Endocrinology and Metabolism

Volume 35(4); December 2020

Review Articles

Thyroid
Tumor Cells and Cancer-Associated Fibroblasts: A Synergistic Crosstalk to Promote Thyroid Cancer: Laura Fozzatti, Sheue-yann Cheng; Endocrinol Metab. 2020;35(4):673-680. Published online November 9, 2020; DOI: https://doi.org/10.3803/EnM.2020.401

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258 Download
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Thyroid cancer is the most common endocrine malignancy. Although most thyroid cancer patients are successfully treated and have an excellent prognosis, a percentage of these patients will develop aggressive disease and, eventually, progress to anaplastic thyroid cancer. Since most patients with this type of aggressive thyroid carcinoma will die from the disease, new treatment strategies are urgently needed. Tumor cells live in a complex and dynamic tumor microenvironment composed of different types of stromal cells. Cancer-associated fibroblasts (CAFs) are one of the most important cell components in the tumor microenvironment of most solid tumors, including thyroid cancer. CAFs originate mainly from mesenchymal cells and resident fibroblasts that are activated and reprogrammed in response to paracrine factors and cytokines produced and released by tumor cells. Upon reprogramming, which is distinguished by the expression of different marker proteins, CAFs synthesize and secret soluble factors. The secretome of CAFs directly impacts different functions of tumor cells. This bi-directional interplay between CAFs and tumor cells within the tumor microenvironment ends up fostering tumor cancer progression. CAFs are therefore key regulators of tumor progression and represent an under-explored therapeutic target in thyroid cancer.

Citations

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Priscilla Guglielmo, Pierpaolo Alongi, Lucia Baratto, Miriam Conte, Elisabetta Maria Abenavoli, Ambra Buschiazzo, Greta Celesti, Francesco Dondi, Rossella Filice, Joana Gorica, Lorenzo Jonghi-Lavarini, Riccardo Laudicella, Maria Librando, Flavia Linguanti
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Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer
Ece Ozmen, Tevriz Dilan Demir, Gulnihal Ozcan
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Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy
Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C. Henderson, Maria Puche, Sayan Alekseev, Jocelynn G. Colunga-Minutti, Mark E. Zafereo, Stephen Y. Lai, Sang T. Kim, Maria E. Cabanillas, Roza Nurieva
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Fabio Volpe, Carmela Nappi, Emilia Zampella, Erica Di Donna, Simone Maurea, Alberto Cuocolo, Michele Klain
Current Oncology.2024; 31(7): 3870. CrossRef
New insights into the mechanisms of the extracellular matrix and its therapeutic potential in anaplastic thyroid carcinoma
Jinkun Xia, Yuyu Shi, Xinxu Chen
Scientific Reports.2024;[Epub] CrossRef
Improving the diagnostic strategy for thyroid nodules: a combination of artificial intelligence-based computer-aided diagnosis system and shear wave elastography
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Co-cultivation of human granulosa cells with ovarian cancer cells leads to a significant increase in progesterone production
Detlef Pietrowski, Martina Grgic, Isabella Haslinger, Julian Marschalek, Christian Schneeberger
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Secretome of Stromal Cancer-Associated Fibroblasts (CAFs): Relevance in Cancer
Deepshikha Mishra, Debabrata Banerjee
Cells.2023; 12(4): 628. CrossRef
Head-to-Head Comparison of [68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DOTANOC Positron Emission Tomography/Computed Tomography Imaging for the Follow-Up Surveillance of Patients with Medullary Thyroid Cancer
Sanjana Ballal, Madhav Prasad Yadav, Frank Roesch, Shobhana Raju, Swayamjeet Satapathy, Parvind Sheokand, Euy Sung Moon, Marcel Martin, Shipra Awarwal, Madhavi Tripathi, Chandrasekhar Bal
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Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers
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Identifying the cancer-associated fibroblast signature to predict the prognosis and immunotherapy response in patients with lung squamous cell carcinoma
Yinhui Zhu, Yingqun Zhu, Sirui Chen, Qian Cai
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Roles and new Insights of Macrophages in the Tumor Microenvironment of Thyroid Cancer
Qi Liu, Wei Sun, Hao Zhang
Frontiers in Pharmacology.2022;[Epub] CrossRef
Rab22a Promotes Epithelial-Mesenchymal Transition in Papillary Thyroid Carcinoma by Activating PI3K/AKT/mTOR Signaling Pathway
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Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
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The clinical significance of thyroid hormone-responsive in thyroid carcinoma and its potential regulatory pathway
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Thyroid Cancer and Fibroblasts
Angelica Avagliano, Giuseppe Fiume, Claudio Bellevicine, Giancarlo Troncone, Alessandro Venuta, Vittoria Acampora, Sabrina De Lella, Maria Rosaria Ruocco, Stefania Masone, Nunzio Velotti, Pietro Carotenuto, Massimo Mallardo, Carmen Caiazza, Stefania Monta
Cancers.2022; 14(17): 4172. CrossRef
TIM3 Expression in Anaplastic-Thyroid-Cancer-Infiltrating Macrophages: An Emerging Immunotherapeutic Target
Luz Maria Palacios, Victoria Peyret, María Estefania Viano, Romina Celeste Geysels, Yair Aron Chocobar, Ximena Volpini, Claudia Gabriela Pellizas, Juan Pablo Nicola, Claudia Cristina Motran, María Cecilia Rodriguez-Galan, Laura Fozzatti
Biology.2022; 11(11): 1609. CrossRef
Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma
Zhao-Shan Niu, Wen-Hong Wang, Xiao-Jun Niu
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Recent advances in regenerative medicine strategies for cancer treatment
Vahid Mansouri, Nima Beheshtizadeh, Maliheh Gharibshahian, Leila Sabouri, Mohammad Varzandeh, Nima Rezaei
Biomedicine & Pharmacotherapy.2021; 141: 111875. CrossRef
Secreted Factors by Anaplastic Thyroid Cancer Cells Induce Tumor-Promoting M2-like Macrophage Polarization through a TIM3-Dependent Mechanism
Cinthia Carolina Stempin, Romina Celeste Geysels, Sunmi Park, Luz Maria Palacios, Ximena Volpini, Claudia Cristina Motran, Eva Virginia Acosta Rodríguez, Juan Pablo Nicola, Sheue-yann Cheng, Claudia Gabriela Pellizas, Laura Fozzatti
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Novel Fibroblast Activation Protein Inhibitor-Based Targeted Theranostics for Radioiodine-Refractory Differentiated Thyroid Cancer Patients: A Pilot Study
Sanjana Ballal, Madhav Prasad Yadav, Euy Sung Moon, Frank Roesch, Samta Kumari, Shipra Agarwal, Madhavi Tripathi, Ranjit Kumar Sahoo, Bharadwaj Srinivas Mangu, Avinash Tupalli, Chandrasekhar Bal
Thyroid.2021;[Epub] CrossRef
Emerging Biomarkers in Thyroid Practice and Research
Shipra Agarwal, Andrey Bychkov, Chan-Kwon Jung
Cancers.2021; 14(1): 204. CrossRef

Obesity and Metabolism
Genetic and Environmental Factors Contributing to Visceral Adiposity in Asian Populations: Rachel Williams, Muthu Periasamy; Endocrinol Metab. 2020;35(4):681-695. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.772

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242 Download
34 Web of Science
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Abstract PDF PubReader ePub

Obesity-associated metabolic illnesses are increasing at an alarming rate in Asian countries. A common feature observed in the Asian population is a higher incidence of abdominal obesity—the “skinny-fat” Asian syndrome. In this review, we critically evaluate the relative roles of genetics and environmental factors on fat distribution in Asian populations. While there is an upward trend in obesity among most Asian countries, it appears particularly conspicuous in Malaysia. We propose a novel theory, the Malaysian gene-environment multiplier hypothesis, which explains how ancestral variations in feast-and-famine cycles contribute to inherited genetic predispositions that, when acted on by modern-day stressors—most notably, urbanization, westernization, lifestyle changes, dietary transitions, cultural pressures, and stress—contribute to increased visceral adiposity in Asian populations. At present, the major determinants contributing to visceral adiposity in Asians are far from conclusive, but we seek to highlight critical areas for further research.

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Thyroid
Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification: Yanhua Bai, Kennichi Kakudo, Chan Kwon Jung; Endocrinol Metab. 2020;35(4):696-715. Published online December 2, 2020; DOI: https://doi.org/10.3803/EnM.2020.807

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1,372 Download
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Advances in medical sciences and evidence-based medicine have led to momentous changes in classification and management of thyroid neoplasms. Much progress has been made toward avoiding overdiagnosis and overtreatment of thyroid cancers. The new 2017 World Health Organization (WHO) classification of thyroid neoplasms updated the diagnostic criteria and molecular and genetic characteristics reflecting the biology and behavior of the tumors, and newly introduced the category of borderline malignancy or uncertain malignant potential. Some neoplasms were subclassified, renamed, or redefined as a specific entity. This review introduces changes in the fourth edition WHO classification of thyroid tumors and updates the contemporary diagnosis and classification of thyroid tumors. We also discuss several challenges with the proposal of new diagnostic entities, since they have unique histopathologic and molecular features and clinical relevance.

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Miscellaneous
Sarcopenia and Muscle Aging: A Brief Overview: Tam Dao, Alexander E. Green, Yun A Kim, Sung-Jin Bae, Ki-Tae Ha, Karim Gariani, Mi-ra Lee, Keir J. Menzies, Dongryeol Ryu; Endocrinol Metab. 2020;35(4):716-732. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.405

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Abstract PDF PubReader ePub

The world is facing the new challenges of an aging population, and understanding the process of aging has therefore become one of the most important global concerns. Sarcopenia is a condition which is defined by the gradual loss of skeletal muscle mass and function with age. In research and clinical practice, sarcopenia is recognized as a component of geriatric disease and is a current target for drug development. In this review we define this condition and provide an overview of current therapeutic approaches. We further highlight recent findings that describe key pathophysiological phenotypes of this condition, including alterations in muscle fiber types, mitochondrial function, nicotinamide adenine dinucleotide (NAD⁺) metabolism, myokines, and gut microbiota, in aged muscle compared to young muscle or healthy aged muscle. The last part of this review examines new therapeutic avenues for promising treatment targets. There is still no accepted therapy for sarcopenia in humans. Here we provide a brief review of the current state of research derived from various mouse models or human samples that provide novel routes for the development of effective therapeutics to maintain muscle health during aging.

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Diabetes
In Vivo and In Vitro Quantification of Glucose Kinetics: From Bedside to Bench: Il-Young Kim, Sanghee Park, Yeongmin Kim, Yewon Chang, Cheol Soo Choi, Sang-Hoon Suh, Robert R. Wolfe; Endocrinol Metab. 2020;35(4):733-749. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.406

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Like other substrates, plasma glucose is in a dynamic state of constant turnover (i.e., rates of glucose appearance [R_a glucose] into and disappearance [R_d glucose] from the plasma) while staying within a narrow range of normal concentrations, a physiological priority. Persistent imbalance of glucose turnover leads to elevations (i.e., hyperglycemia, R_a>R_d) or falls (i.e., hypoglycemia, R_a<R_d) in the pool size, leading to clinical conditions such as diabetes. Endogenous Ra glucose is divided into hepatic glucose production via glycogenolysis and gluconeogenesis (GNG) and renal GNG. On the other hand, R_d glucose, the summed rate of glucose uptake by tissues/organs, involves various intracellular metabolic pathways including glycolysis, the tricarboxylic acid (TCA) cycle, and oxidation at varying rates depending on the metabolic status. Despite the dynamic nature of glucose metabolism, metabolic studies typically rely on measurements of static, snapshot information such as the abundance of mRNAs and proteins and (in)activation of implicated signaling networks without determining actual flux rates. In this review, we will discuss the importance of obtaining kinetic information, basic principles of stable isotope tracer methodology, calculations of in vivo glucose kinetics, and assessments of metabolic flux in experimental models in vivo and in vitro.

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Postabsorptive and postprandial glucose and fat metabolism in postmenopausal women with breast cancer—Preliminary data after chemotherapy compared to healthy controls
Kristian Buch-Larsen, Linn Gillberg, Haboon Ismail Ahmed, Simone Diedrichsen Marstrand, Michael Andersson, Gerrit van Hall, Charlotte Brøns, Peter Schwarz
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Yeongmin Kim, Sanghee Park, Jinseok Lee, Jiwoong Jang, Jiyeon Jung, Jin-Ho Koh, Cheol Soo Choi, Robert R. Wolfe, Il-Young Kim
Metabolites.2022; 12(1): 84. CrossRef
Exploring Human Muscle Dynamics In Vivo Using Stable Isotope Tracers
Il-Young Kim, Sanghee Park, Jiwoong Jang, Yeongmin Kim, Hee-Joo Kim
Annals of Clinical Nutrition and Metabolism.2022; 14(2): 40. CrossRef

Thyroid
Percutaneous Adrenal Radiofrequency Ablation: A Short Review for Endocrinologists: Byung Kwan Park; Endocrinol Metab. 2020;35(4):750-755. Published online December 2, 2020; DOI: https://doi.org/10.3803/EnM.2020.880

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Image-guided radiofrequency ablation (RFA) has been accepted as a minimally invasive treatment for adrenal tumors in patients who are unable to undergo adrenalectomy. Accordingly, this treatment has become more readily available for treating functioning or non-functioning adrenal masses. Thus, endocrinologists need a better understanding of percutaneous RFA of adrenal tumors. The purpose of this review is to briefly describe the basic mechanism of RFA, indications and contraindications, patient preparation prior to RFA, type of complications, how to avoid complications, RFA procedures, and treatment outcomes.

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Clinical Features and Etiology of Recurrent Hypertension after Adrenalectomy
Xilan Dong, Qianhui Ling, Jin Bian, Yuehua Li, Mengjia Chen, Sufang Hao, Wenjun Ma, Huimin Zhang, Jun Cai, Ying Lou
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Short-term outcome of adrenal radiofrequency ablation of adrenal cysts: a single-center experience
Shin Jeong Pak, Yu-mi Lee, Pyo Nyun Kim, Byung-Chang Kim, Jae Won Cho, Won Woong Kim, Tae-Yon Sung, Ki-wook Chung, Suck Joon Hong
Scientific Reports.2023;[Epub] CrossRef
Case report of trans-renal ablation procedures for a recurrent pheochromocytoma in von Hippel-Lindau disease
Byung Kwan Park
Precision and Future Medicine.2023; 7(2): 90. CrossRef
Efficacy and safety of radiofrequency ablation in the treatment of inoperable patients with pulmonary malignant nodules
Peng Qie, Xuejiao Xun, Xiaodong Nie, Qifan Yin, Hongshang Cui, Lijun Liu, Huien Wang
ANZ Journal of Surgery.2023; 93(12): 2969. 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
Minimally invasive techniques in benign and malignant adrenal tumors
Ahmet Bulent Dogrul, Omer Cennet, Anıl Hilmi Dincer
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Asian Conference on Tumor Ablation Guidelines for Adrenal Tumor Ablation
Byung Kwan Park, Masashi Fujimori, Shu-Huei Shen, Uei Pua
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The role and place of mini-invasive methods of local tumor destruction in adrenal gland surgery
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Miscellaneous
Coordination of Multiple Cellular Processes by NR5A1/Nr5a1: Ken-ichirou Morohashi, Miki Inoue, Takashi Baba; Endocrinol Metab. 2020;35(4):756-764. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.402

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The agenesis of the gonads and adrenal gland in revealed by knockout mouse studies strongly suggested a crucial role for Nr5a1 (SF-1 or Ad4BP) in organ development. In relation to these striking phenotypes, NR5A1/Nr5a1 has the potential to reprogram cells to steroidogenic cells, endow pluripotency, and regulate cell proliferation. However, due to limited knowledge regarding NR5A1 target genes, the mechanism by which NR5A1/Nr5a1 regulates these fundamental processes has remained unknown. Recently, newlyestablished technologies have enabled the identification of NR5A1 target genes related to multiple metabolic processes, as well as the aforementioned biological processes. Considering that active cellular processes are expected to be accompanied by active metabolism, NR5A1 may act as a key factor for processes such as cell differentiation, proliferation, and survival by coordinating these processes with cellular metabolism. A complete and definite picture of the cellular processes coordinated by NR5A1/Nr5a1 could be depicted by accumulating evidence of the potential target genes through whole genome studies.

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Development of sexual dimorphism of skeletal muscles through the adrenal cortex, caused by androgen-induced global gene suppression
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A novel heterozygous SF1/NR5A1 gene variant causes 46,XY DSD-gonadal dysgenesis with hypergonadotropic hypogonadism without adrenal insufficiency
Luis Ramos
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A conserved NR5A1-responsive enhancer regulates SRY in testis-determination
Denis Houzelstein, Caroline Eozenou, Carlos F. Lagos, Maëva Elzaiat, Joelle Bignon-Topalovic, Inma Gonzalez, Vincent Laville, Laurène Schlick, Somboon Wankanit, Prochi Madon, Jyotsna Kirtane, Arundhati Athalye, Federica Buonocore, Stéphanie Bigou, Gerard
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Role of NR5A1 Gene Mutations in Disorders of Sex Development: Molecular and Clinical Features
Giovanni Luppino, Malgorzata Wasniewska, Roberto Coco, Giorgia Pepe, Letteria Anna Morabito, Alessandra Li Pomi, Domenico Corica, Tommaso Aversa
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Induced pluripotent stem cell line generated from a patient with differences in sex development (DSD) and multiple genetic variants including a large deletion in NR5A1
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Adrenal gland
Embryonic Development and Adult Regeneration of the Adrenal Gland: Ji-Hoon Kim, Man Ho Choi; Endocrinol Metab. 2020;35(4):765-773. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.403

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The adrenal gland plays a pivotal role in an organism’s health span by controlling the endocrine system. Decades of research on the adrenal gland have provided multiscale insights into the development and maintenance of this essential organ. A particularly interesting finding is that founder stem/progenitor cells participate in adrenocortical development and enable the adult adrenal cortex to regenerate itself in response to hormonal stress and injury. Since major advances have been made in understanding the dynamics of the developmental process and the remarkable regenerative capacity of the adrenal gland, understanding the mechanisms underlying adrenal development, maintenance, and regeneration will be of interest to basic and clinical researchers. Here, we introduce the developmental processes of the adrenal gland and discuss current knowledge regarding stem/progenitor cells that regulate adrenal cortex remodeling and regeneration. This review will provide insights into the fascinating ongoing research on the development and regeneration of the adrenal cortex.

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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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Editorial

Thyroid
A High Frequency of Lobectomy Instead of Total Thyroidectomy to Treat Medullary Thyroid Cancer in Korea: Data from the Korean National Health Insurance Service: Sun Wook Cho; Endocrinol Metab. 2020;35(4):784-785. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.408

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Original Articles

Clinical Study
The Association of Overt and Subclinical Hyperthyroidism with the Risk of Cardiovascular Events and Cardiovascular Mortality: Meta-Analysis and Systematic Review of Cohort Studies: Seo Young Sohn, Eunyoung Lee, Min Kyung Lee, Jae Hyuk Lee; Endocrinol Metab. 2020;35(4):786-800. Published online November 25, 2020; DOI: https://doi.org/10.3803/EnM.2020.728

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Background
Whether hyperthyroidism is an independent risk factor for cardiovascular events remains controversial. We aimed to evaluate the association of overt and subclinical hyperthyroidism with the risk of ischemic heart disease (IHD), stroke, heart failure, and cardiovascular mortality.
Methods
Studies regarding the association between hyperthyroidism and cardiovascular events were searched on PubMed and Embase databases. The cardiovascular disease (CVD) risk was classified as high and low, based on pre-existing diseases, including history of coronary, cerebral, or peripheral artery disease; heart failure; atrial fibrillation; diabetes mellitus; or chronic kidney disease.
Results
Thirty-seven cohort studies were included in this meta-analysis. The pooled hazard ratio for subjects with overt hyperthyroidism compared with the control group was 1.11 (95% confidence interval [CI], 1.03 to 1.19) for IHD, 1.35 (95% CI, 1.03 to 1.75) for stroke, and 1.20 (95% CI, 1.00 to 1.46) for cardiovascular mortality. For subjects with subclinical hyperthyroidism, the pooled hazard ratio was 1.24 (95% CI, 1.07 to 1.45) for IHD, when compared with the control group. Subgroup analysis by CVD risk showed that the risk of stroke in overt hyperthyroidism was increased in the low CVD risk group; however, these association was not observed in the high CVD risk group. Similarly, the risk of IHD in subjects with subclinical hyperthyroidism was significantly increased in the low CVD risk group.
Conclusion
Overt hyperthyroidism is associated with increased risk of IHD, stroke, and cardiovascular mortality, and subclinical hyperthyroidism is associated with increased risk of IHD. These associations were particularly observed in the low risk CVD group without underlying CVD.

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Clinical Study
Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults: Sung Hye Kong, Ji Won Yoon, Jung Hee Kim, JooYong Park, Jiyeob Choi, Ji Hyun Lee, A Ram Hong, Nam H. Cho, Chan Soo Shin; Endocrinol Metab. 2020;35(4):801-810. Published online November 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.735

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Background
As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS).
Methods
TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers.
Results
In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=–0.0281, β=–0.0465, respectively).
Conclusion
In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.

Citations

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A novel genetic mouse model of osteoporosis with double heterozygosity of Irx3 and Irx5 characterizes sex-dependent phenotypes in bone homeostasis
Xinyu Chen, Zhengchao Dou, Joe Eun Son, Meng Duan, Fei Yang, Shankuan Zhu, Chi-Chung Hui
Bone.2025; 190: 117282. CrossRef
Neural EGFL like 1 as a novel gene for Trabecular Bone Score in older adults: The Bushehr Elderly Health (BEH) program
Mohammad Bidkhori, Mahdi Akbarzadeh, Noushin Fahimfar, Mina Jahangiri, Sahar Seddiq, Bagher Larijani, Iraj Nabipour, Mahsa Mohammad Amoli, Nekoo Panahi, Abbas Dehghan, Kourosh Holakouie-Naieni, Afshin Ostovar, Dengshun Miao
PLOS ONE.2024; 19(9): e0309401. CrossRef

Clinical Study
Trends in the Diagnosis and Treatment of Patients with Medullary Thyroid Carcinoma in Korea: Hwa Young Ahn, Jae Eun Chae, Hyemi Moon, Junghyun Noh, Young Joo Park, Sin Gon Kim; Endocrinol Metab. 2020;35(4):811-819. Published online November 20, 2020; DOI: https://doi.org/10.3803/EnM.2020.709

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Background
Thyroid cancer is becoming increasingly common worldwide, but little is known about the epidemiology of medullary thyroid carcinoma (MTC). This study investigated the current status of the incidence and treatment of MTC using Korean National Health Insurance Service (NHIS) data for the entire Korean population from 2004 to 2016.
Methods
This study included 1,790 MTC patients identified from the NHIS database.
Results
The age-standardized incidence rate showed a slightly decreasing or stationary trend during the period, from 0.25 per 100,000 persons in 2004 to 0.19 in 2016. The average proportion of MTC among all thyroid cancers was 0.5%. For initial surgical treatment, 65.4% of patients underwent total thyroidectomy. After surgery, external-beam radiation therapy (EBRT) was performed in 10% of patients, a proportion that increased from 6.7% in 2004 to 11.0% in 2016. Reoperations were performed in 2.7% of patients (n=49) at a median of 1.9 years of follow-up (interquartile range, 1.2 to 3.4). Since November 2015, 25 (1.4%) patients with MTC were prescribed vandetanib by December 2016.
Conclusion
The incidence of MTC decreased slightly with time, and the proportion of patients who underwent total thyroidectomy was about 65%. EBRT, reoperation, and tyrosine kinase inhibitor therapy are additional treatments after initial surgery for advanced MTC in Korea.

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Endocrinology and Metabolism.2020; 35(4): 784. CrossRef

Clinical Study
Insulin Secretion and Insulin Resistance Trajectories over 1 Year after Kidney Transplantation: A Multicenter Prospective Cohort Study: Jun Bae Bang, Chang-Kwon Oh, Yu Seun Kim, Sung Hoon Kim, Hee Chul Yu, Chan-Duck Kim, Man Ki Ju, Byung Jun So, Sang Ho Lee, Sang Youb Han, Cheol Woong Jung, Joong Kyung Kim, Su Hyung Lee, Ja Young Jeon; Endocrinol Metab. 2020;35(4):820-829. Published online November 18, 2020; DOI: https://doi.org/10.3803/EnM.2020.743

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Background
We investigated the changing patterns of insulin secretion and resistance and risk factors contributing to the development of post-transplant diabetes mellitus (PTDM) in kidney recipients under tacrolimus-based immunosuppression regimen during 1 year after transplantation.
Methods
This was a multicenter prospective cohort study. Of the 168 subjects enrolled in this study, we analyzed a total 87 kidney transplant recipients without diabetes which was assessed by oral glucose tolerance test before transplantation. We evaluated the incidence of PTDM and followed up the index of insulin secretion (insulinogenic index [IGI]) and resistance (homeostatic model assessment for insulin resistance [HOMA-IR]) at 3, 6, 9 months, and 1 year after transplantation by oral glucose tolerance test and diabetes treatment. We also assessed the risk factors for incident PTDM.
Results
PTDM developed in 23 of 87 subjects (26.4%) during 1 year after transplantation. More than half of total PTDM (56.5%) occurred in the first 3 months after transplantation. During 1 year after transplantation, insulin resistance (HOMA-IR) was increased in both PTDM and no PTDM group. In no PTDM group, the increase in insulin secretory function to overcome insulin resistance was also observed. However, PTDM group showed no increase in insulin secretion function (IGI). Old age, status of prediabetes and episode of acute rejection were significantly associated with the development of PTDM.
Conclusion
In tacrolimus-based immunosuppressive drugs regimen, impaired insulin secretory function for reduced insulin sensitivity contributed to the development of PTDM than insulin resistance during 1 year after transplantation.

Citations

Citations to this article as recorded by

Prevalence of new-onset diabetes mellitus after kidney transplantation: a systematic review and meta-analysis
Qiufeng Du, Tao Li, Xiaodong Yi, Shuang Song, Jing Kang, Yunlan Jiang
Acta Diabetologica.2024; 61(7): 809. CrossRef
Normalization of impaired glucose tolerance after kidney transplantation is associated with improved β-cell function
Maiko Miyamoto, Akinobu Nakamura, Aika Miya, Hiroshi Nomoto, Hiraku Kameda, Kyu Yong Cho, Naoya Iwahara, Kiyohiko Hotta, Nobuo Shinohara, Tatsuya Atsumi
American Journal of Physiology-Endocrinology and Metabolism.2024; 327(2): E194. CrossRef
Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal
Lourdes Balcázar-Hernández, Victoria Mendoza-Zubieta, Baldomero González-Virla, Brenda González-García, Mariana Osorio-Olvera, Jesús Ubaldo Peñaloza-Juarez, Irene Irisson-Mora, Martha Cruz-López, Raúl Rodríguez-Gómez, Ramón Espinoza-Pérez, Guadalupe Varga
Brazilian Journal of Nephrology.2023; 45(1): 77. CrossRef
Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients
Lourdes Balcázar-Hernández, Victoria Mendoza-Zubieta, Baldomero González-Virla, Brenda González-García, Mariana Osorio-Olvera, Jesús Ubaldo Peñaloza-Juarez, Irene Irisson-Mora, Martha Cruz-López, Raúl Rodríguez-Gómez, Ramón Espinoza-Pérez, Guadalupe Varga
Brazilian Journal of Nephrology.2023; 45(1): 77. CrossRef
Postoperative fasting plasma glucose and family history diabetes mellitus can predict post-transplantation diabetes mellitus in kidney transplant recipients
Le Wang, Jin Huang, Yajuan Li, Kewei Shi, Sai Gao, Wangcheng Zhao, Shanshan Zhang, Chenguang Ding, Wei Gao
Endocrine.2023; 81(1): 58. CrossRef
Changes in glucose metabolism among recipients with diabetes 1 year after kidney transplant: a multicenter 1-year prospective study
Jun Bae Bang, Chang-Kwon Oh, Yu Seun Kim, Sung Hoon Kim, Hee Chul Yu, Chan-Duck Kim, Man Ki Ju, Byung Jun So, Sang Ho Lee, Sang Youb Han, Cheol Woong Jung, Joong Kyung Kim, Hyung Joon Ahn, Su Hyung Lee, Ja Young Jeon
Frontiers in Endocrinology.2023;[Epub] CrossRef
Pretransplant evaluation and the risk of glucose metabolic alterations after renal transplantation: a prospective study
Arminda Fariña-Hernández, Domingo Marrero-Miranda, Estefania Perez-Carreño, Antonia De Vera-Gonzalez, Alejandra González, Cristian Acosta-Sorensen, Ana Elena Rodríguez-Rodríguez, Tatiana Collantes, Marta del Pino García, Ana Isabel Rodríguez-Muñoz, Carla
Nephrology Dialysis Transplantation.2022;[Epub] CrossRef

Clinical Study
Clinical Outcomes after Early and Delayed Radioiodine Remnant Ablation in Patients with Low-Risk Papillary Thyroid Carcinoma: Propensity Score Matching Analysis: Jonghwa Ahn, Meihua Jin, Eyun Song, Min Ji Jeon, Tae Yong Kim, Jin-Sook Ryu, Won Bae Kim, Young Kee Shong, Ji Min Han, Won Gu Kim; Endocrinol Metab. 2020;35(4):830-837. Published online November 18, 2020; DOI: https://doi.org/10.3803/EnM.2020.747

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Background
The clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC.
Methods
We included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (<90 days) and the delayed (≥90 days) RRA groups based on the interval between TT and RRA. The results of diagnostic whole-body scan (DxWBS), ongoing risk stratification (ORS; response to therapy), and disease-free survival (DFS) were evaluated before and after propensity score matching (PSM).
Results
Among the 526 patients, 75 (14.3%) patients underwent delayed RRA; they had more cervical lymph node metastasis and received a higher RRA dose than those who underwent early RRA. The median follow-up period was 9.1 years after initial therapy, and the structural recurrence rate was 1.9%. In DxWBS, 60 patients had focal iodine uptake limited in operative bed, with no significant difference between groups. According to ORS, 78%, 20%, 1%, and 1% patients were classified into excellent, indeterminate, biochemical incomplete, and structural incomplete response groups, respectively. There was no significant difference in ORS or DFS between groups before and after PSM.
Conclusion
The timing of the first RRA had no clinical impact in patients with low-risk PTC. Thus, the clinical decision for RRA can be determined >3 months after TT considering other prognostic factors.

Citations

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Dynamic risk assessment in patients with differentiated thyroid cancer
Erika Abelleira, Fernando Jerkovich
Reviews in Endocrine and Metabolic Disorders.2024; 25(1): 79. CrossRef
Ablation Rates and Long-Term Outcome Following Low-Dose Radioiodine for Differentiated Thyroid Cancer in the West of Scotland: A Retrospective Analysis
Kathryn Graham, Fay Tough, Helena Belikova, Irene Wotherspoon, David Colville, Nicholas Reed
Endocrine Practice.2024; 30(4): 327. CrossRef
Radioiodine ablation after thyroidectomy could be safely abandoned or postponed in selected stage I papillary thyroid carcinoma patients of low-risk group: an observational prospective study
S.M. Cherenko, A.Yu. Glagolieva, D.E. Makhmudov
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2024; 20(1): 7. CrossRef
Analysis of delayed initial radioactive iodine therapy and clinical outcomes in papillary thyroid cancer: a two-center retrospective study
Tao He, Ming Li, Zheng-lian Gao, Xiang-yu Li, Hai-rong Zhong, Cui-shuang Ding, Hua-wei Cai
Nuclear Medicine Communications.2024; 45(9): 779. CrossRef
Advances in the selection and timing of postoperative radioiodine treatment in patients with differentiated thyroid carcinoma
Xin Dai, Xinyi Ren, Jinyu Zhang, Yuxin Zheng, Zhengjie Wang, Gang Cheng
Annals of Nuclear Medicine.2024; 38(9): 688. CrossRef
Comparative evaluation of low and high radioiodine doses in differentiated thyroid carcinoma management: A multicenter study
M.B. Al-Osaimi, E.M. Abdelrazek, Ehab M. Attalla, Hosam Salaheldin
Journal of Radiation Research and Applied Sciences.2024; 17(4): 101206. CrossRef
Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK
J. Wadsley, N. Armstrong, V. Bassett-Smith, M. Beasley, R. Chandler, L. Cluny, A.J. Craig, K. Farnell, K. Garcez, N. Garnham, K. Graham, A. Hallam, S. Hill, H. Hobrough, F. McKiddie, M.W.J. Strachan
Clinical Oncology.2023; 35(1): 42. CrossRef
Delay of initial radioactive iodine therapy beyond 3 months has no effect on clinical responses and overall survival in patients with thyroid carcinoma: A cohort study and a meta‐analysis
Fang Cheng, Juan Xiao, Fengyan Huang, Chunchun Shao, Shouluan Ding, Canhua Yun, Hongying Jia
Cancer Medicine.2022; 11(12): 2386. CrossRef
Delayed (>3 Months) Postoperative Radioactive Iodine Ablation Does Not Impact Clinical Response or Survival in Differentiated Thyroid Cancers
Tatiana Fedorova, Lilah F. Morris-Wiseman
Clinical Thyroidology.2022; 34(10): 456. CrossRef

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