality of life (QOL) will be performed at baseline and at 1 year after follow-up. The total enrollment period is 5 years, and patients will be followed up for 1 year. The primary endpoint is the non-inferiority of surgery alone to surgery with ablation in terms of biochemical remission (BCR) rate (sTg ≤2 ng/mL) without evidence of structural recurrence. The secondary endpoint was the difference of QOL.
Conclusion
This study will evaluate whether surgery alone achieves similar BCR and improved QOL compared to RAI ablation in patients with low- to intermediate-risk PTC within 1 year.

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Radioactive Iodine Therapy in Differentiated Thyroid Cancer: Summary of the Korean Thyroid Association Guidelines 2024 from Nuclear Medicine Perspective, Part-II
So Won Oh, Sohyun Park, Ari Chong, Keunyoung Kim, Ji-In Bang, Youngduk Seo, Chae Moon Hong, Sang-Woo Lee
Nuclear Medicine and Molecular Imaging.2025; 59(1): 8. CrossRef
Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 6. Radioactive Iodine Treatment after Thyroidectomy 2024
Sohyun Park, Ari Chong, Ho-Cheol Kang, Keunyoung Kim, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Ji-In Bang, Youngduk Seo, Young Shin Song, So Won Oh, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Chae Moon Hong, Sang-Woo Lee
International Journal of Thyroidology.2024; 17(1): 97. CrossRef

Clinical Study
Postoperative Thyroid-Stimulating Hormone Levels Did Not Affect Recurrence after Thyroid Lobectomy in Patients with Papillary Thyroid Cancer: Myung-Chul Lee, Min Joo Kim, Hoon Sung Choi, Sun Wook Cho, Guk Haeng Lee, Young Joo Park, Do Joon Park; Endocrinol Metab. 2019;34(2):150-157. Published online May 10, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.150

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Background

Thyroid-stimulating hormone (TSH) suppression is recommended for patients who undergo thyroidectomy for differentiated thyroid cancer (DTC). However, the impact of TSH suppression on clinical outcomes in low-risk DTC remains uncertain. Therefore, we investigated the effects of postoperative TSH levels on recurrence in patients with low-risk DTC after thyroid lobectomy.

Methods

Patients (n=1,528) who underwent thyroid lobectomy for papillary thyroid carcinoma between 2000 and 2012 were included in this study. According to the mean and dominant TSH values during the entire follow-up period or 5 years, patients were divided into four groups (<0.5, 0.5 to 1.9, 2.0 to 4.4, and ≥4.5 mIU/L). Recurrence-free survival was compared among the groups.

Results

During the 5.6 years of follow-up, 21 patients (1.4%) experienced recurrence. Mean TSH levels were within the recommended low-normal range (0.5 to 1.9 mIU/L) during the total follow-up period or 5 years in 38.1% or 36.0% of patients. The mean and dominant TSH values did not affect recurrence-free survival. Adjustment for other risk factors did not alter the results.

Conclusion

Serum TSH levels did not affect short-term recurrence in patients with low-risk DTC after thyroid lobectomy. TSH suppression should be conducted more selectively.

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Corrigendum

Miscellaneous
Corrigendum: Author's Name Correction. Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro): Jae Hoon Moon, Ji-hoon Kim, Eun Kyung Lee, Kyu Eun Lee, Sung Hye Kong, Yeo Koon Kim, Woo-Jin Jeong, Chang Yoon Lee, Roh-Eul Yoo, Yul Hwangbo, Young Shin Song, Min Joo Kim, Sun Wook Cho, Su-jin Kim, Eun-Jae Chung, June Young Choi, Chang Hwan Ryu, You Jin Lee, Jeong Hun Hah, Yuh-Seog Jung, Junsun Ryu, Yunji Hwang, Sue K. Park, Ho Kyung Sung, Ka Hee Yi, Do Joon Park, Young Joo Park; Endocrinol Metab. 2018;33(3):427. Published online August 14, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.427

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Original Articles

Thyroid
Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro): Jae Hoon Moon, Ji-hoon Kim, Eun Kyung Lee, Kyu Eun Lee, Sung Hye Kong, Yeo Koon Kim, Woo-jin Jung, Chang Yoon Lee, Roh-Eul Yoo, Yul Hwangbo, Young Shin Song, Min Joo Kim, Sun Wook Cho, Su-jin Kim, Eun Jae Jung, June Young Choi, Chang Hwan Ryu, You Jin Lee, Jeong Hun Hah, Yuh-Seog Jung, Junsun Ryu, Yunji Hwang, Sue K. Park, Ho Kyung Sung, Ka Hee Yi, Do Joon Park, Young Joo Park; Endocrinol Metab. 2018;33(2):278-286. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.278

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Background

The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups.

Methods

This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis.

Results

Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014).

Conclusion

The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.

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Multifocality and Progression of Papillary Thyroid Microcarcinoma During Active Surveillance
Ryuta Nagaoka, Aya Ebina, Kazuhisa Toda, Tomoo Jikuzono, Marie Saitou, Masaomi Sen, Hiroko Kazusaka, Mami Matsui, Keiko Yamada, Hiroki Mitani, Iwao Sugitani
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Active Surveillance as an Effective Management Option for Low-Risk Papillary Thyroid Microcarcinoma
Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
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The Concept of Economic Evaluation and Its Application in Thyroid Cancer Research
Kyungsik Kim, Mijin Kim, Woojin Lim, Bo Hyun Kim, Sue K. Park
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Genomic and Transcriptomic Characteristics According to Size of Papillary Thyroid Microcarcinoma
Young Shin Song, Byung-Hee Kang, Seungbok Lee, Seong-Keun Yoo, Young Sik Choi, Jungsun Park, Dong Yoon Park, Kyu Eun Lee, Jeong-Sun Seo, Young Joo Park
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Experience with Active Surveillance of Thyroid Low-Risk Carcinoma in a Developing Country
Alvaro Sanabria
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Association of Patient Age With Progression of Low-risk Papillary Thyroid Carcinoma Under Active Surveillance
Alexandra Koshkina, Rouhi Fazelzad, Iwao Sugitani, Akira Miyauchi, Lehana Thabane, David P. Goldstein, Sangeet Ghai, Anna M. Sawka
JAMA Otolaryngology–Head & Neck Surgery.2020; 146(6): 552. CrossRef
Active surveillance in low risk papillary thyroid carcinoma
Fabian Pitoia, Anabella Smulever
World Journal of Clinical Oncology.2020; 11(6): 320. CrossRef
Early Diagnosis of Low-Risk Papillary Thyroid Cancer Results Rather in Overtreatment Than a Better Survival
Jolanta Krajewska, Aleksandra Kukulska, Malgorzata Oczko-Wojciechowska, Agnieszka Kotecka-Blicharz, Katarzyna Drosik-Rutowicz, Malgorzata Haras-Gil, Barbara Jarzab, Daria Handkiewicz-Junak
Frontiers in Endocrinology.2020;[Epub] CrossRef
The dilemma of papillary thyroid microcarcinoma management. To operate or not to operate, that is the question
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Computed Tomography for Detecting Cervical Lymph Node Metastasis in Patients Who Have Papillary Thyroid Microcarcinoma with Tumor Characteristics Appropriate for Active Surveillance
Dong-Hwa Lee, Yeo Koon Kim, Hyeong Won Yu, June Young Choi, So Yeon Park, Jae Hoon Moon
Thyroid.2019; 29(11): 1653. CrossRef
The dilemma of papillary thyroid microcarcinoma management. To operate or not to operate, that is the question
Juan C Galofré
Endocrinología, Diabetes y Nutrición (English ed.).2019; 66(8): 469. CrossRef
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Ultrasound-guided percutaneous laser ablation for papillary thyroid microcarcinoma: a retrospective analysis of 37 patients
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Evolving management considerations in active surveillance for micropapillary thyroid carcinoma
Allen S. Ho, Irene Chen, Michelle Melany, Wendy L. Sacks
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Thyroid
Star-Shaped Intense Uptake of ¹³¹I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq: Sung Hye Kong, Jung Ah Lim, Young Shin Song, Shinje Moon, Ye An Kim, Min Joo Kim, Sun Wook Cho, Jae Hoon Moon, Ka Hee Yi, Do Joon Park, Bo Youn Cho, Young Joo Park; Endocrinol Metab. 2018;33(2):228-235. Published online May 4, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.228

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Background

After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of ¹³¹I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis.

Methods

Total 636 patients who received ¹³¹I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS.

Results

In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts.

Conclusion

Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

Citations

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Prognostic value of star-shaped intense uptake of 131I in thyroid cancer patients
Liu Xiao, Wen Jie Zhang, Yue Qi Wang, Lin Li
Revista Española de Medicina Nuclear e Imagen Molecular (English Edition).2021; 40(1): 30. CrossRef
Valores pronósticos de la captación en estrella de 131I en pacientes con cáncer diferenciado de tiroides
L. Xiao, W.J. Zhang, Y.Q. Wang, L. Li
Revista Española de Medicina Nuclear e Imagen Molecular.2021; 40(1): 30. CrossRef
Comparison between planar and single-photon computed tomography images for radiation intensity quantification in iodine-131 scintigraphy
Yusuke Iizuka, Tomohiro Katagiri, Minoru Inoue, Kiyonao Nakamura, Takashi Mizowaki
Scientific Reports.2021;[Epub] CrossRef

Thyroid
Validity and Reliability of the Korean Version of the Hyperthyroidism Symptom Scale: Jie-Eun Lee, Dong Hwa Lee, Tae Jung Oh, Kyoung Min Kim, Sung Hee Choi, Soo Lim, Young Joo Park, Do Joon Park, Hak Chul Jang, Jae Hoon Moon; Endocrinol Metab. 2018;33(1):70-78. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.70

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Background

Thyrotoxicosis is a common disease resulting from an excess of thyroid hormones, which affects many organ systems. The clinical symptoms and signs are relatively nonspecific and can vary depending on age, sex, comorbidities, and the duration and cause of the disease. Several symptom rating scales have been developed in an attempt to assess these symptoms objectively and have been applied to diagnosis or to evaluation of the response to treatment. The aim of this study was to assess the reliability and validity of the Korean version of the hyperthyroidism symptom scale (K-HSS).

Methods

Twenty-eight thyrotoxic patients and 10 healthy subjects completed the K-HSS at baseline and after follow-up at Seoul National University Bundang Hospital. The correlation between K-HSS scores and thyroid function was analyzed. K-HSS scores were compared between baseline and follow-up in patient and control groups. Cronbach's α coefficient was calculated to demonstrate the internal consistency of K-HSS.

Results

The mean age of the participants was 34.7±9.8 years and 13 (34.2%) were men. K-HSS scores demonstrated a significant positive correlation with serum free thyroxine concentration and decreased significantly with improved thyroid function. K-HSS scores were highest in subclinically thyrotoxic subjects, lower in patients who were euthyroid after treatment, and lowest in the control group at follow-up, but these differences were not significant. Cronbach's α coefficient for the K-HSS was 0.86.

Conclusion

The K-HSS is a reliable and valid instrument for evaluating symptoms of thyrotoxicosis in Korean patients.

Citations

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Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients (MASTER study)
Ja Kyung Lee, Eu Jeong Ku, Su-jin Kim, Woochul Kim, Jae Won Cho, Kyong Yeun Jung, Hyeong Won Yu, Yea Eun Kang, Mijin Kim, Hee Kyung Kim, Junsun Ryu, June Young Choi
Annals of Surgical Treatment and Research.2024; 106(1): 19. CrossRef
Effect of increased levothyroxine dose on depressive mood in older adults undergoing thyroid hormone replacement therapy
Jae Hoon Moon, Ji Won Han, Tae Jung Oh, Sung Hee Choi, Soo Lim, Ki Woong Kim, Hak Chul Jang
Clinical Endocrinology.2020; 93(2): 196. CrossRef
Clinical Feasibility of Monitoring Resting Heart Rate Using a Wearable Activity Tracker in Patients With Thyrotoxicosis: Prospective Longitudinal Observational Study
Jie-Eun Lee, Dong Hwa Lee, Tae Jung Oh, Kyoung Min Kim, Sung Hee Choi, Soo Lim, Young Joo Park, Do Joon Park, Hak Chul Jang, Jae Hoon Moon
JMIR mHealth and uHealth.2018; 6(7): e159. CrossRef

Endocrine Research
Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1: Hwa Young Ahn, Hwan Hee Kim, Ye An Kim, Min Kim, Jung Hun Ohn, Sung Soo Chung, Yoon-Kwang Lee, Do Joon Park, Kyong Soo Park, David D. Moore, Young Joo Park; Endocrinol Metab. 2015;30(4):584-592. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.584

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Background

Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1).

Methods

We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line

Results

Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.

Conclusion

We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

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Safety and efficacy of resmetirom in metabolic dysfunction-associated steatohepatitis (MASH): a systematic review and meta-analysis
Laraib Abbasi, Qunoot Irfan, Syed Muhammad Mehdi Zaidi, Izma Jawed, Abdullah Malik, Shamama Kaleem
European Journal of Gastroenterology & Hepatology.2025; 37(4): 395. CrossRef
Metabolic Dysfunction–Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options
Piero Portincasa, Mohamad Khalil, Laura Mahdi, Valeria Perniola, Valeria Idone, Annarita Graziani, Gyorgy Baffy, Agostino Di Ciaula
International Journal of Molecular Sciences.2024; 25(11): 5640. CrossRef
Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease
Ting-ying Jiao, Yuan-di Ma, Xiao-zhen Guo, Yun-fei Ye, Cen Xie
Acta Pharmacologica Sinica.2022; 43(5): 1103. CrossRef
Loperamide induces excessive accumulation of bile acids in the liver of mice with different diets
Zili Lei, Hedong Rong, Yanhong Yang, Siping Yu, Tianle Zhang, Lei Chen, Ya Nie, Qi Song, Qing Hu, Jiao Guo
Toxicology.2022; 477: 153278. CrossRef
Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Giuseppe Ferrandino, Rachel R. Kaspari, Olga Spadaro, Andrea Reyna-Neyra, Rachel J. Perry, Rebecca Cardone, Richard G. Kibbey, Gerald I. Shulman, Vishwa Deep Dixit, Nancy Carrasco
Proceedings of the National Academy of Sciences.2017;[Epub] CrossRef

Thyroid
The Frequency and Clinical Implications of the BRAF^V600E Mutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades: A Ram Hong, Jung Ah Lim, Tae Hyuk Kim, Hoon Sung Choi, Won Sang Yoo, Hye Sook Min, Jae Kyung Won, Kyu Eun Lee, Kyeong Cheon Jung, Do Joon Park, Young Joo Park; Endocrinol Metab. 2014;29(4):505-513. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.505

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Background

Over the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAF^V600E, which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAF^V600E mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed.

Methods

The present study included 2,624 patients who underwent a thyroidectomy for PTC during two preselected periods; 1995 to 2003 and 2009 to 2012. The BRAF^V600E mutation status of each patient was confirmed using the polymerase chain reaction-restriction fragment length polymorphism method or by the direct sequencing of DNA.

Results

The prevalence of the BRAF^V600E mutation in Korean PTC patients increased from 62.2% to 73.7% (P=0.001) over the last two decades. Additionally, there was a greater degree of extrathyroidal extension (ETE) and lymph node metastasis in 2009 to 2012 patients with the BRAF^V600E mutation and a higher frequency of thyroiditis and follicular variant-PTC in 2009 to 2012 patients with wild-type BRAF. However, only the frequency of ETE was significantly higher in 1995 to 2003 patients with the BRAF^V600E mutation (P=0.047). Long-term recurrence rates during a 10-year median follow-up did not differ based on BRAF^V600E mutation status.

Conclusion

The BRAF^V600E mutation rate in Korean PTC patients has been persistently high (approximately 70%) over the past two decades and continues to increase. The present findings demonstrate that BRAF^V600E-positive PTC was associated with more aggressive clinicopathological features, especially in patients who were recently diagnosed, suggesting that BRAF^V600E mutation status may be a useful prognostic factor for PTC in patients recently diagnosed with this disease.

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Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients
Young Shin Song, Jung Ah Lim, Hoonsung Choi, Jae‐Kyung Won, Jae Hoon Moon, Sun Wook Cho, Kyu Eun Lee, Young Joo Park, Ka Hee Yi, Do Joon Park, Jeong‐Sun Seo
Cancer.2016; 122(9): 1370. CrossRef
Prognostic Significance of TERT Promoter Mutations in Papillary Thyroid Carcinomas in a BRAFV600E Mutation–Prevalent Population
Seung Eun Lee, Tae Sook Hwang, Yoon-La Choi, Hye Seung Han, Wan Seop Kim, Min Hye Jang, Suk Kyeong Kim, Jung Hyun Yang
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Young Shin Song, Jung Ah Lim, Young Joo Park
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Tae Sook Hwang
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Negative Expression of CPSF2 Predicts a Poorer Clinical Outcome in Patients with Papillary Thyroid Carcinoma
Tae Yon Sung, Mijin Kim, Tae Yong Kim, Won Gu Kim, Yangsoon Park, Dong Eun Song, Su-Yeon Park, Hyemi Kwon, Yun Mi Choi, Eun Kyung Jang, Min Ji Jeon, Young Kee Shong, Suck Joon Hong, Won Bae Kim
Thyroid.2015; 25(9): 1020. CrossRef

Thyroid
The Expression of Tumor-Associated Macrophages in Papillary Thyroid Carcinoma: Seunghwan Kim, Sun Wook Cho, Hye Sook Min, Kang Min Kim, Gye Jeong Yeom, Eun Young Kim, Kyu Eun Lee, Yeo Gyu Yun, Do Joon Park, Young Joo Park; Endocrinol Metab. 2013;28(3):192-198. Published online September 13, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.3.192

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Background

Tumor-associated macrophages (TAMs) play a tumorigenic role related to advanced staging and poor prognosis in many human cancers including thyroid cancers. Yet, a functional role of TAMs in papillary thyroid carcinoma (PTC) has not been established. The aim of this study was to investigate TAM expression in human PTC with lymph node (LN) metastasis.

Methods

Thirty-six patients who underwent surgery after being diagnosed with PTC with LN metastasis were included. Primary tumor tissues were immunohistochemically stained with an anti-CD68 antibody and clinical characteristics according to TAM density were evaluated.

Results

The TAM densities (CD68⁺ cells) varied from 5% to 70%, in all tumor areas, while few cells were stained in adjacent normal tissues. TAMs were identified as CD68⁺ cells with thin, elongated cytoplasmic extensions that formed a canopy structure over tumor cells. Comparing clinicopathologic characteristics between tumors with low (<25%) and high (25% to 70%) TAM densities, primary tumors were larger in the high density group than in the low density group (2.0±0.1 vs. 1.5±0.1; P=0.009).

Conclusion

TAMs were identified in primary PTC tumors with LN metastasis and higher TAM densities were related to larger tumor sizes, suggesting a tumorigenic role of TAMs in human PTCs.

Citations

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Thyroid
Expression of Thyroid Stimulating Hormone Receptor mRNA in Mouse C2C12 Skeletal Muscle Cells: Jung Hun Ohn, Sun Kyoung Han, Do Joon Park, Kyong Soo Park, Young Joo Park; Endocrinol Metab. 2013;28(2):119-124. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.119

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Abstract PDF PubReader

Background

We analyzed whether thyroid stimulating hormone receptor (TSH-R) is expressed in a skeletal muscle cell line and if TSH has influence on the differentiation of muscle cells or on the determination of muscle fiber types.

Methods

TSH-R gene expression was detected with nested real-time polymerase chain reaction (RT-PCR) in C2C12, a mouse skeletal muscle cell line. The effect of TSH on myotube differentiation was assessed by microscopic examination of myotube formation and through the measurement of expression of muscle differentiation markers, i.e., myogenin and myoD, and muscle type-specific genes, i.e., MyHC1, MyHC2a, and MyHC2b, with quantitative RT-PCR before and after incubation of C2C12 myotube with TSH.

Results

TSH-R was expressed in the mouse skeletal muscle cell line. However, treatment with TSH had little effect on the differentiation of muscle cells, although the expression of the muscle differention marker myogenin was significantly increased after TSH treatment. Treatment of TSH did not affect the expression of muscle type-specific genes.

Conclusion

TSH-R is expressed in a mouse skeletal muscle cell line, but the role of TSH receptor signaling in skeletal muscle needs further investigation.

Citations

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Associations between thyroid hormones and appendicular skeletal muscle index, and hand grip strength in people with diabetes: The KAMOGAWA-A study
Shinnosuke Hata, Hiroshi Okada, Megumi Minamida, Junya Hironaka, Yuka Hasegawa, Yuriko Kondo, Hanako Nakajima, Nobuko Kitagawa, Takuro Okamura, Yoshitaka Hashimoto, Takafumi Osaka, Noriyuki Kitagawa, Saori Majima, Takafumi Senmaru, Emi Ushigome, Naoko Nak
Diabetes Research and Clinical Practice.2024; 209: 111573. CrossRef
Clinical parameters correlated with the psoas muscle index in Japanese individuals with type 2 diabetes mellitus
Emi Asano-Hayami, Yoshiaki Morishita, Tomohide Hayami, Yuka Shibata, Toshiki Kiyose, Sachiko Sasajima, Yusuke Hayashi, Mikio Motegi, Makoto Kato, Saeko Asano, Hiromi Nakai-Shimoda, Yuichiro Yamada, Emiri Miura-Yura, Tatsuhito Himeno, Masaki Kondo, Shin Ts
Diabetology International.2023; 14(1): 76. CrossRef
Effect of Thyroid-Stimulating Hormone Suppression on Muscle Function After Total Thyroidectomy in Patients With Thyroid Cancer
Jun Choul Lee, Byong-Sop Song, Young Mi Kang, Yu-Ri Kim, Yea Eun Kang, Ju Hee Lee, Minho Shong, Hyon-Seung Yi
Frontiers in Endocrinology.2021;[Epub] CrossRef
Different Relationships Between Thyrotropin and Muscle Strength According to Sex and Age in Euthyroid Koreans (The 6th Korea National Health and Nutritional Examination Survey 2014–2015)
Seong Hee Ahn, Da Hea Seo, Yongin Cho, Mihye Jung, So Hun Kim, Seongbin Hong
Thyroid.2020; 30(12): 1710. CrossRef
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Jeongmin Lee, Kwanhoon Jo, Jeonghoon Ha, Dong-Jun Lim, Jung Min Lee, Sang-Ah Chang, Moo Il Kang, Min-Hee Kim, Flavia Magri
International Journal of Endocrinology.2020; 2020: 1. CrossRef
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Hui Tang, Shuai Deng, Jian-guang Cai, Xue-nan Ma, Man Liu, Liang Zhou
International Journal of Diabetes in Developing Countries.2019; 39(3): 486. CrossRef
Thyroid Function as a Predictor of Handgrip Strength Among Middle-Aged and Older Euthyroid Adults: The TCLSIH Cohort Study
Yeqing Gu, Ge Meng, Hongmei Wu, Qing Zhang, Li Liu, Xue Bao, Yawen Wang, Shunming Zhang, Shaomei Sun, Xing Wang, Ming Zhou, Qiyu Jia, Kun Song, Kaijun Niu
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Association of Serum TSH With Handgrip Strength in Community-Dwelling Euthyroid Elderly
Beom-Jun Kim, Seung Hun Lee, Carlos M Isales, Mark W Hamrick, Mi Kyung Kwak, Jung-Min Koh
The Journal of Clinical Endocrinology & Metabolism.2018; 103(11): 3986. CrossRef
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Grigorios Panagiotou, Kalliopi Pazaitou-Panayiotou, Stavroula A. Paschou, Despina Komninou, Nikolaos Kalogeris, Andromachi Vryonidou, Christos S. Mantzoros
Thyroid.2016; 26(8): 1039. CrossRef
Thyroid-stimulating hormone improves insulin sensitivity in skeletal muscle cells via cAMP/PKA/CREB pathway-dependent upregulation of insulin receptor substrate-1 expression
Min Kyong Moon, Geun Hyung Kang, Hwan Hee Kim, Sun Kyoung Han, Young Do Koo, Sun Wook Cho, Ye An Kim, Byung-Chul Oh, Do Joon Park, Sung Soo Chung, Kyong Soo Park, Young Joo Park
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Expression and Purification of Phospholipase C-beta4, and Chimeric Phospholipase C and Characterization of Them.: Do Joon Park; Endocrinol Metab. 2012;27(4):282-288. Published online December 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.4.282

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Abstract PDF: BACKGROUND
Phospholipase C-beta4 (PLC-beta4) is known to be one of the most important signal transducing molecules; however, its biophysical and chemical characteristics are not well known due to the difficulty in purifying PLC-beta4 from bovine retina. In the present study, we used the baculovirus expression system in order to express and purify large amounts of PLC-beta4. With this system, we also tried to produce chimeric PLC-beta3/beta4 and PLC-beta4/beta3 protein in order to study the structure-activity relationship between N terminal and C terminal portion of PLC-betas. METHODS: I cloned PLC-beta4 to the baculovirus expression system by the polymerase chain reaction method and infected the PLC-beta4 to Sf9 cells. I purified recombinant PLC-beta4 proteins using sequential high performnance liquid chromatography (HPLC) by using the TSK phenyl-5PW column and the TSK heparin-5PW column. With this similar method, I was able to express chimeric PLC-beta3/beta4 and PLC-beta4/beta3 proteins. RESULTS: With the two step HPLC, I was able to purify PLC-beta4 by 30-fold; this purified PLC-beta4 contained PLC activity. I also expressed chimeric PLC-beta3/beta4 and PLC-beta4/beta3 using the baculovirus system, and their expression was confirmed by the immunoblot method. However, chimeric PLC-beta4/beta3 did not show PLC activity, while chimeric PLC-beta3/beta4 retained its PLC-activity. CONCLUSION: Expression of chimeric PLC-beta4 using the baculovirus system was an efficient method to obtain a large amount of protein. Moreover, this expression and purification method would be useful in studying the physical and chemical characteristics of this protein. In my study using chimeric PLC-beta protein by swapping the N terminal and C terminal portions of PLC-beta3 and beta4, chimeric protein lost its activity completely in PLC-beta4/beta3 chimera. This result suggested a minute change in the tertiary structure of the protein, which may significantly affect its function.

Effect of Thyroid Hormone to the Expression of Bile Salt Export Pump.: Hwa Young Ahn, Kwan Jae Lee, Soon Hui Kim, Eun Ky Kim, Ah Reum Kang, Jung Ah Lim, Ji Won Yoon, Kyung Won Kim, Do Joon Park, Bo Youn Cho, Young Joo Park; Endocrinol Metab. 2011;26(3):232-238. Published online September 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.3.232

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Abstract PDF

BACKGROUND
Bile acids were important for the regulation of cholesterol homeostasis. Thyroid hormone increased the expression of CYP7A1 (cholesterol 7alpha-hydroxylase), catalyzing the first step in the biosynthesis of bile acids. However, the effect of thyroid hormone on bile acid export has not been previously assessed. The principal objective of this study is to evaluate the effects of thyroid hormone on the bile salt export pump (BSEP). METHODS: Thyroid hormone, T3 (1 mg/g) was administered to male mice via intraperitoneal injection. After 6 hours and 5 days of T3 treatment, we measured serum total and LDL cholesterol and hepatobiliary bile acid concentrations. We assessed the changes associated with bile acid synthesis and transport. In order to evaluate the direct effect of thyroid hormone, we assessed the changes in the levels of BSEP protein after T3 administration in human hepatoma cells. RESULTS: Serum total and LDL cholesterol were reduced and hepatobiliary bile acid concentrations were increased following T3 treatment. Expressions of Cyp7a1 and BSEP mRNA were increased following T3 treatment. The levels of the BSEP protein in the mouse liver as well as in the human hepatoma cells were increased after T3 treatment. CONCLUSION: Thyroid hormone can regulate LDL cholesterol metabolism. It increases bile acid synthesis and the excretion of bile acids via increased BSEP expression.

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Hypothyroidism Increases Cholesterol Gallstone Prevalence in Mice by Elevated Hydrophobicity of Primary Bile Acids
Irina Kube, Luca Bartolomeo Tardio, Ute Hofmann, Ahmed Ghallab, Jan G. Hengstler, Dagmar Führer, Denise Zwanziger
Thyroid.2021; 31(6): 973. CrossRef
Thyroid Dysfunction and Cholesterol Gallstone Disease
Irina Kube, Denise Zwanziger
Experimental and Clinical Endocrinology & Diabetes.2020; 128(06/07): 455. CrossRef
Thyroid hormone receptor β1 stimulates ABCB4 to increase biliary phosphatidylcholine excretion in mice
Julien Gautherot, Thierry Claudel, Frans Cuperus, Claudia Daniela Fuchs, Thomas Falguières, Michael Trauner
Journal of Lipid Research.2018; 59(9): 1610. CrossRef

Association of the Parathyroid Adenoma Volume and the Biochemical Parameters in Primary Hyperparathyroidism.: Yul Hwang-Bo, Jung Hee Kim, Jee Hyun An, Eun Shil Hong, Jung Hun Ohn, Eun Ky Kim, Ah Reum Khang, Sun Wook Cho, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Chan Soo Shin; Endocrinol Metab. 2011;26(1):62-66. Published online March 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.1.62

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Abstract PDF

BACKGROUND
The objective of this study is to demonstrate the relationship between the volume of a parathyroid adenoma and the preoperative biochemical parameters in patients undergoing surgery for primary hyperparathyroidism. METHODS: The medical records of 68 patients who underwent a parathyroidectomy for a single parathyroid adenoma were retrospectively reviewed. The volume of the adenoma was estimated using its measured size and a mathematical formula. The correlation between the volume of the parathyroid adenoma and the preoperative laboratory data was assessed. RESULTS: There were no correlations between the estimated volume of the adenoma and the serum calcium, alkaline phosphatase and parathyroid hormone levels. However, the volume of the adenoma was associated with the preoperative level of serum phosphorus. After excluding 5 adenomas with cystic degeneration, a positive correlation was noted between the adenoma volume and the preoperative levels of alkaline phosphatase and parathyroid hormone. CONCLUSION: The preoperative serum levels of calcium, alkaline phosphatase and parathyroid hormone are of limited use to predict the volume of the parathyroid adenoma in patients with a single parathyroid adenoma. We suggest that the absence of a correlation between the volume of the adenoma and the biochemical parameters can be attributed to the cystic degeneration of the adenomas.

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Seda TURGUT, Ezgi Başak ERDOĞAN
OSMANGAZİ JOURNAL OF MEDICINE.2020;[Epub] CrossRef
Letter: Association of the Parathyroid Adenoma Volume and the Biochemical Parameters in Primary Hyperparathyroidism (Endocrinol Metab 26:62-66, 2011, Yul Hwang-Bo et al.)
Dong Jin Chung
Endocrinology and Metabolism.2011; 26(2): 185. CrossRef

Editorial

Expression of miRNA 146a/b, 221 and 222 in Thyroid Cancer.: Do Joon Park; J Korean Endocr Soc. 2009;24(1):15-16. Published online March 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.1.15

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Abstract PDF: No abstract available.

Case Reports

Mediastinal Uptake Misinterpreted as Metastasis in Papillary Thyroid Cancer.: Eun Kyung Lee, Kyung Won Kim, So Yeon Park, Young Joo Park, Young Tae Kim, June Key Chung, Hwa Young Cho, Yun Hyi Ku, Hee Suk Min, Seong Hoe Park, Do Joon Park, Bo Youn Cho; J Korean Endocr Soc. 2007;22(6):460-464. Published online December 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.6.460

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Abstract PDF

Radioactive iodine (RAI) therapy is used for the removal of remnant thyroid tissue or metastatic thyroid cancer cells in differentiated thyroid cancer. The main mechanism of the therapy is destruction of cells by radioactive iodine that penetrates the cells though the action of the sodium-iodide symporter (NIS). We experienced a case of a 26-year-old woman with mediastinal uptake as detected on a radioiodine scan, who was previously diagnosed with papillary thyroid cancer. For diagnostic tests including chest computed tomography (CT) and a radioiodine scan, the stimulated thyroglobulin level did not show a definite cause of the mediastinal uptake. During regular follow-up, the thymus became triangular with clear margins. The patient had neither specific symptoms nor physical findings related to the presence of a thymic mass. A subsequent CT scan showed an irregular margin of the thymus, suggestive of thymic metastasis. The patient underwent a mediastinectomy. The removed specimen was composed of normal thymic tissue. Moreover, we demonstrated the presence of human NIS by immunohistochemical analysis. After thymectomy, the mediastinal uptake was markedly decreased as compared to the previous scan. This case suggests that a clinician should be suspicious for the functional uptake of thymus when metastasis is unlikely in a clinical situation.

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Clinical Significance of Diffuse Intrathoracic Uptake on Post-Therapy I-131 Scans in Thyroid Cancer Patients
Hyun Su Choi, Sung Hoon Kim, Sonya Youngju Park, Hye Lim Park, Ye Young Seo, Woo Hee Choi
Nuclear Medicine and Molecular Imaging.2014; 48(1): 63. CrossRef

Clinical Characteristics for 132 Patients with Adrenal Incidentaloma.: Hyun Seung Jeong, Hee Joung Kim, Hae Sung Kim, Sang Wan Kim, Chan Soo Shin, Do Joon Park, Kyung Soo Park, Hak Cheol Jang, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2007;22(4):260-265. Published online August 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.4.260

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Abstract PDF

BACKGROUND
Recently, the detection rate for adrenal incidentaloma in Korea has been on the increase. We describe here the clinical characteristics of these tumors and describe appropriate guidelines of diagnosis and treatment. METHODS: We analyzed age, sex, location, size, function, and the pathological findings for 132 patients with an adrenal mass by CT, USG, and MRI undertaken for health examinations or non-adrenal disease from January 2000 to March 2005. RESULTS: Adrenal masses were most commonly found in patients in their sixties (31%). 62.1% of the patients were men and 37.9% were women. For the location of the masses, 53% were found in the left gland, 43.2% were found in the right gland and 3.8% were found in both glands. Of all of the masses analyzed, 66% were 1 cm to 4 cm in size, and an adenoma-like appearance was the most common finding (69.7%) seen in images. All of the pheochromocytomas and carcinomas were above 4 cm in size. Patients with a functional mass were seen in 18 cases (13.6%) and pheochromocytomas were seen in 12 cases (67%). Three patients were found with cancer (2.3%), two cases (1.5%) of a primary carcinoma and one case of a metastasis (0.8%). CONCLUSION: The frequency and characteristics of benign nonfunctional, functional and malignant masses that were found in our hospital were similar to those presented in studies conducted outside of Korea. Therefore, it may be possible to apply previously established guidelines to domestic patients.

Citations

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Adrenal incidentalomas: A seven-year follow-up single-center experience
Danijela Radojković, Milica Pešić, Milan Radojković, Saša Radenković, Vojislav Ćirić, Ivan Ilić, Miloš Stević
AFMN Biomedicine.2024; 41(2): 252. CrossRef
Guidelines for the Management of Adrenal Incidentaloma: the Korean Endocrine Society, Committee of Clinical Practice Guidelines
Jung-Min Lee, Mee Kyoung Kim, Seung-Hyun Ko, Jung-Min Koh, Bo-Yeon Kim, Sang-Wan Kim, Soo-Kyung Kim, Hae-Jin Kim, Ohk-Hyun Ryu, Juri Park, Jung-Soo Lim, Seong Yeon Kim, Young Kee Shong, Soon Jib Yoo
The Korean Journal of Medicine.2017; 92(1): 4. CrossRef
Clinical Guidelines for the Management of Adrenal Incidentaloma
Jung-Min Lee, Mee Kyoung Kim, Seung-Hyun Ko, Jung-Min Koh, Bo-Yeon Kim, Sang Wan Kim, Soo-Kyung Kim, Hae Jin Kim, Ohk-Hyun Ryu, Juri Park, Jung Soo Lim, Seong Yeon Kim, Young Kee Shong, Soon Jib Yoo
Endocrinology and Metabolism.2017; 32(2): 200. CrossRef
Clinical Characteristics for 348 Patients with Adrenal Incidentaloma
Jongho Kim, Kwi Hyun Bae, Yeon Kyung Choi, Ji Yun Jeong, Keun Gyu Park, Jung Guk Kim, In Kyu Lee
Endocrinology and Metabolism.2013; 28(1): 20. CrossRef
Clinical characteristics and follow-up of Korean patients with adrenal incidentalomas
Yoon Young Cho, Sunghwan Suh, Ji Young Joung, Hyemin Jeong, Dongmo Je, Hongseok Yoo, Taek Kyu Park, Yong-Ki Min, Kwang-Won Kim, Jae Hyeon Kim
The Korean Journal of Internal Medicine.2013; 28(5): 557. CrossRef
Characterization of Incidentally Detected Adrenal Pheochromocytoma
Soon Jib Yoo, Woohyeon Kim
Endocrinology and Metabolism.2012; 27(2): 116. CrossRef
Different diagnostic cut-off values of urinary fractionated metanephrines according to sex for the diagnosis of pheochromocytoma in Korean subjects
Seo Young Sohn, Hyung Doo Park, Soo Youn Lee, Jung Han Kim, Byong Chang Jung, Hye Jeong Kim, Hye Won Jang, Kwang Won Kim, Moon Kyu Lee, Yong Ki Min, Jae Hyeon Kim
Endocrine Journal.2012; 59(9): 831. CrossRef
Characterization of Incidentally Detected Adrenal Pheochromocytoma
Ye An Kim, Yul Hwangbo, Min Joo Kim, Hyung Jin Choi, Je Hyun Seo, Yenna Lee, Soo Heun Kwak, Eu Jeong Ku, Tae Jung Oh, Eun Roh, Jae Hyun Bae, Jung Hee Kim, Kyoung Soo Park, Seong Yeon Kim
Endocrinology and Metabolism.2012; 27(2): 132. CrossRef
The Evaluation and Follow-up of Adrenal Incidentaloma
Sin Gon Kim, Dong Seop Choi
Journal of Korean Endocrine Society.2007; 22(4): 257. CrossRef

Review Article

Management Guidelines for Patients with Thyroid Nodules and Thyroid Cancer.: Won Bae Kim, Tae Yong Kim, Hyuk Sang Kwon, Won Jin Moon, Jae Bok Lee, Young Sik Choi, Seok Ki Kim, Sun Wook Kim, Ki wook Chung, Jung Hwan Baek, Byung Il Kim, Do Joon Park, Dong Gyu Na, Jun Ho Choe, Jae Hoon Chung, Hye Seung Jung, Jeong Han Kim, Kee Hyun Nam, Hang Seok Chang, Woong Youn Chung, Soon Won Hong, Suck Joon Hong, Jeong Hyun Lee, Ka Hee Yi, Young Suk Jo, Ho Cheol Kang, Minho Shong, Jin Woo Park, Jong Ho Yoon, Seong Joon Kang, Kwang Woo Lee; J Korean Endocr Soc. 2007;22(3):157-187. Published online June 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.3.157

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Abstract PDF

No abstract available.

Citations

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Nuclear Medicine and Molecular Imaging.2025; 59(1): 8. CrossRef
Nuclear Medicine Imaging in Differentiated Thyroid Cancer: Summary of the Korean Thyroid Association Guidelines 2024 from Nuclear Medicine Perspective, Part-I
So Won Oh, Sohyun Park, Ari Chong, Keunyoung Kim, Ji-In Bang, Youngduk Seo, Chae Moon Hong, Sang-Woo Lee
Nuclear Medicine and Molecular Imaging.2025; 59(1): 1. CrossRef
Reflections on the 2024 KTA Guideline and the Role of Radioiodine Therapy in Differentiated Thyroid Cancer
Minseok Suh, So Won Oh, Gi Jeong Cheon, June-Key Chung
Nuclear Medicine and Molecular Imaging.2025; 59(2): 95. CrossRef
Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules 2024
Young Joo Park, Eun Kyung Lee, Young Shin Song, Su Hwan Kang, Bon Seok Koo, Sun Wook Kim, Dong Gyu Na, Seung-Kuk Baek, So Won Oh, Min Kyoung Lee, Sang-Woo Lee, Young Ah Lee, Yong Sang Lee, Ji Ye Lee, Dong-Jun Lim, Leehi Joo, Yuh-Seog Jung, Chan Kwon Jung,
International Journal of Thyroidology.2024; 17(1): 208. CrossRef
Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024
Young Joo Park, Eun Kyung Lee, Young Shin Song, Bon Seok Koo, Hyungju Kwon, Keunyoung Kim, Mijin Kim, Bo Hyun Kim, Won Gu Kim, Won Bae Kim, Won Woong Kim, Jung-Han Kim, Hee Kyung Kim, Hee Young Na, Shin Je Moon, Jung-Eun Moon, Sohyun Park, Jun-Ook Park, J
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Updates in the 2024 Korean Thyroid Association Clinical Practice Guidelines for Differentiated Thyroid Cancer: from Diagnosis to Initial Treatment
Eun Kyung Lee
International Journal of Thyroidology.2024; 17(2): 259. CrossRef
2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules
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Ten Years of the Korean Thyroid Association: Achievement and Future
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Ultrasound and clinicopathological features of papillary thyroid carcinomas with BRAF and TERT promoter mutations
Soo Yeon Hahn, Tae Hyuk Kim, Chang Seok Ki, Sun Wook Kim, Soohyun Ahn, Jung Hee Shin, Jae Hoon Chung
Oncotarget.2017; 8(65): 108946. CrossRef
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Journal of Pathology and Translational Medicine.2017; 51(6): 521. CrossRef
Changes in standardized mortality rates from thyroid cancer in Korea between 1985 and 2015: Analysis of Korean national data
Yun Mi Choi, Won Gu Kim, Hyemi Kwon, Min Ji Jeon, Minkyu Han, Tae Yong Kim, Young Kee Shong, Sang Mo Hong, Eun‐Gyoung Hong, Won Bae Kim
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Head & Neck.2011; 33(5): 691. CrossRef
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Revised Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Thyroid Cancer
Ka Hee Yi, Young Joo Park, Sung-Soo Koong, Jung-Han Kim, Dong Gyu Na, Jin-Sook Ryu, So Yeon Park, In Ae Park, Chung-Hwan Baek, Young Kee Shong, Young Don Lee, Jaetae Lee, Jeong Hyun Lee, Jae Hoon Chung, Chan Kwon Jung, Seung-Ho Choi, Bo Youn Cho
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Revised Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Thyroid Cancer
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Ho-Cheol Kang
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Case Report

A Case of Primary Reninism Manifested by Hypertension with Hypokalemia.: Hyung Jin Choi, Eui Sil Hong, Young Min Cho, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2005;20(2):168-173. Published online April 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.2.168

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Abstract PDF

Primary reninism is a rare cause of hypertension manifesting along with hypokalemia. A high level of plasma renin activity and a high level of serum aldosterone are the whole markers of primary reninism. Upon making the diagnosis of primary reninism, other more common causes of aldosteronism must be differentiated, such as renovascular hypertension and primary aldosteronism. Primary reninism is commonly caused by juxtaglomerular cell tumor, which is one of the curable causes of hypertension, and this can be successfully treated by conservative surgery. We report here on a case of primary reninism that was caused by juxtaglomerular cell tumor that developed in a 22-year-old female patient. She was recently diagnosed with hypertension and hypokalemia. She had markedly elevated plasma renin activity and an increased serum aldosterone concentration. Computed tomography revealed a mass located in the right kidney and selective renal vein sampling suggested that the mass was secreting an excess of renin. Right nephrectomy was done and her hypertension with hypokalemia was successfully treated. We report here a case of primary reninism that presented with juxtaglomerular cell tumor along with a review of the literature

Citations

Citations to this article as recorded by

Reninoma: a rare cause of curable hypertension
Ji Hye Kim, Ji Hyun Kim, Myung Hyun Cho, Eujin Park, Hye Sun Hyun, Yo Han Ahn, Hee Gyung Kang, Kyung Chul Moon, Il-Soo Ha, Hae Il Cheong
Korean Journal of Pediatrics.2019; 62(4): 144. CrossRef

Original Article

The Efficacy of MIBG Scan as a Diagnostic and Docalization Test for Pheochromocytoma.: Cheol Ku Park, Kyeong Won Kim, Do Hee Kim, Jae Hyeon Kim, Jun Gu Kang, San Wan Kim, Young Min Cho, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Bo Youn Cho, Hong Kyu Lee, Seong Yeon Kim; J Korean Endocr Soc. 2005;20(1):21-28. Published online February 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.1.21

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Abstract PDF: BACKGROUND
Computed tomography(CT) is currently considered as the initial imaging procedure of choice for the localization of pheochromocytomas in most of the cases. 131I-or 123I-Metaiodobenzylguanidine scintigraphy(MIBG scan) was proven to be a highly specific tool for the detection of adrenal and extra-adrenal pheochromocytomas, but was less sensitive than CT. The present study is aimed to evaluate the usefulness of a MIBG scan in diagnosis and localization of pheochromocytoma when compared to CT. METHODS: We retrospectively evaluated 27 patients who underwent a MIBG scan for a pheochromocytoma at the Seoul National University Hospital from the year 2000 and 2002. According to the pathological and clinical findings, in 16 the patients pheochromocytoma was confirmed to be positive and the rest 11 of the patients were excluded from the study. RESULTS: Pheochromocytomas was identified in 16 patients. Eleven of them were localized in adrenal gland and 5 were extra-adrenal lesions. The sensitivity to MIBG scan in adrenal lesions and extra-adrenal lesions, was 72%(8/11) and 40%(2/5) respectively. In our study, the overall sensitivity to MIBG scan was 62%(10/16), and overall specificity was 90.9%(10/11). By CT four were identified to have equivocal biochemical abnormalities, but were definite and extraadrenal tumors by MIBG scan showed abnormal uptakes in two of them. CONCLUSION: The MIBG scan was especially useful in 2 of the 27 patients but we had no experienced about the additional benefits of a MIBG scan in the other 25 cases. Our results reveal that a MIBG scan should be performed carefully for the diagnosis and localization of a pheochromocytoma, while considering cost and time of operation.

Evaluation Studies

Diagnostic Value of 24-hours Urinary Total Metanephrine As a Screening Test of Patients with Suspected Pheochromocytoma.: Sang Wan Kim, Kyung Won Kim, Do Joon Park, Chan Soo Shin, Kyung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2005;20(1):12-20. Published online February 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.1.12

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Abstract PDF: BACKGROUND
A pheochromocytoma is a rare cause of secondary hypertension. Its diagnosis is important as the hypertension is usually curable by resection of the tumor, whereas the condition is potentially lethal if undetected. Biochemical confirmation of excessive catecholamine production is a prerequisite to a definitive diagnosis. Various studies from other countries have indicated that measuring of the urinary metanephrine, using a specific procedure, is the single most reliable screening test for all patients suspected of having a pheochromocytoma. However, the diagnostic value of urinary metanephrine has never been reported in Korea. We investigated the diagnostic value of 24-hours urinary metanephrine in patients with a suspected pheochromocytoma. METHODS: This was a retrospective evaluation study, which included 95 patients with sustained hypertension and paroxysmal symptoms, and 38 patients with asymptomatic adrenal incidentaloma at Seoul National University Hospital, between July 2000 and October 2002. We performed the 24- hour urinary total metanephrine test on all patients. The diagnosis of a pheochromocytoma was applied only when confirmed by pathological analysis of a resected specimen. The possibility of a pheochromocytoma was ruled out when all biochemical tests were normal, which were performed at least in duplicate, or there was no evidence of a mass in abdominal radiological studies or histological verification. We determined the upper reference limit for urinary metanephrine as 1.3mg/day and calculated the sensitivity and specificity of the 24-hour urinary metanephrine test. RESULTS: Seventeen patients were diagnosed with a pheochromocytoma. The total metanephrine measurement had sensitivities and specificities of 82.4 and 73.3% in all the patients, 90.9 and 66.7% in patients with hypertension and paroxysmal symptoms, and 66.7 and 90.6% in patients with adrenal incidentaloma, respectively. CONCLUSION: The urinary total metanephrine measurement had relatively lower sensitivities and specificities than in other countries(sensitivity: 83~100%, specificity: 80~98%). The sensitivity of urinary metanephrine was relatively high in patients with hypertension and paroxysmal symptoms, and the specificity was high in patients with an adrenal incidentaloma. We suggest that normetanephrine and metanephrine should be separately measured, and a reasonable upper reference limit be used. It may also be necessary to measure urinary metanephrine together with urinary catecholamine or VMA to improve the diagnostic value of the urinary metanephrine test.

Original Articles

Relationship between Adiponectin, Leptin and Body Fat in Men with Hypogonadism Before and After Testosterone Treatment.: Sang Wan Kim, Joon Ku Kang, Do Joon Park, Chan Soo Shin, Kyung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2004;19(5):473-484. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Testosterone replacement therapy in men with hypogonadism improves sexual function, decreases body fat, and increases the mass and function of lean muscle. These beneficial effects of testosterone replacement therapy are accompanied by slight lowering of the high density lipoprotein (HDL) cholesterol levels, increase in the hematocrit/hemoglobin ratio and size of the prostate gland. It is presently unknown whether the effect of testosterone on body fat could also reduce the risk of atherosclerotic disease associated with obesity. We investigated the relationship between body fat and blood leptin and adiponectin levels to elucidate the effect of testosterone on body fat metabolism, as well as the effect of testosterone on lipid and bone metabolism. METHODS: We selected 28 men, who were hypogonadal (mean serum testosterone+/-SD, 22.3+/-35.3 ng/dL) due to an organic disease, and them with oral testosterone (testosterone undecanoate) for 12 months. We measured the body composition, serum leptin, plasma adiponectin, biochemical bone markers, bone mineral density, prostate-specific antigen, and serum lipids before and 3, 6 and 12 months after treatment. We analyzed the relationship between body fat and blood leptin and adiponectin levels. RESULTS: The mean serum testosterone concentration reached the subnormal range after 6 months of treatment, which remained for the duration of treatment. The fat mass decreased and muscle mass increased, not within the first 6 months, but principally within 12 months (p<0.05). Although the decrease in the serum leptin level was not statistically significant, there were positive correlations between the leptin level and fat mass before and after 6 months of treatment (p<0.05). The plasma adiponectin did not increase or correlate with body fat parameters. The bone mineral densities of the lumbar spine (L2-L4) and femoral neck did not increased, but the serum osteocalcin and urine N-telopeptide were significantly decreased (p<0.05 and <0.01, respectively). The HDL-cholesterol decreased, principally within the first 6 months (p<0.01), but the total and LDL cholesterols, and the triglycerides remained unchanged during the course of treatment. There was also no change in prostate-specific antigen. CONCLUSION: Twelve months of oral testosterone replacement in men with hypogonadism improved body composition and bone metabolism, but demonstrated subnormal serum testosterone levels, had no effect on the leptin and adiponectin levels and decrease in HDL-cholesterol levels. It will be necessary to examine the long-term effects of testosterone replacement on the incidence of cardiovascular events as well as cardiovascular risk factors in men with hypogonadism

The Aging-related Change of Responses to TSH in Thyroid Cells.: Young Joo Park, Tae Yong Kim, Ji Eun Kim, Young Cheol Kim, In Kyeong Chung, Chan Soo Shin, Do Joon Park, Kyoung Soo Park, Seong Yeon Kim, Sang Chul Park, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2004;19(2):141-151. Published online April 1, 2004

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Abstract PDF: BACKGROUND
To understand the mechanism of aging-related changes of the thyroid, the differentiated functions and growth of thyroid cells in response to TSH were investigated using aged or young thyrocytes. METHODS: FRTL-5 cells, with less than 10 or more than 45 passages, were used. After treatment with 1 U/L TSH or 1-100 mM NaI, the cAMP generation, iodide uptake, cellular proliferation or the expression of NIS mRNA or protein were measured. Sprague-Dawley rats were sacrificed at 5 and 16 weeks and 23 months, and their thyroids used for Northern blot analysis or immunohistochemistry of NIS. RESULTS: There were no differences in cAMP generation, iodide uptake, the proportions of G1/M or S phase, or intracellular DNA contents between the young and aged cells at basel levels. After TSH stimulation, these were increased in dose-dependent manners, with larger increments in the young cells. The changes in the NIS mRNA expression were similar in both the young and aged cells, but to a greater extent in the young cells. A similar phenomenon was observed in rat. However, the amount or intracellular distribution of NIS protein was not different. There was also no difference in the function or expression of NIS after treatment with a high dose of iodide. CONCLUSION: The aging-related decrease in the generation of cAMP might be thought of as one of the mechanisms of the decrement of iodide uptake or cellular proliferation with aging. The decreased expression of NIS mRNA seems to be the most important mechanism for the decreased iodide uptake capacity

Case Report

A Case of Acute Suppurative Thyroiditis Caused by Pyriform Sinus Fistula with Thyrotoxicosis.: Kyung Won Kim, Young Joo Park, Tae Yong Kim, Min Kyung Moon, Sae Won Han, Cheon Jung Eun, Young A Kim, Tae Hoon Jin, Hee Soon Chung, Do Joon Park, Bo Youn Cho; J Korean Endocr Soc. 2004;19(1):69-75. Published online February 1, 2004

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Abstract PDF: This is the first case report about acute suppurative thyroiditis with thyrotoxicosis and pyriform sinus in Korea. A female patient, who was previously healthy, visited our hospital for the treatment of common cold symptoms and neck pain which developed 2 weeks before the visit. The condition of the patient did not improve through the use of antipyretics and even worsened. The patient was admitted to the hospital and was diagnosed with acute suppurative thyroiditis. The culture result of the drained fluid revealed group D Streptococcus. The patients condition was improved after using antibiotics and drainage. After recovery from acute thyroiditis, esophagography was performed and the pyriform sinus was found to be obliterated by chemical cauterization. It is very important yet difficult to differentiate acute thyroiditis with thyrotoxicosis from subacute thyroiditis. In this study, we discussed the differential diagnosis between acute thyroiditis and subacute thyroiditis with a review of literature.

Original Articles

Diagnostic Value of 1microgram Rapid ACTH Stimulation Test According to the Timing of Sampling of Serum Cortisol in Patients with Suspected Central Adrenal Insufficiency.: Sang Wan Kim, Young Min Cho, Do Joon Park, Chan Soo Shin, Kyung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2004;19(1):33-41. Published online February 1, 2004

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Abstract PDF: BACKGROUND
Traditional testing of the hypothalamic-pituitary-adrenal axis function has essentially relied upon the insulin tolerance test or the metyrapone test(both tests are not only uncomfortable, but are also dangerous). The standard ACTH stimulation test uses an extremely supra-physiologic amount(250f microgram) of ACTH to evaluate a physiological response, which may result in a false normal response. The 1microgram rapid ACTH stimulation test is more physiological and more sensitive than the standard test, but there exist much controversy about when the serum cortisol should be measured or what the most appropriate cut-off point is for normality or whether the 1microgram ACTH commercial solution is needed. The aims of this study were to investigate 1) whether 1microgram of ACTH is an appropriate amount to stimulate the adrenal gland of patients that have suspected central adrenal insufficiency compared with insulin tolerance test(ITT) and 2) the diagnostic value of the 1microgram rapid ACTH stimulation test according to timing of sampling of serum cortisol. METHODS: In order to evaluate the dose-response relationship between ACTH and cortisol, we performed the ITT in 77 patients with suspected central adrenal insufficiency with serial measurements of serum cortisol and plasma ACTH. We drew the blood samples in 10 min intervals between 10 and 60 min after the administration of 1microgram ACTH in 39 patients with central adrenal insufficiency and in 38 pituitary control patients with pituitary. ITT was used to confirm the diseases for the patients of central adrenal insufficiency, but for pituitary control patients, the ITT indicated normality in the patients. Also, all subjects underwent the 250microgram rapid ACTH stimulation test, and we compared the diagnostic value of the 1microgram ACTH stimulation test with the 250microgram test. RESULTS: 1) The plasma ACTH level after the 1microgram ACTH stimulation test, even if it was be assumed as approximately 300pg/mL, was expected to be sufficient enough to stimulate the adrenal cortex normally(serum cortisol levels >18microgram/dL) compared to the plasma ACTH level in the ITT. 2) The sensitivity and specificity of the 1microgram rapid ACTH stimulation test was highest with 92.3% and 84.2%, respectively, when serum cortisol levels were measured at 20, 30, and 40 min after the ACTH injection. The 1microgram rapid ACTH stimulation test was more sensitive than the 250microgram ACTH test(sensitivity: 92.3%, specificity: 71.8%). CONCLUSION: The 1microgram rapid ACTH stimulation test was more sensitive test in patients with suspected central adrenal insufficiency, and blood samples for cortisol levels should be drawn at 20, 30, and 40 min after ACTH administration.

Determination of Glucocorticoid Replacement Therapy and Adequate Maintenance Dose in Patients with Secondary Adrenal Insufficiency.: Sang Wan Kim, Hye Seung Jung, Seong Hee Kwon, Do Joon Park, Chan Soo Shin, Kyung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2003;18(5):456-464. Published online October 1, 2003

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Abstract PDF: BACKGROUND
Determination of the adequate dose of glucocorticoid replacement therapy, in patients with secondary adrenal insufficiency, is of great importance to avoid the consequences of under or over treatment. The aims of this study were: 1) to assess the value of adrenal cortical function tests in determining whether glucocorticoid replacement should be given, and 2) to investigate the adequate maintenance dose of glucocorticoid in patients with secondary adrenal insufficiency. METHODS: Forty patients, with secondary adrenal insufficiency, confirmed by the insulin-induced hypoglycemia test (IHT), were studied. All subjects underwent basal serum cortisol measurement, IHT and 250 g rapid ACTH stimulation tests (AST). The clinical usefulness of these tests, for the determination of glucocorticoid replacement therapy, was evaluated in patients with secondary adrenal insufficiency. 26 of the 40 patients had received prednisolone (Pd) (5 mg per day) replacement due to symptoms from adrenal insufficiency. The dose of Pd was serially changed from 5 to 3.75, and then to 6.25 mg per day, every 3 month. The measured lipid parameters, serum osteocalcin and urinary N-telopeptide were measured and the quality of life evaluated by the administration of an Addisonian questionnaire, both before and after the dose changes. RESULTS: 1) For all tests, cut-offs were selected that would provide adequate specificity and sensitivity. When the cut-offs were set to provide 95% specificity, the corresponding sensitivitycut-off values, obtained with basal serum cortisol, peak serum cortisol in IHT and AST were: 88.4% <5 microgram/dL, 80.7% <11 microgram/dL and 76.9% <16 microgram/dL. 2) The urinary type I collagen N-telopeptide, total cholesterol, HDL- and LDL-cholesterol levels were significantly increased, and the serum osteocalcin levels significantly decreased when the daily dose of Pd was increased to 6.25 from 3.75 or 5 mg. The LDL-cholesterol levels especially, were significantly increased, even though the change in the Pd from 3.75 to 5 mg per day was subtle. CONCLUSION: The basal cortisol levels, HPA axis tests and the symptoms of patients may be helpful to determine whether prednisolone replacement therapy should be given. It is suggest that an adequate dose of glucocorticoid replacement therapy should be not exceed Pd 5mg per day, so as not to have adverse effects on the bone and lipid metabolisms.

Crosstalk Between cAMP and Phosphoinositide System in Signal Transduction Pathways Through TSH Receptor.: Byung Sool Moon, Young Joo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Do Joon Park; J Korean Endocr Soc. 2003;18(4):404-413. Published online August 1, 2003

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Abstract PDF: BACKGROUND
TSH stimulates both the adenyl cyclase and phospholipase C (PLC) pathways by binding to a single cell surface receptor that is coupled to G protein, and we examined crosstalk between these two signaling pathways. METHODS: FRTL-5 rat thyroid cells were grown in 6H medium, then incubated with 5H medium before the stimulation. Then cells were incubated for 24 hours with 5H mix containing 1 mCi/L myo-(2-N-3H) inositol. After pretreatment of 100 microM Rp-cAMP, 100 microM forskolin, 50 nM staurosporine, or 100 nM PMA (phorbol-12-myristate-13-acetate), TSH were added in different experiments. After 30 min at 37 degrees C, cells were disrupted and IP formation was determined. RESULTS: Stimulation with 100 microU/mL TSH resulted in a 1.65 fold increase in IP generation. In pursuing the possibility that the two post-receptor events might be linked in some way, we examined the effect of exogenously administrated Rp-cAMP, protein kinase A antagonist, and forskolin, a direct stimulant of protein kinase A, on IP generation achieved at a dose of 100 microU/mL TSH. The pretreatment of 100 M Rp-cAMP at a concentration sufficient to inhibit protein kinase A enhanced TSH-induced IP production. This effect of Rp-cAMP was dose-dependent. Forskolin attenuatedTSH-stimulated increases in phosphatidylinositide turnover. PMA, a protein kinase C (PKC) activator and staurosporine, a PKC inhibitor did not affect TSH-induced IP generation. CONCLUSION: These data suggested that activation of adenylate cyclase/cAMP post-receptor signalling casacde, which results in the protien kinase A activation, has an inhibitory effect on IP turnover activated by TSH.

Case Report

A Case of Renal Cell Carcinoma with Thyroid Metastasis.: Hye Seung Jung, Young Joo Park, Hee Sun Chung, Mee Soo Chang, Tae Hoon Jin, Cheol Soo Choi, Sung Woo Park, Tae Young Kim, Do Joon Park, Bo Youn Cho; J Korean Endocr Soc. 2003;18(3):318-324. Published online June 1, 2003

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Abstract PDF: Metastatic thyroid cancer is uncommon but must be distinguished from primary thyroid cancer because of the differences in management and prognosis. Although renal cell carcinoma is one of the most common tumors that metastasize to the thyroid gland, such a case has never been reported in Korea. We describe the first case of metastatic renal cell carcinoma in the thyroid gland. A 66-year-old man presented with a neck mass detected about 6 weeks previously. He had undergone left nephrectomy due to renal cell carcinoma 8 years before and had remained disease-free thereafter. Computed tomography of the neck showed a 5 cm-sized thyroid mass. Fine needle aspiration cytology revealed some malignant cells containing intranuclear inclusions which were assumed to be papillary thyroid carcinoma. The patient underwent total thyroidectomy. Histologic diagnosis of the thyroid mass was metastatic renal cell carcinoma and further evaluation with chest computed tomography showed two enlarged mediastinal lymph nodes suggesting metastases. The previous history of malignancy should be scrutinized when managing a thyroid mass in patients with a prior or concomitant malignancy, and the possibility of metastasis should be carefully considered.

Original Article

Interaction of Pituitary Adenylate Cyclase-Activating Polypeptide and Angiotensin II on Aldosterone Production in Human Adrenocortical H295R Cells.: Seong Yeon Kim, Sang Wan Kim, Young Min Cho, Do Joon Park, Chan Soo Shin, Kyung Soo Park, Bo Youn Cho, Hong Kye Lee; J Korean Endocr Soc. 2003;18(3):272-282. Published online June 1, 2003

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Abstract PDF: BACKGROUND
Evidence is accumulating that aldosterone secretion can be regulated in a paracrine and/or an autocrine manner by several neuropeptides locally released within the adrenal gland. Among neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) is present in high concentration in the human adrenal gland. The purpose of this study was to investigate the action of PACAP and the interaction between PACAP and angiotensin II (AII), the main physiologic aldosterone secretagogue, in aldosterone production in human H295R adrenocortical cells. METHODS: H295R cells were incubated with increasing concentrations of PACAP (10(-11)M~10(-7)M) in the absence or presence of 10(-7)M AII. Aldosterone concentration in the supernatant was determined by RIA. Intracellular cAMP content was measured by RIA and total inositol phosphate (IP) production by anion exchange chromatography. Gene expression of CYP11B2 was studied by RT-PCR. RESULTS: In H295R cells, PACAP stimulated aldosterone production in a dose-dependent manner. Incubation of H295R cells with PACAP in the presence of AII significantly increased aldosterone production, compared with that of PACAP alone. PACAP dose-dependently increased cAMP production, but 10(-7)M AII had no effect on either basal or PACAP-stimulated cAMP production. Total IP production was not affected by PACAP, but was increased by 10(-7)M AII; an increase that was not further increased by addition of PACAP. RT-PCR analysis of H295R cells which were exposed to 10-7M PACAP or 10(-7)M AII showed an increase in CYP11B2 transcript signal. Induction of CYP11B2 mRNA expression in response to treatment with both PACAP and AII was significantly more than that resulting from using PACAP alone. CONCLUSION: The present study demonstrates that PACAP exerts a direct stimulatory effect on aldosterone production through induction of CYP11B2 mRNA expression by adenylate cyclase activation as the main intracellular signal pathway in H295R cells. Furthermore, there may be some additive effects between PACAP and AII on aldosterone production.

Review Article

Expression and Rearrangement of RET in Thyroid Papillary Cancer.: Do Joon Park; J Korean Endocr Soc. 2003;18(3):268-271. Published online June 1, 2003

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Abstract PDF: No abstract available.

Case Reports

A Case of Syndrome of Resistance to Thyroid Hormone Associated with Mutation(M313T) in Thyroid Hormone Receptor Beta Gene.: Jae Kyung Hwang, Kyung Won Kim, Tae Yong Kim, Sang Wan Kim, Young Joo Park, Do Joon Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2003;18(2):206-213. Published online April 1, 2003

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Abstract PDF: Syndrome of resistance to thyroid hormone(RTH) is inherited by an autosomal dominant trait, and characterized by elevated thyroid hormone levels with reduced responsiveness of the pituitary and peripheral tissues to thyroid hormone action. All of the reported RTH patients have various mutations in the ligand-binding domain coding region of the thyroid hormone receptor beta gene. A 21-year-old man visited our hospital complaining of fatigue. He had mild thyroid goiter and intermittent palpitation. Thyroid function test showed elevated total T3, free T4, and TSH levels. Levels of TSH free a-subunit and basal pituitary hormones, except prolactin, were normal. MRI of the sellar region showed no abnormal finding. TSH response to TRH stimulation was normal, and TSH values to TRH stimulation after T3 suppression revealed partial response. Sequeuce analysis of the thyroid hormone receptor beta gene confirmed a heterozygous missense mutation in exon 9; and the amino acid alteration was a substitution of a threonine(ACG) for a methionine(ATG) at codon313. Sequeuce analysis of the parents showed no mutation.We report the first case of a man with RTH caused by a de novo mutation(M313T) in TRbeta gene, confirmed by sequeuce analysis.

A Case of Multiple Endocrine Neoplasia Type 2B associated with a M918T Mutation in RET Proto-Oncogene.: Tae Yong Kim, Jae Kyung Hwang, Min Kyong Moon, Young Joo Park, Do Joon Park, Seong Yeon Kim, Hong Kyu Lee, Yo Kyu Yoon, Bo Youn Cho; J Korean Endocr Soc. 2003;18(1):85-93. Published online February 1, 2003

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Abstract PDF: A multiple endocrine neoplasia type 2B(MEN2B) is the most distinct and aggressive form of the MEN type 2 variants. We report a case of a 24-years-old woman with MEN2B. The patient had previously undergone a Duhamel's operation due to a megacolon at 6 years old, minor surgery to remove small tumors on the lip at 8 years old, and a bilateral osteotomy of the femur, due to coxa valga, at 15 years old. She underwent a total thyroidectomy and neck dissection, due to a growing thyroid nodule, despite thyroxine treatment, at 19 years old. The pathology revealed a medullary thyroid carcinoma. There was no history of MEN 2B in her family. She had prominent lips, multiple oral mucosal masses, and marfanoid habitus. During the subsequent follow-up, a positron emission tomogram was taken due to a persistently high level of serum calcitonin, despite repeated neck dissections, which revealed a mass in the right adrenal gland. Adrenomedullary function tests showed high levels of urinary catecholamine metabolites, and a genetic analysis of the peripheral leukocyte showed a codon 918 mutation (Met918Thr) at exon 16 of the RET proto-oncogene. The patient underwent a right adrenalectomy and the pathology revealed a pheoch-romocytoma.

Original Articles

Regulatory Mechanism of p66 Shc Expression by TSH in FRTL-5 Cells.: Young Joo Park, Eun Shin Park, Tae Yong Kim, Yun Yong Lee, Seon Hwa Lee, Do Joon Park, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2003;18(1):45-55. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Thyroid goiters are very common, however, the mechanism of development is not fully understood. A TSH receptor has been known to activate two different signaling pathways the cAMP/protein kinase A(PKA) and phospholipase C(PLC)/protein kinase C(PKC) systems. However, both systems are limited in the degree to which they explain the discrepancy between a goiter and TSH receptor activation. It has recently been reported that the expression of p66 Shc was increased by TSH stimulation in thyrocytes, suggesting that the p66 Shc molecule may play a critical role in the transition of the TSH-induced growth signals. METHODS AND RESULTS: In this study, we examined the expression of p66 Shc by stimulation of TSH, and the regulatory mechanisms of the TSH-induced expression of the p66 Shc in FRTL-5 cells. In FRTL-5 cells, TSH could increase the expression of the p66 Shc, and the this expression was decreased to basal levels after the removal of TSH. The TSH-induced p66 Shc expression was competitively inhibited by TSH receptor blocking antibodies. The increments of the expression of the p66 Shc protein caused by TSH were both time and concentration dependent, and it was same in the mRNA levels. Cholera toxin increased the expression of the p66 Shc, while pertussis toxin did not. The activators of the cAMP/PKA pathway (8-bromo-cAMP and forskolin) also stimulated the expression of p66 Shc, and the PKA inhibitor H89 decreased the expression, while the inhibition of the PKC pathway by GF109203X, or PMA, affected the expression of p66 Shc very little. CONCLUSION: Our data suggests that p66 Shc may play an important role in regulating the growth of thyrocytes. The TSH receptor - Gs protein - adenylate cyclase - cAMP - PKA pathway mainly mediates the TSH effects on the expression of p66 Shc molecules.

Vitamin D Receptor Gene 3' End Polymorphisms in Patients with Graves' Disease in Koreans.: Jae Kyung Hwang, Kyung Won Kim, Tae Yong Kim, Hui Su Lee, Young Joo Park, Chan Soo Shin, Do Joon Park, Kyong Soo Park, Byung Doo Rhee, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2003;18(1):12-23. Published online February 1, 2003

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Abstract PDF: BACKGROUND
The aim of this study was to evaluate the association of vitamin D receptor (VDR) gene polymorphisms with Graves' disease in Koreans. We also investigated the association of VDR gene polymorphisms with the clinical characteristics and titers of TSH receptor antibodies in patients with Graves' disease. SUBJECTS AND METHODS: The VDR gene polymorphisms were evaluated in 117 patients with Graves' disease and 156 normal controls. The polymorphisms were represented according to restriction fragment length polymorphism; Aa(ApaI), Bb(BsmI) and Tt(TaqI), with the capital letters signifying the absence, and small letters the presence of restriction sites. RESULTS: The distribution of the ApaI polymorphism genotype was: AA(17.1%), Aa(50.4%) and aa(32.5%). The BsmI polymorphism genotype distribution was: BB(7.1%), Bb(35.4%) and bb(57.5%); and the TaqI polymorphism genotype distribution was: TT(92.6%), Tt(6.2) and tt(1.2%). No significant differences in either genotypic or allelic distributions were observed, between the patients with Graves' disease and the normal controls, associated with the VDR gene polymorphisms. No significant differences were observed with age, sex, size of goiter or the presence of ophthalmopathy, in patients with Graves' disease associated with the VDR gene polymorphisms. However, the titers of the TBII were significantly higher in the aa than the Aa genotype, and were also higher in the group without the A allele than in groups with(aa 55.9+/-18.3 vs. Aa 43.2+/-23.4, p<0.05; aa 55.9+/-18.3 vs. AA and Aa 42.9+/-23.5, p<0.05). Thyroid stimulating antibodies measured with a CHO cell transfected with a wild type of human TSH receptor, were also higher in patients without the A allele than in those with(aa 620+/-829 vs. AA and Aa 353+/-306, p<0.05). The titers of the anti-thyroglobulin antibodies were significantly higher in the groups not containing the B allele than in the group that did(bb 50.9+/-42.8 vs. BB and Bb 31.9+/-38.9, p<0.05). The serum alkaline phosphatase activities were higher in the group having the b allele than in the group that did not(Bb and bb 139+/-68 vs. BB 82.2+/-15.5, p<0.05). CONCLUSIONS: The VDR gene 3' end polymorphism was not associated with susceptibility to Graves' disease in Koreans. The studies of other polymorphism sites of the VDR gene might be required to elucidate the association of VDR gene polymorphisms with Graves' disease in Koreans.

Case Report

A Case of Acute Suppurative Thyroiditis as a Complication of Acupuncture in Patient with a Benign Thyroid Nodule.: Tae Yong Kim, Han Mo Yang, Jae Kyung Hwang, Young Min Cho, Young Joo Park, Do Joon Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2002;17(4):576-582. Published online August 1, 2002

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Abstract PDF: Acute suppurative thyroiditis is an uncommon disease, and usually affects patients with preexisting thyroid gland pathology. Penetrating injury could provide an acquired channel for the infection to spread into the relatively infection-resistant thyroid gland. We describe the first case of acute suppurative thyroiditis, as a complication of acupuncture, in a patient with a benign thyroid nodule. A 54-year-old male received acupuncture on his neck for the treatment of a previously diagnosed thyroid nodule. Four days after the acupuncture, the patient was admitted due to severe pain of the anterior neck and odynophagia. Fever and tenderness over the thyroid gland were observed. Burkholderia cepacia was isolated from a culture dish of aspirate of the thyroid gland. A neck computed tomography scan showed an abscess in the thyroid gland. Antibiotic treatment, and repeated drainage of the abscess, ameliorated the symptoms of infection. Two weeks after admission, the patient was discharged without sequela. Acupuncture should be considered as a kind of penetrating injury, which may induce acute suppurative thyroiditis.

Original Articles

The Effects of Iodide on the Cellular Functions and Expression of Thyroid Autoantigens in Thyroid Cells.: Young Joo Park, Eun Shin Park, Tae Yong Kim, Hye Seung Jung, Hyeong Kyu Park, Do Joon Park, Won Bae Kim, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2002;17(1):69-78. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Iodide has been known to control the function and the growth of the thyroid gland, and to be used as a substrate of thyroid hormone. Moreover, it has been suggested that excessive iodide stimulates the thyroid autoimmune responses. To evaluate the effects of iodide on thyrocytes, we investigated cell function and proliferation, or thyroid autoantigen expression after administering iodide to rats or FRTL-5 cells. MEHTODS AND RESULTS: Ten-weeks-old Sprague-Dawley rats were sacrificed after 7 days of NaI treatment. The expressions of thyroid autoantigens were examined by northern blot analysis. Chronic administration of iodide resulted in no effect on TSH receptor (TSHR) and thyroperoxidase (TPO) mRNA expression, while it increased thyroglobulin (TG) and diminished sodium-iodide symporter (NIS) mRNA expression. FRTL-5 cells were also treated with various concentrations of NaI. The generation of cAMP or iodide uptake was decreased, and the cellular growth was also inhibited by iodide. However, the expressions of all thyroid autoantigens (TSHR, TG, TPO, MHC class I and class II) except NIS were unchanged for 72 hours after iodide administration. The expression of NIS was mildly increased after 24 hours. CONCLUSION: Iodide resulted in decreased cell proliferation and cellular function of cAMP generation and iodide uptake. Chronic administration of iodide increased TG and diminished NIS mRNA expression in vivo but not in vitro

Effect of Class 2 Transactivator on Expression of Thyroid Transcription Factor-1 in FRTL-5 Cells.: Won Bae Kim, Tae Yong Kim, Young Joo Park, Jae Joon Koh, Do Joon Park, Bo Youn Cho; J Korean Endocr Soc. 2002;17(1):48-56. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Gamma-interferon (gamma-IFN) is known to suppress thyroperoxidase (TPO), thyroglobulin (Tg), thyrotropin receptor (TSHR) mRNA expression via unclarified mechanism. Thyroid transcription factor-1 (TTF-1) is a nuclear protein involved in the maximal expression and tissue specific expression of thyroid-specific antigens (TPO, Tg, TSHR, NIS) in thyrocytes. Although It's plausible that gamam-IFN induced suppression of thyroid-specific antigen expression may be mediated by decrease of TTF-1 expression, such an effect has not been documented yet. In this study we investigated the effect of gamma-IFN on the expression of TTF-1 in the rat thyroid cell, FRTL-5, and determined whether such an effect is mediated by sclass 2 transactivator (CIITA). METHEODS: The mRNA expression of TTF-1 was quantitated by northern blot analysis after treatment of gamma-IFN, and after expression of CIITA in FRTL-5 cells. Four different promoter constructs were made by cloning into the pRSV-luciferase vector, each contained 5'flanking sequence of different lengths (-5.18 kb, -4.11 kb, -1.94 kb, -1.15 kb) of rat TTF-1 gene. Effects of gamma-IFN and CIITA on promoter activities were analyzed by luciferase assay in FRTL-5 cells into which each promoter construct had been transfected by DEAE-dextran method. RESULTS: Steady state TTF-1 mRNA level at 48 h after gamma-IFN treatment (100 U/mL) was significantly decreased from that of the pre-treatment level (1.65+/-0.16 vs. unit, p<0.05). In all 4 promoter constructs gamma-IFN significantly suppressed promoter activities compared to the vector only transfected cells. CIITA expression in FRTL-5 cells significantly decreased the steady state TTF-1 mRNA level when compared to that in mock-transfected cells (1.69+/-0.31 vs. 1.17+/-0.44 arbitrary unit, p<0.05). CIITA expression in FRTL-5 cells caused suppression of promoter activities in -5.18 kb and -4.11 kb constructs, but had no effects on those activities in -1.94 kb; and -1.15 kb constructs. CONCLUSION: gamma-IFN, directly and indirectly via CIITA expression, suppressed the transcription of TTF-1 gene in the FRTL-5 cells. It may be one of the mechanisms involved in the gamma-IFN-induced suppression of thyroid-specific protein expressions in thyrocytes 1.25+/-0.27 arbitrary

Comparison of Treatment Modalities in Hyperprolactinemia.: Sun Hee Park, Hyeon Jeong Jeon, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2002;17(1):32-42. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Prolactinomas have been treated primarily with bromocriptine, a dopamine agonists, rather than by transsphenoidal pituitary adenomectomy. However, lower success rates, as well as intolerance or resistance to medical therapy, have been reported in some recent series. The purpose of this study was to compare the effects of surgery and bromocriptine in the treatment of prolactinomas patients. Also we investigated the natural history and effects of bromocriptine on patients with idiopathic hyperprolactinemia. METHEODS: We retrospectively compared the effects of treatment with surgery and with bromocriptine in 27 idiopathic hyperprolactinemia patients, 35 microprolactinoma patients and 61 macroprolactinoma patients. RESULTS: (1) In 14 patients with untreated idiopathic hyperprolactinemia, 8 (57%) achieved remission. In patients without remission, preoperative serum prolactin level was significantly higher than patients with remission (p<0.05). In 13 patients on bromocriptine, 11 (85%) achieved remission, while the other 2, taking bromocriptine irregularly because of side effects, had persistent hyperprolactinemia. (2) In 35 patients with microprolactinoma, 11 (30%) surgery as initial therapy and surgical remission was achieved in only 5 of the 11 (45%). In 23 patients on bromocriptine, 17 (74%) achieved remission. Among the 6 patients without remission, 5 patients took bromocriptine irregularly because of side effect. (3) In 61 patients with macroprolactinoma, 49 (80%) underwent surgery as initial therapy and surgical remission was achieved in only 9 of the 49 (18%). In 50 patients on bromocriptine, 30 (60%) achieved remission. Among the 20 patients without remission, 13 took bromocriptine irregularly because of side effect and 5 were resistant to bromocriptine. CONCLUSION: In idiopathic hyperprolactinemia, the requirement for medical treatment is doubtful because of a high tendency to ward spontaneous cure. In spite of the low success rate, surgery has been used as the primary therapy for prolactinoma in Korea. And yet, medical treatment with bromocriptine is superior to surgery. However, irrgular administration of medication due to drug side effects was the main cause of the low success rate. Therefore, the necessity for new drug development is emphasized

The Changes of Expression of Thyroid Specific Antigens in Aging.: Young Joo Park, Eun Shin Park, Tae Yong Kim, Sang Wan Kim, Hyeong Kyu Park, Do Joon Park, Won Bae Kim, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Sang Chul Park, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2001;16(4-5):457-466. Published online October 1, 2001

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Abstract PDF: BACKGROUND
With the prevalence of serum antithyroglobulin(anti-TG) and antithyroperoxidase(anti-TPO) autoantibodies increasing with age, it has been suggested that changes of thyroid autoimmunity with aging are associated with endemic iodine intake. To understand the mechanism of aging-related increases of thyroid autoimmune response, we investigated the expression of thyroid specific autoantigens of aged phenotype, and compared them with those of young phenotype both in vivo and in vitro. METHODS: Sprague-Dawley rats were sacrificed at 5, 10 and 16 weeks(young), and at 23 months(aged). Their FRTL-5 thyroid cells were harvested at cell passages less than 10(fresh) or more than 30 (aged). The expression of thyroid autoantigens, sodium-iodide symporter(NIS), TSH receptor (TSHR), TG and TPO, were examined by northern blot analysis. To evaluate the effects of iodide, 1mM of NaI was added to the medium for 24 hours, and following incubation the expressions of MHC class I and class II were also examined. RESULTS: The expressions of TPO were markedly increased in the aged rats, and those of TG were moderately. However, NIS and TSHR showed no differences in their expression levels between aged rats and young rats. In vitro, there were no differences in the expressions of TG or TPO, nor of NIS or TSHR, between aged cells and fresh cells. Neither did Iodide exhibit any influence on the expression of MHC molecules in aged cells or fresh cells. CONCLUSION: The expression levels of TPO and TG were increased in aged rats, which may partially explain the mechanism of increasing thyroid autoimmunity with age.

Early Detection of Medullary Thyroid Cancer by Screening of the RET Proto-oncogene Germ Line Point Mutation in Family Members Affected with Hereditary Medullary Thyroid Cancer .: Sun Wook Kim, Tae Yong Kim, Young Joo Park, Won Bae Kim, Chan Soo Shin, Do Joon Park, Kyoung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2001;16(1):54-64. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Conventional biochemical screening for family members with hereditary medullary thyroid cancer (MTC) is associated with problems of sensitivity and, specificity and it frequently detects gene carriers only after disease progression. Molecular genetic screening tests that detect germ-line point mutations of the RET proto-oncogene has changed our approach to hereditary MTC. In this study we screened members of a large Korean family that had a history of hereditary MTC by a molecular genetic method and propose a therapeutic approach in managing the disorder. METHODS: Using DNA acquired from peripheral blood leukocytes of the index patient, we performed PCR and direct sequencing of exon 10 of the RET proto-oncogene. PCR-RFLP using an Mbo II restriction enzyme was performed on family members who were at risk of MTC according to the family pedigree. Basal serum calcitonin level was determined in family members who had a point mutation of the RET proto-oncogene and a pentagastrin stimulation test was performed in 3 members. RESULTS: Genetic analysis in the index case revealed a mutation in exon 10, codon 618 of the RET proto-oncogene (TGC to AGC). Out of 28 members who were at risk of MTC, 24 members participated in the screening test. 9 members tested positive for a mutation in the same chromosomal location as the index patient by PCR-RFLP. Basal serum calcitonins were above 100 pg/mL in 2 members. 3 members who had a RET point muatation but a normal basal serum calcitonin level participated in the pentagastrin stimulation test and the results were negative in all members. We found a small medullary thyroid carcinoma that had a diameter of 0.2 cm in a 16 years old boy according to a negative pentagastrin stimulation test and who had received a prophylactic total thyroidectomy. He had no evidence of a lymph node metastasis. CONCLUSION: We detected a germ-line mutation of the RET proto-oncogene in codon 618 of Exon 10 by a molecular genetic method in a family with a hereditary MTC and found 9 members that had a negative history of MTC but had a RET point mutation. There was a very small MTC found in a 16 years old boy who had a normal pentagastrin stimulation test result. Therefore, It is recommended that a prophylactic total thyroidectomy be performed as well as in members that have a mutation of the RET proto-oncogene because MTC can metastasize early in its disease course.'

Prevalence Thyroid Cancer in Patients with Cold Thyroid Nodules in Relation to Sex, Age, And Multinodularity.: Won Bae Kim, Hyun Kyung Chung, Chang Hoon Yim, Do Joon Park, Sung Yeon Kim, Bo Yeon Cho, Hong Gyu Lee; J Korean Endocr Soc. 1998;13(3):366-372. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We evaluated the prevalence of thyroid cancer in patients with cold thyroid nodules and the impact of sex, age, hardness of nodule, and multinodularity as factors able to predict the probability of malignancy in patients with nodular thyroid diseases. METHODS: We examined a 728 patients who visited Seoul National University Hospital with one or more cold thyroid nodules between Jan. 1996 and Dec. 1997. After clinical evaluations including medical history, physical examinations(size, hardness and multiplicity of nodule), fine needle aspiration biopsies and cytologic examinations were carried out. RESULTS: Among the 728 cases, 76 cases(10.4%) were diagnosed as cancer and 602 cases (82.6%) were diagnosed as benign nodule. The prevalence of cancer was significantly lower in female patients with cold nodules(9.4%, 62/662) than in males(17.5%, 11/63)(p=0.041). Age was an important factor in both sexes. The proportion of nodules that were malignant was lower in patients of 20-60 years old(8,9%, 56/632) than patients younger than 20 years old(1S.1%, 2/11) or older than 60 years old(18.3%, 15/82)(p=0.019). The prevalence of cancer was significantly higher in hard nodules(36.3%, 41/113) than firm(5.2%, 30/574) or soft nodules(5.3%, 2/38)(p= 0.001). There was no size difference between malignant(25.2 +- 13.7mm) and benign nodules(25.3 +- 8.9mm)(p=0.9425). The prevalence of thyroid cancer in solitary nodule(10.6%, 63/593) was not different from that in multiple nodules(7.6%, 10/132)(p=0.293). CONCLUSION: Our data suggest that thyroid nodules of the patients who are younger than 20 years old or older than 60 years old, male, as well as hard nodule require more careful evaluation for the risk of thyroid malignancies.

Usefulness of Immunoglobulin Fraction Precipitated with Polyethylene Glycol in Assay for TSH Receptor Antibodies using Chinese Hamster Overy Cells Expressing Human TSH Receptors.: Won Bae Kim, Hyun Kyung Chung, Chang Soon Koh, Chang Hoon Yim, Do Joon Park, Bo Yeon Cho, Hong Gyu Lee; J Korean Endocr Soc. 1998;13(2):167-180. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Graves' disease and primary myxedema are thought to be caused by the action of TSH receptor autoantibodies(thyroid stimulating antibody; TSAb & thyroid stimulation blocking antibody; TSBAb). Thus, detection of these antibodies is crucial in diagnosis and in follow up of those patients. Recently, a sensitive method using human TSH receptor transfected Chinese Hamster Ovary(CHO) cells has been developed. However, the complexity of IgG purification procedure is considered as a limitation for its clinical application as a routine test. The aim of this study is to determine whether polyethylene glycol(PEG)-precipitated immunogiobuIin fraction could substitute for purified IgG. METHODS: We developed optimal conditions for TSAb and TSBAb assays using crude, PEG precipitated immunoglobulin fraction; and evaluated the correlation of TSAb and TSBAb activities between thase measured using crude immunoglobulin fraction and purified IgG to clarify the usefulness of PEG-precipitated immunoglobulin fraction. TSH receptor expressing wild type CHO cells were used in TSAb and CHO cells expressing chimeric TSH receptor(Mc2; 90-165 amino acid residues were substituted by those of rat LH/CG receptar) were used in TSBAb assay to minimize the possible disturbing effects of TSAb in serum. RESULTS: The optimal serum amount for TSAb and TSBAb assay using PEG-precipitated immunoglobulin fraction were 250mL serum equivalent/well and 50mL serum equivalent/well, respectively. The optimal incubation time for both assays were 2 homs, and aptimal ccrncentration of bTSH for TSBAb assay was 0.1U/L. TSAb activities measured with PEG-precipitated immunoglobulin were significantly correlated with those measured with purified IgG in 26 patients with Graves diseases(r=0.93, p<0.001). Although TSBAb activities measured using PEG-precipitated imrnunoglobulin were conelated with those measured using purified IgG in 20 patients with primary myxedema(r=0.86, p<0.001), the positive rate in TSBAb assay using PEG-precipitated immunoglobulin was lower than that of usmg purified IgG(20% v.s. 65%) because of negative conversion of TSBAb activities in samples with weakly positive TSBAb activities measured using purified IgG. CONCLUSION: PEG-precipitated immunoglobulin fraction could be used instead of purified IgG in TSAb assay using hTSHR-tranasfected wild type CHO cells with equal sensitivity and specificity. This simple and practical TSAb assay using PEG-precipitated immunoglobulin in hTSHR-transfected CHO cells would be useful in clinica1 practiee.

Outcome of Surgery and Radiotherapy in Acromegaly.: Chan Soo Shin, Chang Hoon Yim, Hee Won Jung, Dae Hee Han, Do Joon Park, Hee Jin Kim, Yun Yong Lee, Kyung Soo Park, Il Han Kim, Sung Yeon Kim, Hong Gyu Lee; J Korean Endocr Soc. 1998;13(2):156-166. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The primary goal of therapy for acmmegaly is to reduce excess growth hormone (GH) secretion through surgical excision of pituitary adenoma and, in patients with large tumors, to debulk tumor mass and decompress adjacent structures. For the patients in whom surgery is contraindicated or has failed, radiotherapy should be considered. However, there was no analysis of the outcome folIowing the treatment of acromegly in Korea. METHODS: We retrospectively reviewed 128 patients who underwent surgical excision or radiotherapy for acromegaly and followed at our hospital between January 1980 and July 1997 to investigate the outcome of surgny and radiotherapy for acromegaly and to analyze preoperative and preradiotherapeutic parameters that predict a successful outcome of therapy. RESULTS: Pituitary adenomectomy was underwent to the 113 patients with acromegaly, then 33.6% of them showed basa1 GH levels below 5 ug/L and basal GH levels were dropped below 2.5 ug/L in 22.1% of the 113 patients. Postoperative basal GH levels were significantly correlated with preoperative tumor size(r=0.54, p<0.05) and preoperative GH levels(r=0.44, p<0.05). A successful outcome of surgery was influenced by preoperative tumor size, preoperative GH level and extrasellar extension. Multivariate analysis indicated that preoperative tumor size was an independent significant factor affecting the postoperative outcome(OR=2.19, p<0.05). After radiotherapy, the median years of decrease GH<10ug/L and <5ug/L were 3.7 and 7.8, respectively and GH levels of <5ug/L occurred in 35 percent of the patients at 5 years and in 56 percent at 10 yeats. The outcome of radiotherapy depends on the GH levels in preradiotherapy. CONCLUSION: The most reliable prognostic preoperative parameter of successful outcome of surgery was preoperative tumor size and the rate of fall in serum GH after radiotherapy is comparable to the preradiotherapy GH levels in our study, so that early diagnosis and proper treatment can improve the outcome of therapy in the patients with acromegaly. In the cases of large GH-secreting pituitary adenoma, it is required a combination of surgery and radiotherapy to achieve maximal suppresssion of GH levels before radiotherapy.

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