Endocrinology and Metabolism

Original Articles

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

Hypothalamus and pituitary gland
Genetic Landscape and Clinical Manifestations of Multiple Endocrine Neoplasia Type 1 in a Korean Cohort: A Multicenter Retrospective Analysis: Boram Kim, Seung Hun Lee, Chang Ho Ahn, Han Na Jang, Sung Im Cho, Jee-Soo Lee, Yu-Mi Lee, Su-Jin Kim, Tae-Yon Sung, Kyu Eun Lee, Woochang Lee, Jung-Min Koh, Moon-Woo Seong, Jung Hee Kim; Endocrinol Metab. 2024;39(6):956-964. Published online November 18, 2024; DOI: https://doi.org/10.3803/EnM.2024.2008

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

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

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

Adrenal gland
The Modified S-GRAS Scoring System for Prognosis in Korean with Adrenocortical Carcinoma: Sun Kyung Baek, Seung Hun Lee, Seung Shin Park, Chang Ho Ahn, Sung Hye Kong, Won Woong Kim, Yu-Mi Lee, Su Jin Kim, Dong Eun Song, Tae-Yon Sung, Kyu Eun Lee, Jung Hee Kim, Kyeong Cheon Jung, Jung-Min Koh; Endocrinol Metab. 2024;39(5):803-812. Published online September 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.2086

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Abstract PDF Supplementary Material PubReader ePub: Background
Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients.
Methods
Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0–1, 2–3, 4–5, and 6–9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell’s concordance index (C-index), and the Kaplan–Meier method.
Results
Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13).
Conclusion
mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.

Thyroid
BRAF^V600E Mutation Enhances Estrogen-Induced Metastatic Potential of Thyroid Cancer by Regulating the Expression of Estrogen Receptors: Minjun Kim, Su-jin Kim, Seong Yun Ha, Zhen Xu, Youngjin Han, Hyeon-Gun Jee, Sun Wook Cho, Young Joo Park, Kyu Eun Lee; Endocrinol Metab. 2022;37(6):879-890. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1563

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Background
Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAF^V600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAF^V600E on the estrogen-induced increase in metastatic potential in thyroid cancer.
Methods
Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAF^V600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAF^V600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data.
Results
Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAF^V600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAF^V600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis.
Conclusion
Our data show that BRAF^V600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAF^V600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

Citations

Citations to this article as recorded by

The importance of protein domain mutations in cancer therapy
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Heliyon.2024; 10(6): e27655. CrossRef
Three cases of thyroid cancer in transgender female veterans receiving gender-affirming estrogen treatment
John D. Christensen, Hiba T. Basheer
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Thyroid Cancer Prevalence, Risk Exposure, and Clinical Features Among Transgender Female Veterans
John David Christensen, Hiba T Basheer, Jose Joaquin Lado Abeal
Journal of the Endocrine Society.2024;[Epub] CrossRef
A review of complex hormone regulation in thyroid cancer: novel insights beyond the hypothalamus–pituitary–thyroid axis
Liu-han Chen, Tao Xie, Qian Lei, Yan-rui Gu, Chuan-zheng Sun
Frontiers in Endocrinology.2024;[Epub] CrossRef
Genes Co-Expressed with ESR2 Influence Clinical Outcomes in Cancer Patients: TCGA Data Analysis
Julia Maria Lipowicz, Agnieszka Malińska, Michał Nowicki, Agnieszka Anna Rawłuszko-Wieczorek
International Journal of Molecular Sciences.2024; 25(16): 8707. CrossRef
Preoperative Diagnosis of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma
瑜瑜叶
Advances in Clinical Medicine.2024; 14(12): 1036. CrossRef
Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer
Farzana Jasmine, Briseis Aschebrook-Kilfoy, Mohammad M. Rahman, Garrett Zaagman, Raymon H. Grogan, Mohammed Kamal, Habibul Ahsan, Muhammad G. Kibriya
Current Oncology.2023; 30(3): 2978. CrossRef
Editorial: Recent advances in papillary thyroid carcinoma: Progression, treatment and survival predictors
Erivelto Martinho Volpi, Margarita Carmen Ramirez-Ortega, Jose Federico Carrillo
Frontiers in Endocrinology.2023;[Epub] CrossRef

Adrenal Gland
Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism: Jung Hee Kim, Chang Ho Ahn, Su Jin Kim, Kyu Eun Lee, Jong Woo Kim, Hyun-Ki Yoon, Yu-Mi Lee, Tae-Yon Sung, Sang Wan Kim, Chan Soo Shin, Jung-Min Koh, Seung Hun Lee; Endocrinol Metab. 2022;37(2):369-382. Published online April 14, 2022; DOI: https://doi.org/10.3803/EnM.2022.1391

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Background
Optimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision- making before engaging in AVS and surgery in clinical practice.
Methods
We conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression.
Results
We developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index <25 kg/m2 (area under the curve, 0.819; 95% confidence interval, 0.774 to 0.865; sensitivity, 97.6%; specificity, 25.5%). In study B, we identified female, hypertension duration <5 years, anti-hypertension medication <2.5 daily defined dose, and the absence of coronary artery disease as predictors of clinical success, using stepwise logistic regression models (sensitivity, 94.2%; specificity, 49.3%). We validated our algorithm in the independent validation dataset (n=53).
Conclusion
We propose this new outcome-driven diagnostic algorithm, simultaneously considering unilateral aldosterone excess and clinical surgical benefits in PA patients.

Citations

Citations to this article as recorded by

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort
Jun Yang, Jacopo Burrello, Jessica Goi, Martin Reincke, Christian Adolf, Evelyn Asbach, Denise Brűdgam, Qifu Li, Ying Song, Jinbo Hu, Shumin Yang, Fumitoshi Satoh, Yoshikiyo Ono, Renata Libianto, Michael Stowasser, Nanfang Li, Qing Zhu, Namki Hong, Drishy
The Lancet Diabetes & Endocrinology.2025; 13(2): 119. CrossRef
Bridging Global and Local Perspectives on Primary Aldosteronism
Ohk-Hyun Ryu
Endocrinology and Metabolism.2025; 40(2): 195. CrossRef
Subtype-specific Body Composition and Metabolic Risk in Patients With Primary Aldosteronism
Seung Shin Park, Chang Ho Ahn, Sang Wan Kim, Ji Won Yoon, Jung Hee Kim
The Journal of Clinical Endocrinology & Metabolism.2024; 109(2): e788. CrossRef
Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes
Chang Ho Ahn, You-Bin Lee, Jae Hyeon Kim, Young Lyun Oh, Jung Hee Kim, Kyeong Cheon Jung
The Journal of Clinical Endocrinology & Metabolism.2024; 109(8): e1582. CrossRef
Predicting the resolution of hypertension following adrenalectomy in primary aldosteronism: Controversies and unresolved issues a narrative review
Luigi Marzano
Langenbeck's Archives of Surgery.2024;[Epub] CrossRef
Prognostic models to predict complete resolution of hypertension after adrenalectomy in primary aldosteronism: A systematic review and meta‐analysis
Luigi Marzano, Amir Kazory, Faeq Husain‐Syed, Claudio Ronco
Clinical Endocrinology.2023; 99(1): 17. CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
Endocrinology and Metabolism.2023; 38(6): 597. CrossRef

Adrenal Gland
Clinical and Molecular Characteristics of PRKACA L206R Mutant Cortisol-Producing Adenomas in Korean Patients: Insoon Jang, Su-jin Kim, Ra-Young Song, Kwangsoo Kim, Seongmin Choi, Jang-Seok Lee, Min-Kyeong Gwon, Moon Woo Seong, Kyu Eun Lee, Jung Hee Kim; Endocrinol Metab. 2021;36(6):1287-1297. Published online December 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.1217

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Abstract PDF Supplementary Material PubReader ePub: Background
An activating mutation (c.617A>C/p.Lys206Arg, L206R) in protein kinase cAMP-activated catalytic subunit alpha (PRKACA) has been reported in 35% to 65% of cases of cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and transcriptome analysis between PRKACA L206R mutants and wild-type CPAs in Korea.
Methods
We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh-frozen tumor tissues.
Results
The prevalence of the PRKACA L206R mutation was 51% (29/57). The mean age of the study subjects was 42±12 years, and 87.7% (50/57) of the patients were female. Subjects with PRKACA L206R mutant CPAs showed smaller adenoma size (3.3±0.7 cm vs. 3.8±1.2 cm, P=0.059) and lower dehydroepiandrosterone sulfate levels (218±180 ng/mL vs. 1,511±3,307 ng/mL, P=0.001) than those with PRKACA wild-type CPAs. Transcriptome profiling identified 244 differentially expressed genes (DEGs) between PRKACA L206R mutant (n=8) and wild-type CPAs (n=5), including five upregulated and 239 downregulated genes in PRKACA L206R mutant CPAs (|fold change| ≥2, P<0.05). Among the upstream regulators of DEGs, CTNNB1 was the most significant transcription regulator. In several pathway analyses, the Wnt signaling pathway was downregulated and the steroid biosynthesis pathway was upregulated in PRKACA mutants. Protein-protein interaction analysis also showed that PRKACA downregulates Wnt signaling and upregulates steroid biosynthesis.
Conclusion
The PRKACA L206R mutation in CPAs causes high hormonal activity with a limited proliferative capacity, as supported by transcriptome profiling.

Thyroid
Association between Iodine Intake, Thyroid Function, and Papillary Thyroid Cancer: A Case-Control Study: Kyungsik Kim, Sun Wook Cho, Young Joo Park, Kyu Eun Lee, Dong-Wook Lee, Sue K. Park; Endocrinol Metab. 2021;36(4):790-799. Published online August 11, 2021; DOI: https://doi.org/10.3803/EnM.2021.1034

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Background
This study aimed to assess the effects of iodine intake, thyroid function, and their combined effect on the risk of papillary thyroid cancer (PTC) and papillary thyroid microcarcinoma (PTMC).
Methods
A case-control study was conducted including 500 community-based controls who had undergone a health check-up, and 446 overall PTC cases (209 PTC and 237 PTMC) from the Thyroid Cancer Longitudinal Study. Urinary iodine concentration (UIC), was used as an indicator of iodine intake, and serum for thyroid function. The risk of PTC and PTMC was estimated using unconditional logistic regression.
Results
Excessive iodine intake (UIC ≥220 μg/gCr) was associated with both PTC (odds ratio [OR], 18.13 95% confidence interval [CI], 8.87 to 37.04) and PTMC (OR, 8.02; 95% CI, 4.64 to 13.87), compared to adequate iodine intake (UIC, 85 to 219 μg/gCr). Free thyroxine (T4) levels ≥1.25 ng/dL were associated with PTC (OR, 1.97; 95% CI, 1.36 to 2.87) and PTMC (OR, 2.98; 95% CI, 2.01 to 4.41), compared to free T4 levels of 0.7 to 1.24 ng/dL. Individuals with excessive iodine intake and high free T4 levels had a greatly increased OR of PTC (OR, 43.48; 95% CI, 12.63 to 149.62), and PTMC (OR, 26.96; 95% CI, 10.26 to 70.89), compared to individuals with adequate iodine intake and low free T4 levels.
Conclusion
Excessive iodine intake using creatinine-adjusted UIC and high free T4 levels may have a synergistic effect on PTC and PTMC. Considering both iodine intake and thyroid function is important to assess PTC and PTMC risk.

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Continued rise in the incidence of thyroid cancer in Iran: true increase or overdiagnosis?
Mahnaz Pejman Sani, Shahrzad Mohseni, Hilda Samimi, Shirzad Nasiri, Babak Fallahi, Mohammadreza Mohajeri-Tehrani, Seyed Mohammad Tavangar, Mahmood Naderi, Nooshin Shirzad, Bagher Larijani, Sayed Mahmoud Sajjadi-Jazi, Gholamreza Roshandel, Vahid Haghpanah
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Iodine Excess Is Associated with Thyroid Dysfunction Among the Elderly
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Biological Trace Element Research.2024;[Epub] CrossRef
Association between urinary iodine concentration and the risk of papillary thyroid cancer by sex and age: a case–control study
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Nomogram Model Based on Iodine Nutrition and Clinical Characteristics of Papillary Thyroid Carcinoma to Predict Lateral Lymph Node Metastasis
Junrong Wang, Yuzhang Gao, Yuxuan Zong, Weitong Gao, Xueying Wang, Ji Sun, Susheng Miao
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Content of Copper, Iron, Iodine, Rubidium, Strontium and Zinc in Thyroid Malignant Nodules and Thyroid Tissue adjacent to Nodules
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Distinguish Thyroid Malignant from Benign Alterations using Trace Element Contents in Nodular Tissue determined by Neutron Activation and Inductively Coupled Plasma Mass Spectrometry
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Seaweed and Iodine Intakes and SLC5A5 rs77277498 in Relation to Thyroid Cancer
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Iodine nutrition and papillary thyroid cancer
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Clinical Study
Efficacy of Intraoperative Neuromonitoring in Reoperation for Recurrent Thyroid Cancer Patients: Jang-il Kim, Su-jin Kim, Zhen Xu, JungHak Kwak, Jong-hyuk Ahn, Hyeong Won Yu, Young Jun Chai, June Young Choi, Kyu Eun Lee; Endocrinol Metab. 2020;35(4):918-924. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.778

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Background
The use of intraoperative neuromonitoring (IONM) in thyroid surgery to preserve recurrent laryngeal nerve (RLN) function has been widely accepted. We aimed to evaluate the usefulness of IONM in reoperation for recurrent thyroid cancer patients to help identify the RLN and prevent vocal cord palsy (VCP).
Methods
We analyzed 121 consecutive patients (with IONM group, 48 patients; without IONM group, 73 patients) who underwent reoperation for recurrent thyroid cancer after total thyroidectomy from January 2009 to March 2019 in our institution without VCP due to previous operations. Data including age, sex, number of previous operations, histologic subtype of the malignancy at the initial operation, operation time, RLNs at risk, difficulty of RLN identification, surgical procedure, VCP, and other postoperative complications were reviewed. Vocal cord movement evaluations were performed preoperatively and at 2 weeks postoperatively to evaluate RLN function. In patients with VCP, additional evaluations were performed. VCP exceeding 12 months after surgery was considered permanent VCP.
Results
VCP was observed in six (12.5%) and 16 (21.9%) patients with and without IONM (P=0.189). Transient and permanent VCP were found in three (6.3%) and three (6.3%) patients with IONM (P=0.098 and P=0.982, respectively) versus in 12 (16.4%) and four (5.5%) patients without IONM.
Conclusion
The incidence of transient VCP seems to be lower in reoperations with IONM; however, there was no statistical significances. Further study will be needed to ascertain the efficacy of IONM in reoperation for recurrent thyroid cancer patients.

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Updates in Surgery.2023; 75(4): 987. CrossRef
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Medicine.2021; 100(51): e28233. CrossRef

Clinical Study
Whole Exome Sequencing Identifies Novel Genetic Alterations in Patients with Pheochromocytoma/Paraganglioma: Soo Hyun Seo, Jung Hee Kim, Man Jin Kim, Sung Im Cho, Su Jin Kim, Hyein Kang, Chan Soo Shin, Sung Sup Park, Kyu Eun Lee, Moon-Woo Seong; Endocrinol Metab. 2020;35(4):909-917. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.756

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Background
Pheochromocytoma and paragangliomas (PPGL) are known as tumors with the highest level of heritability, approximately 30% of all cases. Clinical practice guidelines of PPGL recommend genetic testing for germline variants in all patients. In this study, we used whole exome sequencing to identify novel causative variants associated with PPGL to improve the detection of rare genetic variants in our cohort.
Methods
Thirty-six tested negative for pathogenic variants in previous Sanger sequencing or targeted gene panel testing for PPGL underwent whole exome sequencing. Whole exome sequencing was performed using DNA samples enriched using TruSeq Custom Enrichment Kit and sequenced with MiSeq (Illumina Inc.). Sequencing alignment and variant calling were performed using SAMtools.
Results
Among previously mutation undetected 36 patients, two likely pathogenic variants and 13 variants of uncertain significance (VUS) were detected in 32 pheochromocytoma-related genes. SDHA c.778G>A (p.Gly260Arg) was detected in a patient with head and neck paraganglioma, and KIF1B c.2787-2A>C in a patient with a bladder paraganglioma. Additionally, a likely pathogenic variant in BRCA2, VUS in TP53, and VUS in NFU1 were detected.
Conclusion
Exome sequencing further identified genetic alterations by 5.6% in previously mutation undetected patients in PPGL. Implementation of targeted gene sequencing consisted of extended genes of PPGL in routine clinical screening can support the level of comprehensive patient assessment.

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Review Article

Adrenal gland
Minimally Invasive Adrenal Surgery: JungHak Kwak, Kyu Eun Lee; Endocrinol Metab. 2020;35(4):774-783. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.404

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Since the introduction of minimally invasive surgery, laparoscopic adrenalectomy has become the main treatment option for adrenal masses. Various studies have reported that laparoscopic adrenalectomy showed fewer postoperative complications and faster recovery than conventional open adrenalectomy. Laparoscopic adrenalectomy can be performed through either the transperitoneal approach or the retroperitoneoscopic approach, which are widely used in most adrenal surgical procedures. Furthermore, with the development of minimally invasive surgery, organ-sparing adrenalectomy has recently emerged as a way to conserve functional adrenal gland tissue. According to recent data, organ-sparing adrenalectomy shows promising surgical, functional, and oncological outcomes including less intraoperative blood loss, maintenance of adrenal function, and low recurrence. Partial adrenalectomy was initially proposed for bilateral adrenal tumors in patients with hereditary disease to avoid chronic adrenal insufficiency. However, it has also gained popularity for the treatment of unilateral adrenal disease involving a small adrenal tumor because even patients with a unilateral adrenal gland may develop adrenal insufficiency in stressful situations. Therefore, partial adrenalectomy has become increasingly common to avoid lifelong steroid replacement and recurrence in most cases, especially in bilateral adrenal disease. This review article evaluates the current evidence on minimally invasive adrenalectomy and organ-preserving partial adrenalectomy.

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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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Letter

Adrenal gland
An Ectopic Cortisol-Producing Adrenocortical Adenoma Masquerading as a Liposarcoma in the Pararenal Space: Sunyoung Kang, Seung Shin Park, Jae Hyun Bae, Kyu Eun Lee, Jung Hee Kim, Chan Soo Shin; Endocrinol Metab. 2018;33(3):423-424. Published online August 14, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.423

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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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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.

Citations

Citations to this article as recorded by

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