Endocrinology and Metabolism

Namgok Lecture 2025

Current Knowledge on Atypical Parathyroid Tumors and Emerging Strategies for Risk Stratification: Hye-Sun Park, Milim Kim, Jong Ju Jeong, Namki Hong, Yumie Rhee; Received December 9, 2025 Accepted December 12, 2025 Published online January 7, 2026; DOI: https://doi.org/10.3803/EnM.2025.2846 [Epub ahead of print]

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Abstract PDF PubReader ePub: Atypical parathyroid tumors (APTs) are an uncommon subset of parathyroid neoplasms that carry substantial clinical relevance because of their histological and clinical resemblance to parathyroid cancer. Despite this importance, the diagnosis of APTs remains persistently challenging, even for experienced pathologists. Their histopathological features overlap extensively with those of parathyroid cancer, and at present, no specific immunohistochemical markers are available that can reliably distinguish between these entities. Moreover, the clinical manifestations of APTs are indistinguishable from those of parathyroid adenomas or true parathyroid cancer. A major concern is the uncertain malignant potential of APTs, which contributes to difficulties in prognostic prediction and the absence of standardized surveillance guidelines. Although most published studies suggest a benign clinical course for the majority of APTs, these conclusions are frequently limited by relatively short follow-up durations. This limitation is underscored by several case reports describing recurrence or metastatic disease in patients initially diagnosed with APTs, subsequently prompting reclassification as parathyroid cancer. Recent advances in molecular technologies, particularly RNA sequencing and genomic profiling, have facilitated novel approaches to risk assessment and prognostic evaluation in APTs. This review aims to provide a comprehensive overview of the diagnosis, clinical manifestations, and current molecular strategies used to assess the malignant potential of APTs.

Original Articles

Mineral, Bone & Muscle
Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study: Kyoung Min Kim, Seol A Jang, Nam Ki Hong, Chul Sik Kim, Yumie Rhee, Seok Won Park, Steven R. Cummings, Gi Hyeon Seo; Endocrinol Metab. 2024;39(6):946-955. Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2047

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

Citations

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Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint report by SIPMO AND SIOMMMS
Francesco Bertoldo, Cristina Eller-Vainicher, Vittorio Fusco, Rodolfo Mauceri, Jessica Pepe, Alberto Bedogni, Andrea Palermo, Umberto Romeo, Giuseppe Guglielmi, Giuseppina Campisi
Journal of Bone Oncology.2025; 50: 100656. CrossRef
Personalizing denosumab therapy in postmenopausal Indian women with osteoporosis: predictive role of bone turnover markers and body mass index in determining dosing interval
Vivek Jha, Sanjay K. Bhadada, Rimesh Pal, Chirag Kharbanda, Sudhaker D. Rao
Osteoporosis International.2025; 36(12): 2531. CrossRef

Mineral, Bone & Muscle
Differential Impact of Subcutaneous and Visceral Fat on Bone Changes after Gastrectomy: Sungjoon Cho, Sungjae Shin, Seunghyun Lee, Yumie Rhee, Hyoung-Il Kim, Namki Hong; Endocrinol Metab. 2024;39(4):632-640. Published online July 17, 2024; DOI: https://doi.org/10.3803/EnM.2024.1956

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Background
Osteoporosis and fragility fractures are crucial musculoskeletal complications in long-term survivors of gastric cancer. However, the relationship between changes in body composition after gastrectomy and bone loss has not been investigated. Therefore, this study aimed to explore whether computed tomography (CT)-derived body composition parameters are associated with bone loss after gastrectomy in patients with gastric cancer.
Methods
We retrospectively reviewed medical records and abdomen CT scans of patients who underwent gastrectomy at Yonsei University Severance Hospital between 2009 and 2018. Patients with non-metastatic gastric adenocarcinoma and preoperative and postoperative non-contrast CT scans were analyzed. Section area of skeletal muscle (SMA), visceral fat (VFA), and subcutaneous fat (SFA) were assessed using semi-automatic segmentation software. Changes in trabecular bone attenuation of L1 mid-vertebra level (L1 Hounsfield units [HU]) were measured.
Results
Fifty-seven patients (mean age, 65.5±10.6; 70.2% males) were analyzed, and the median duration was 31 months. Fortyseven patients (82.5%) lost weight after gastrectomy. Baseline SMA and VFA did not differ between the bone loss and preserved groups; however, baseline SFA was significantly higher in the bone preserved group than in the bone loss group (P=0.020). In a multivariable linear regression model adjusted for confounding factors, one standard deviation higher VFA at baseline was associated with greater annualized L1 HU loss (%) (P=0.034). However, higher preoperative SFA was associated with protection against bone loss after gastrectomy (P=0.025).
Conclusion
Higher preoperative SFA exhibited a protective effect against bone loss after gastrectomy in patients with non-metastatic gastric cancer, whereas VFA exhibited a negative effect.

Citations

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Body fat percentage and the outcomes of hip fractures in adults aged 50 years and above: a 1-year follow-up study
Wenliang Fan, Zhibang Zhao, Liqiang Wang, Qingbo Chu
Frontiers in Medicine.2025;[Epub] CrossRef
Calorie Restriction and Bone Health: Lessons from Bariatric Metabolic Surgery
Bukyung Kim
Endocrinology and Metabolism.2025; 40(3): 388. CrossRef
Differential associations of subcutaneous and visceral fat with bone turnover markers: A study on bariatric surgery patients with severe obesity and individuals without obesity
Prince Dadson, Eleni Rebelos, Maria K. Jaakkola, Milena Monfort-Pires, Ronja Ojala, Henri Honka, Kari K. Kalliokoski, Riku Klén, Pirjo Nuutila, Kaisa K. Ivaska
International Journal of Obesity.2025; 49(12): 2494. CrossRef

Mineral, Bone & Muscle
Age-Dependent Association of Height Loss with Incident Fracture Risk in Postmenopausal Korean Women: Chaewon Lee, Hye-Sun Park, Yumie Rhee, Namki Hong; Endocrinol Metab. 2023;38(6):669-678. Published online September 1, 2023; DOI: https://doi.org/10.3803/EnM.2023.1734

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Background
Height loss is a simple clinical measure associated with increased fracture risk. However, limited data exists on the association between height loss and fracture risk in postmenopausal Korean women. It is unknown whether this association varies with age.
Methods
Data on height loss over a 6-year period were collected from a community-based longitudinal follow-up cohort (Ansung cohort of the Korean Genome and Epidemiology Study). Incident fractures were defined based on self-reported fractures after excluding those due to severe trauma or toes/fingers. The association between incident fractures and height loss was investigated using a Cox proportional hazards model.
Results
During a median follow-up of 10 years after the second visit, 259/1,806 participants (median age, 64 years) experienced incident fractures. Overall, a 1 standard deviation (SD) decrease in height (1.6 cm/median 5.8 years) was associated with 9% increased risk of fracture (hazard ratio [HR], 1.09; P=0.037), which lost statistical significance after adjustment for covariates. When stratified into age groups (50–59, 60–69, 70 years or older), a 1 SD decrease in height remained a robust predictor of fracture in the 50 to 59 years age group after adjusting for covariates (adjusted hazard ratio [aHR], 1.52; P=0.003), whereas height loss was not an independent predictor of fracture in the 60 to 69 (aHR, 1.06; P=0.333) or the 70 years or older age groups (aHR, 1.05; P=0.700; P for interaction <0.05, for all).
Conclusion
Height loss during the previous 6 years was associated with an increased 10-year fracture risk in postmenopausal women in their 50s.

Citations

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Evolving trends of hand injuries in Korea (2010-2023): a comprehensive analysis and implications for hand surgeons
Daihun Kang
Archives of Hand and Microsurgery.2025; 30(1): 15. CrossRef
Spine age estimation using deep learning in lateral spine radiographs and DXA VFA to predict incident fracture and mortality
Sang Wouk Cho, Namki Hong, Kyoung Min Kim, Young Han Lee, Chang Oh Kim, Hyeon Chang Kim, Yumie Rhee, Brian H. Chen, William D. Leslie, Steven R. Cummings
npj Aging.2025;[Epub] CrossRef
A Bone Health Optimization Framework for Malaysia: a position paper by the Malaysian Bone Health Optimization Network (MyBONe)
Joon-Kiong Lee, Juzaily Fekry Leong, Fu-Yuen Thong, Mohd Ariff Sharifudin, Azlina Amir Abbas, Nur Azree Ferdaus Kamudin, Sanjiv Rampal, Nor Faissal Yasin, Kwong-Weng Loh, Chee-Ken Chan, Paul James Mitchell
Archives of Osteoporosis.2024;[Epub] CrossRef

Review Article

Mineral, Bone & Muscle
Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism: Hye-Sun Park, Namki Hong, Jong Ju Jeong, Mijin Yun, Yumie Rhee; Endocrinol Metab. 2022;37(5):744-755. Published online October 25, 2022; DOI: https://doi.org/10.3803/EnM.2022.1589

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Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi–single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient’s clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.

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Ruiying Zhu, Ning Yue, Yurong Hong, Qin Ye, Zhenyi Han, Zhiyan Luo, Chaoran Xie, Haichao Yan, Xing Yu
International Journal of Surgery.2026;[Epub] CrossRef
Algorithmic Surgical Management of Primary Hyperparathyroidism and Its Variants: A Scoping Review
Fleur Kabala, Todd Falcone, Kourosh Parham
The Laryngoscope.2026;[Epub] CrossRef
Diagnostic Ability and Correlation of Digital 11C-Methionine PET/CT in Primary Hyperparathyroidism with Inconclusive Standard Imaging
Hee Beom Jeong, Yong-il Kim, Soyoon Yoon, Dong Yun Lee, Beom-Jun Kim, Seung Hun Lee, Jin-Sook Ryu
Nuclear Medicine and Molecular Imaging.2025; 59(1): 72. CrossRef
Frequency and characteristics of ectopic parathyroid adenomas in a cohort of patients referred for 18F-fluorocholine PET/CT
Friso M. van der Zant, Maurits Wondergem, Wouter A.M. Broos, Sergiy V. Lazarenko, Remco J.J. Knol
Nuclear Medicine Communications.2025; 46(1): 89. CrossRef
Navigating diagnostic dilemmas: Localizing parathyroid adenoma in the presence of MIBI-avid thyroid nodules: A case report and literature review
Zohreh Maghsoomi, Maryam Rafieemanesh, Atefeh kashanizadeh, Behnaz Boozari, Mohammad Reza Babaei, Neda Hatami, Mohammad E․ Khamseh, Mehran Arab-Ahmadi
Radiology Case Reports.2025; 20(2): 1041. CrossRef
Localization in primary hyperparathyroidism
Piyush Aggarwal, Vinisha Gunasekaran, Ashwani Sood, Bhagwant Rai Mittal
Best Practice & Research Clinical Endocrinology & Metabolism.2025; 39(2): 101967. CrossRef
Correlation between parathyroid adenoma volume and perioperative outcomes in primary hyperparathyroidism: Does the size matter?
Antonio Fiore, Sophie Eschlböck, Céline Carlen, Ioannis I. Lazaridis, Alexandros Lalos, Raoul Droeser, Tarik Delko, Alberto Posabella
Updates in Surgery.2025; 77(2): 381. CrossRef
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Letizia Meomartino, Mattia Rossi, Gloria Selvatico, Ruth Rossetto Giaccherino, Loredana Pagano
Frontiers in Endocrinology.2025;[Epub] CrossRef
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Banyeswar Pal
International Journal of Research in Medical Sciences.2025; 13(3): 1238. CrossRef
Getting the timing right: An implementation study and pre post audit to implement evidence-based parathyroid scan guidelines
Amanda Tunstall, Katherine Harding, Amy M Dennett, Annie K Lewis
Journal of Medical Imaging and Radiation Sciences.2025; 56(4): 101894. CrossRef
Primary hyperparathyroidism during pregnancy: ultrasound as an accurate preoperative localization imaging modality
Mengyuan Zhou, Yudi He, Yanwen Luo, Ou Wang, Quan Liao, Yuxin Jiang, He Liu, Qingli Zhu
Orphanet Journal of Rare Diseases.2025;[Epub] CrossRef
US of the Neck beyond the Thyroid Gland: Parathyroid Glands
Rachita Khot, Irene Dixe de Oliveira Santo, Luyao Shen, Malak Itani, Anne Sailer, Jonathan D. Kirsch, Margarita V. Revzin
RadioGraphics.2025;[Epub] CrossRef
Primary Hyperparathyroidism: 18F-Fluorocholine PET/CT vs. 4D-CT for Parathyroid Identification: Toward a Comprehensive Diagnostic Framework—An Updated Review and Recommendations
Gregorio Scerrino, Nunzia Cinzia Paladino, Giuseppa Graceffa, Giuseppina Melfa, Giuseppina Orlando, Renato Di Vuolo, Chiara Lo Cicero, Alessandra Murabito, Stefano Radellini, Pierina Richiusa, Antonio Lo Casto
Journal of Clinical Medicine.2025; 14(15): 5468. CrossRef
Mediastinal parathyroid cyst: a diagnostic challenge
Andreia Martins Fernandes, Maria Inês Viegas, Carlos E Costa Almeida, Joana Couto
BMJ Case Reports.2025; 18(7): e266394. CrossRef
Diagnostic Accuracy of 4D CT in Detecting Parathyroid Adenoma Compared With Ultrasound and Sestamibi SPECT/CT in Primary Hyperparathyroidism: A Retrospective Study
Somdatta Giri, Krishnan Nagarajan, Balamourougan Krishnaraj, Debasis Gochhait, Madhusudhanan Ponnusamy, Anitha Sebastian, Baskararaj Sriviruthi, Jayaprakash Sahoo, Sadishkumar Kamalanathan, Dukhabandhu Naik
Cureus.2025;[Epub] CrossRef
Parathyroid disease diagnosis: A look at scintigraphy, ultrasound, and lab tests
Saeed M. Bafaraj
Current Problems in Diagnostic Radiology.2025;[Epub] CrossRef
Temporal Variation of Biochemical Markers and Adenoma Predictors in Normocalcemic Primary Hyperparathyroidism: A Multicenter Retrospective Analysis
Berçem Ayçiçek, Mazhar Müslüm Tuna, Ismail Engin, Mustafa Şahin, Sayid Zuhur, Neşe Ersöz Gülçelik, Hüseyin Yağcı, Ersen Karakılıç, Evin Bozkur, Bekir Çakır, Elif Güneş, Süleyman Baldane, Özen Öz Gül, Gulhan Akbaba, Cevdet Duran, Faruk Kılınç, Güven Barış
Clinical Endocrinology.2025; 103(6): 805. CrossRef
Expression of the Calcium-Sensing Receptor on Normal and Abnormal Parathyroid and Thyroid Tissue
Anne L. Worth, Mesrop Ayrapetyan, Susan J. Maygarden, Zibo Li, Zhanhong Wu, Chris B. Agala, Lawrence T. Kim
Journal of Surgical Research.2024; 293: 618. CrossRef
Use of [18F]fluorocholine PET/CT in the detection of primary hyperparathyroidism in paediatrics: a case report
Helena Martínez Sánchez, Francisca Moreno Macián, Sara León Cariñena, Carmen de Mingo Alemany, Lidia Blasco González, Raquel Sánchez Vañó
Journal of Pediatric Endocrinology and Metabolism.2024; 37(6): 580. CrossRef
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Pedro Polastri Lima Peixoto, Daniella de Freitas Pereira Calheir Durço, Luiz Carlos Conti de Freitas
BMJ Case Reports.2024; 17(7): e258728. CrossRef
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Kang Ning, Yongchao Yu, Xinyi Zheng, Zhenyu Luo, Zan Jiao, Xinyu Liu, Yiyao Wang, Yarong Liang, Zhuoqi Zhang, Xianglin Ye, Weirui Wu, Jian Bu, Qiaorong Chen, Fuxiang Cheng, Lizhen Liu, Mingjie Jiang, Ankui Yang, Tong Wu, Zhongyuan Yang
International Journal of Surgery.2024; 110(8): 5047. CrossRef
Bone Mineral Density and First Line Imaging with [18F]fluorocholine PET/CT in Normocalcemic and Hypercalcemic Primary Hyperparathyroidism: Results from a Single Center
Dagmar Schaffler-Schaden, Gregor Schweighofer-Zwink, Lukas Hehenwarter, Antje van der Zee-Neuen, Maria Flamm, Mohsen Beheshti, Christian Pirich
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Sunil Chumber, Gopal Puri, Reva S Sahu, Piyush Ranjan, Brijesh K Singh, Nishikant Damle
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Journal of Bone Metabolism.2023; 30(2): 201. CrossRef
Role of 18F-Fluorocholine Positron Emission Tomography (PET)/Computed Tomography (CT) in Diagnosis of Elusive Parathyroid Adenoma
Janan R Badier, Pokhraj P Suthar, Jagadeesh S Singh, Miral D Jhaveri
Cureus.2023;[Epub] CrossRef
Pitfalls of DualTracer 99m-Technetium (Tc) Pertechnetate and Sestamibi Scintigraphy before Parathyroidectomy: Between Primary-Hyperparathyroidism-Associated Parathyroid Tumour and Ectopic Thyroid Tissue
Mara Carsote, Mihaela Stanciu, Florina Ligia Popa, Oana-Claudia Sima, Eugenia Petrova, Anca-Pati Cucu, Claudiu Nistor
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Original Articles

Diabetes, Obesity and Metabolism
Association of Shift Work with Normal-Weight Obesity in Community-Dwelling Adults: Chul Woo Ahn, Sungjae Shin, Seunghyun Lee, Hye-Sun Park, Namki Hong, Yumie Rhee; Endocrinol Metab. 2022;37(5):781-790. Published online October 25, 2022; DOI: https://doi.org/10.3803/EnM.2022.1532

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Background
Shift work is associated with obesity and metabolic syndrome. However, this association in the normal-weight population remains unclear. This study aimed to investigate whether shift work is associated with normal-weight obesity (NWO).
Methods
From the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) dataset (2008 to 2011), 3,800 full-time workers aged ≥19 years with a body mass index (BMI) ≤25 kg/m² were analysed. We defined NWO as BMI ≤25 kg/m² and body fat percentage ≥25% in men and ≥37% in women. Working patterns were classified into “daytime,” “other than daytime,” and “shift.” Multivariable logistic regression analysis was performed to evaluate the relationship between shift work and NWO.
Results
Shift work was associated with higher odds of NWO than daytime work (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.04 to 2.09) and night/evening work (aOR, 1.87; 95% CI, 1.11 to 3.14) after adjustment for type of work, working hours, age, sex, BMI, 25-hydroxyvitamin D levels, homeostatic model assessment for insulin resistance, and other sociodemographic factors. In subgroup analyses, the association between shift work and NWO was more robust in those aged ≥60 years and those working ≥56 hours/week.
Conclusion
Shift work was associated with NWO in community-dwelling Korean adults, independent of age, sex, BMI, and other covariates.

Citations

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The research progress and prospects of circadian rhythm in obesity: a bibliometric analysis
Ye Dou, Xiaojin Guo, Xuefei Wang, Aolong He, Fanghe Li, Kuo Gao
Frontiers in Nutrition.2025;[Epub] CrossRef
Normal Weight Obesity Overview and Update: A narrative review
Antonino De Lorenzo, Paola Gualtieri, Giulia Frank, Roselisa Palma, Rossella Cianci, Leonardo Romano, Lucilla Ciancarella, Glauco Raffaelli, Laura Di Renzo
Current Obesity Reports.2025;[Epub] CrossRef
Development and interpretation of a machine learning predictive model for early cognitive impairment in hypertension associated with environmental factors
Xia Zhong, Tianen Zhao, Shimeng Lv, Guangheng Zhang, Jing Li, Donghai Liu, Huachen Jiao
Frontiers in Cardiovascular Medicine.2025;[Epub] CrossRef
Association of Shift Work, Sociodemographic Variables and Healthy Habits with Obesity Scales
Javier Tosoratto, Pedro Juan Tárraga López, Ángel Arturo López-González, Daniela Vallejos, Emilio Martínez-Almoyna Rifá, José Ignacio Ramirez-Manent
Life.2024; 14(11): 1503. CrossRef
Impaired Melatonin Secretion, Oxidative Stress and Metabolic Syndrome in Night Shift Work
Sorina Hohor, Cristina Mandanach, Andreea Maftei, Corina Aurelia Zugravu, Marina Ruxandra Oțelea
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Normal-Weight Obesity and Metabolic Syndrome in Korean Adults: A Population-Based Cross-Sectional Study
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Mineral, Bone & Muscle
Real-World Safety and Effectiveness of Denosumab in Patients with Osteoporosis: A Prospective, Observational Study in South Korea: Yumie Rhee, Dong-Gune Chang, Jeonghoon Ha, Sooa Kim, Yusun Lee, Euna Jo, Jung-Min Koh; Endocrinol Metab. 2022;37(3):497-505. Published online June 3, 2022; DOI: https://doi.org/10.3803/EnM.2022.1427

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Background
The efficacy and safety of denosumab have been established in a phase 3, randomized, placebo-controlled trial in Korean postmenopausal women with osteoporosis. This postmarketing surveillance study was aimed to investigate the safety and effectiveness of denosumab in Korean real-world clinical practice.
Methods
Patients with osteoporosis who had received denosumab per the Korean approved indications in the postmarketing setting between September 2014 and September 2019 were enrolled. The primary endpoint was the incidence of adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was the percent change from baseline in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck.
Results
Of the 3,221 patients enrolled, 3,185 were included in the safety analysis set; 2,973 (93.3%) were female, and the mean± standard deviation (SD) age was 68.9±9.9 years. The mean±SD study period was 350.0±71.4 days. AEs, fatal AEs, and ADRs occurred in 19.3%, 0.8%, and 1.6%, respectively. The most frequent AEs, occurring in >0.5% of patients, were dizziness (0.7%), arthralgia (0.7%), back pain (0.6%), and myalgia (0.6%). Hypocalcemia occurred in 0.3% of patients. There were no cases of osteonecrosis of the jaw and atypical femoral fracture. Mean±SD percent change from baseline in BMD of the lumbar spine, total hip, and femoral neck was 7.3%±23.6%, 3.6%±31.4%, and 3.2%±10.7%, respectively.
Conclusion
The safety and effectiveness of denosumab in Korean patients with osteoporosis in this study were comparable with those in the Korean randomized controlled trial, with no new safety findings.

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Junghye Hwang, Youngjae Yoon, Garam Byun, Byung‐Joon Choi, Joo‐Young Ohe, Baek‐Soo Lee, Junho Jung
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Ali Afshari, Jafar Karami, Mitra Abbasifard
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Jeonghoon Ha, Kyong Yeun Jung, Kyoung Jin Kim, Seong Hee Ahn, Hyo-Jeong Kim, Yoon-Sok Chung
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Yehao Lin, Yidong Xu, Siyue Zhou, Junyu Liu, Min Zhang, Baoxin Zhang, Haixia Chen
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Mineral, Bone & Muscle
Computed Tomography-Derived Skeletal Muscle Radiodensity Is an Early, Sensitive Marker of Age-Related Musculoskeletal Changes in Healthy Adults: Yeon Woo Jung, Namki Hong, Joon Chae Na, Woong Kyu Han, Yumie Rhee; Endocrinol Metab. 2021;36(6):1201-1210. Published online December 13, 2021; DOI: https://doi.org/10.3803/EnM.2021.1206

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Background
A decrease in computed tomography (CT)-derived skeletal muscle radiodensity (SMD) reflects age-related ectopic fat infiltration of muscle, compromising muscle function and metabolism. We investigated the age-related trajectory of SMD and its association with vertebral trabecular bone density in healthy adults.
Methods
In a cohort of healthy adult kidney donors aged 19 to 69 years (n=583), skeletal muscle index (SMI, skeletal muscle area/height2), SMD, and visceral-to-subcutaneous fat (V/S) ratio were analyzed at the level of L3 from preoperative CT scans. Low bone mass was defined as an L1 trabecular Hounsfield unit (HU) <160 HU.
Results
L3SMD showed constant decline from the second decade (annual change –0.38% and –0.43% in men and women), whereas the decline of L3SMI became evident only after the fourth decade of life (–0.37% and –0.18% in men and women). One HU decline in L3SMD was associated with elevated odds of low bone mass (adjusted odds ratio, 1.07; 95% confidence interval, 1.02 to 1.13; P=0.003), independent of L3SMI, age, sex, and V/S ratio, with better discriminatory ability compared to L3SMI (area under the receiver-operating characteristics curve 0.68 vs. 0.53, P<0.001). L3SMD improved the identification of low bone mass when added to age, sex, V/S ratio, and L3SMI (category-free net reclassification improvement 0.349, P<0.001; integrated discrimination improvement 0.015, P=0.0165).
Conclusion
L3SMD can be an early marker for age-related musculoskeletal changes showing linear decline throughout life from the second decade in healthy adults, with potential diagnostic value for individuals with low bone mass.

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Adrenal Gland
Metabolic Subtyping of Adrenal Tumors: Prospective Multi-Center Cohort Study in Korea: Eu Jeong Ku, Chaelin Lee, Jaeyoon Shim, Sihoon Lee, Kyoung-Ah Kim, Sang Wan Kim, Yumie Rhee, Hyo-Jeong Kim, Jung Soo Lim, Choon Hee Chung, Sung Wan Chun, Soon-Jib Yoo, Ohk-Hyun Ryu, Ho Chan Cho, A Ram Hong, Chang Ho Ahn, Jung Hee Kim, Man Ho Choi; Endocrinol Metab. 2021;36(5):1131-1141. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1149

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Background
Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids.
Methods
The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors.
Results
The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT.
Conclusion
The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

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Special Article

Adrenal gland
Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force: Eu Jeong Ku, Kyoung Jin Kim, Jung Hee Kim, Mi Kyung Kim, Chang Ho Ahn, Kyung Ae Lee, Seung Hun Lee, You-Bin Lee, Kyeong Hye Park, Yun Mi Choi, Namki Hong, A Ram Hong, Sang-Wook Kang, Byung Kwan Park, Moon-Woo Seong, Myungshin Kim, Kyeong Cheon Jung, Chan Kwon Jung, Young Seok Cho, Jin Chul Paeng, Jae Hyeon Kim, Ohk-Hyun Ryu, Yumie Rhee, Chong Hwa Kim, Eun Jig Lee; Endocrinol Metab. 2021;36(2):322-338. Published online April 6, 2021; DOI: https://doi.org/10.3803/EnM.2020.908

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Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.

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Original Article

Clinical Study
Genetic Analysis and Clinical Characteristics of Hereditary Pheochromocytoma and Paraganglioma Syndrome in Korean Population: Heewon Choi, Kyoung Jin Kim, Namki Hong, Saeam Shin, Jong-Rak Choi, Sang Wook Kang, Seung Tae Lee, Yumie Rhee; Endocrinol Metab. 2020;35(4):858-872. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.683

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Background
Pheochromocytoma and paragangliomas (PPGL) are hereditary in approximately 30% to 40% cases. With the advancement of genetic analysis techniques, including next-generation sequencing (NGS), there were attempts to classify PPGL into molecular clusters. With NGS being applied to clinical settings recently, we aimed to review the results of genetic analysis, including NGS, and investigate the association with clinical characteristics in Korean PPGL patients.
Methods
We reviewed the medical records of PPGL patients who visited Severance hospital from 2006 to 2019. We documented the clinical phenotype of those who underwent targeted NGS or had known germline mutations of related genes.
Results
Among 57 PPGL patients, we found 28 pathogenic germline mutations of susceptibility genes. Before the targeted NGS was implemented, only obvious syndromic feature lead to the Sanger sequencing for the specific genes. Therefore, for the exact prevalence, only patients after the year 2017, when targeted NGS was added, were included (n=43). The positive germline mutations were found in 14 patients; thus, the incidence rate is 32.6%. Patients with germline mutations had a higher likelihood of family history. There were significant differences in the type of PPGLs, percentage of family history, metastasis rate, presence of other tumors, and biochemical profile among three molecular clusters: pseudohypoxic tricarboxylic acid cycle-related, pseudohypoxic von Hippel-Lindau (VHL)/endothelial PAS domain-containing protein 1-related, and kinase-signaling group. Germline mutations were identified in seven PPGL-related genes (SDHB, RET, VHL, NF1, MAX, SDHA, and SDHD).
Conclusion
We report the expected prevalence of germline mutations in Korean PPGL patients. NGS is a useful and accessible tool for genetic analysis in patients with PPGLs, and further research on molecular classification is needed for precise management.

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Corrigendum

Miscellaneous
Corrigendum: IRB Approval Number Correction. Cardiac Dysfunction in Association with Increased Inflammatory Markers in Primary Aldosteronism: Jung Soo Lim, Sungha Park, Sung Il Park, Young Taik Oh, Eun Hee Choi, Jang Young Kim, Yumie Rhee; Endocrinol Metab. 2020;35(3):671. Published online July 30, 2020; DOI: https://doi.org/10.3803/EnM.2020.305; Corrects: Endocrinol Metab 2016;31(4):567

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Review Article

Miscellaneous
Machine Learning Applications in Endocrinology and Metabolism Research: An Overview: Namki Hong, Heajeong Park, Yumie Rhee; Endocrinol Metab. 2020;35(1):71-84. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.71

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Machine learning (ML) applications have received extensive attention in endocrinology research during the last decade. This review summarizes the basic concepts of ML and certain research topics in endocrinology and metabolism where ML principles have been actively deployed. Relevant studies are discussed to provide an overview of the methodology, main findings, and limitations of ML, with the goal of stimulating insights into future research directions. Clear, testable study hypotheses stem from unmet clinical needs, and the management of data quality (beyond a focus on quantity alone), open collaboration between clinical experts and ML engineers, the development of interpretable high-performance ML models beyond the black-box nature of some algorithms, and a creative environment are the core prerequisites for the foreseeable changes expected to be brought about by ML and artificial intelligence in the field of endocrinology and metabolism, with actual improvements in clinical practice beyond hype. Of note, endocrinologists will continue to play a central role in these developments as domain experts who can properly generate, refine, analyze, and interpret data with a combination of clinical expertise and scientific rigor.

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Original Articles

Adrenal gland
Effects of Altered Calcium Metabolism on Cardiac Parameters in Primary Aldosteronism: Jung Soo Lim, Namki Hong, Sungha Park, Sung Il Park, Young Taik Oh, Min Heui Yu, Pil Yong Lim, Yumie Rhee; Endocrinol Metab. 2018;33(4):485-492. Published online November 30, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.4.485

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Background

Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA.

Methods

Forty-two patients (mean age 48.8±10.9 years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins.

Results

The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was 8.9±0.3 mg/dL (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ρ=−0.424, P=0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (β=−0.366, P=0.068 and β=−0.252, P=0.070, respectively).

Conclusion

Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.

Citations

Citations to this article as recorded by

Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis
Anning Wang, Yuhan Wang, Hongzhou Liu, Xiaodong Hu, Jiefei Li, Huaijin Xu, Zhimei Nie, Lingjing Zhang, Zhaohui Lyu
Frontiers in Endocrinology.2022;[Epub] CrossRef

Adrenal gland
C-Arm Computed Tomography-Assisted Adrenal Venous Sampling Improved Right Adrenal Vein Cannulation and Sampling Quality in Primary Aldosteronism: Chung Hyun Park, Namki Hong, Kichang Han, Sang-Wook Kang, Cho Rok Lee, Sungha Park, Yumie Rhee; Endocrinol Metab. 2018;33(2):236-244. Published online May 4, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.236

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Background

Adrenal venous sampling (AVS) is a gold standard for subtype classification of primary aldosteronism (PA). However, this procedure has a high failure rate because of the anatomical difficulties in accessing the right adrenal vein. We investigated whether C-arm computed tomography-assisted AVS (C-AVS) could improve the success rate of adrenal sampling.

Methods

A total of 156 patients, diagnosed with PA who underwent AVS from May 2004 through April 2017, were included. Based on the medical records, we retrospectively compared the overall, left, and right catheterization success rates of adrenal veins during the periods without C-AVS (2004 to 2010, n=32) and with C-AVS (2011 to 2016, n=124). The primary outcome was adequate bilateral sampling defined as a selectivity index (SI) >5.

Results

With C-AVS, the rates of adequate bilateral AVS increased from 40.6% to 88.7% (P<0.001), with substantial decreases in failure rates (43.7% to 0.8%, P<0.001). There were significant increases in adequate sampling rates from right (43.7% to 91.9%, P<0.001) and left adrenal veins (53.1% to 95.9%, P<0.001) as well as decreases in catheterization failure from right adrenal vein (9.3% to 0.0%, P<0.001). Net improvement of SI on right side remained significant after adjustment for left side (adjusted SI, 1.1 to 9.0; P=0.038). C-AVS was an independent predictor of adequate bilateral sampling in the multivariate model (odds ratio, 9.01; P<0.001).

Conclusion

C-AVS improved the overall success rate of AVS, possibly as a result of better catheterization of right adrenal vein.

Citations

Citations to this article as recorded by

Utility of right adrenal signature veins in venous sampling for primary aldosteronism
Zhenglin Shen, Shaoyong Xu, Siyu Guan, Bo Chen, Qingan Li, Ming Yu, Zhao Gao
Annals of Medicine.2023;[Epub] CrossRef
Key to the Treatment of Primary Aldosteronism in Secondary Hypertension: Subtype Diagnosis
Rui Zuo, Shuang Liu, Lu Xu, Hua Pang
Current Hypertension Reports.2023; 25(12): 471. CrossRef
A clinical assessment of portable point-of-care testing for quick cortisol assay during adrenal vein sampling
Ko Aiga, Mitsuhiro Kometani, Shigehiro Karashima, Seigo Konishi, Takuya Higashitani, Daisuke Aono, Xurong Mai, Mikiya Usukura, Takahiro Asano, Ayako Wakayama, Yuko Noda, Wataru Koda, Tetsuya Minami, Satoshi Kobayashi, Toshinori Murayama, Takashi Yoneda
Scientific Reports.2023;[Epub] CrossRef
Does Intraprocedural CT Improve the Success Rate of Adrenal Venous Sampling? A Systematic Review and Meta-Analysis of Data from 809 Patients
Nima Hafezi-Nejad, David M. Gullotti, Christopher R. Bailey, Mark L. Lessne, Brian P. Holly
CardioVascular and Interventional Radiology.2022; 45(1): 29. CrossRef
Prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea
Minjae Yoon, Namki Hong, Jaehyung Ha, Chan Joo Lee, Cheol Ryong Ku, Yumie Rhee, Sungha Park
Hypertension Research.2022; 45(9): 1418. CrossRef
Cone-beam computed tomography is not a mandatory procedure in adrenal venous sampling for primary hyperaldosteronism
Ran Cai, Chao Hu, Hai-Yang Li
BMC Medical Imaging.2022;[Epub] CrossRef
Adrenal Venous Sampling for Subtype Diagnosis of Primary Hyperaldosteronism
Mitsuhide Naruse, Akiyo Tanabe, Koichi Yamamoto, Hiromi Rakugi, Mitsuhiro Kometani, Takashi Yoneda, Hiroki Kobayashi, Masanori Abe, Youichi Ohno, Nobuya Inagaki, Shoichiro Izawa, Masakatsu Sone
Endocrinology and Metabolism.2021; 36(5): 965. CrossRef
Controversies and advances in adrenal venous sampling in the diagnostic workup of primary aldosteronism
Martin Wolley, Moe Thuzar, Michael Stowasser
Best Practice & Research Clinical Endocrinology & Metabolism.2020; 34(3): 101400. CrossRef
Update on the Aldosterone Resolution Score and Lateralization in Patients with Primary Aldosteronism
Eun-Hee Cho
Endocrinology and Metabolism.2018; 33(3): 352. CrossRef

Site-Specific Difference of Bone Geometry Indices in Hypoparathyroid Patients: Hye-Sun Park, Da Hea Seo, Yumie Rhee, Sung-Kil Lim; Endocrinol Metab. 2017;32(1):68-76. Published online February 6, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.1.68

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Background

Hypoparathyroid patients often have a higher bone mineral density (BMD) than the general population. However, an increase in BMD does not necessarily correlate with a solid bone microstructure. This study aimed to evaluate the bone microstructure of hypoparathyroid patients by using hip structure analysis (HSA).

Methods

Ninety-five hypoparathyroid patients >20 years old were enrolled and 31 of them had eligible data for analyzing bone geometry parameters using HSA. And among the control data, we extracted sex-, age-, and body mass index-matched three control subjects to each patient. The BMD data were reviewed retrospectively and the bone geometry parameters of the patients were analyzed by HSA.

Results

The mean Z-scores of hypoparathyroid patients at the lumbar spine, femoral neck, and total hip were above zero (0.63±1.17, 0.48±1.13, and 0.62±1.10, respectively). The differences in bone geometric parameters were site specific. At the femoral neck and intertrochanter, the cross-sectional area (CSA) and cortical thickness (C.th) were higher, whereas the buckling ratio (BR) was lower than in controls. However, those trends were opposite at the femoral shaft; that is, the CSA and C.th were low and the BR was high.

Conclusion

Our study shows the site-specific effects of hypoparathyroidism on the bone. Differences in bone components, marrow composition, or modeling based bone formation may explain these findings. However, further studies are warranted to investigate the mechanism, and its relation to fracture risk.

Citations

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Vertebral fractures, trabecular bone score and their determinants in chronic hypoparathyroidism
S. Saha, V. Mannar, D. Kandasamy, V. Sreenivas, R. Goswami
Journal of Endocrinological Investigation.2022; 45(9): 1777. CrossRef
Epidemiology and Financial Burden of Adult Chronic Hypoparathyroidism
Sigridur Bjornsdottir, Steven Ing, Deborah M Mitchell, Tanja Sikjaer, Line Underbjerg, Zaki Hassan-Smith, Jad Sfeir, Neil J Gittoes, Bart L Clarke L
Journal of Bone and Mineral Research.2020; 37(12): 2602. CrossRef
Effect of Endogenous Parathyroid Hormone on Bone Geometry and Skeletal Microarchitecture
A Ram Hong, Ji Hyun Lee, Jung Hee Kim, Sang Wan Kim, Chan Soo Shin
Calcified Tissue International.2019; 104(4): 382. CrossRef
Bone responses to chronic treatment of adult hypoparathyroid patients with PTH peptides
Sofie Malmstroem, Lars Rejnmark, Dolores M. Shoback
Current Opinion in Endocrine and Metabolic Research.2018; 3: 51. CrossRef

Clinical Study
Cardiac Dysfunction in Association with Increased Inflammatory Markers in Primary Aldosteronism: Jung Soo Lim, Sungha Park, Sung Il Park, Young Taik Oh, Eunhee Choi, Jang Young Kim, Yumie Rhee; Endocrinol Metab. 2016;31(4):567-576. Published online November 3, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.567; Correction in: Endocrinol Metab 2020;35(3):671

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Background

Oxidative stress in primary aldosteronism (PA) is thought to worsen aldosterone-induced damage by activating proinflammatory processes. Therefore, we investigated whether inflammatory markers associated with oxidative stress is increased with negative impacts on heart function as evaluated by echocardiography in patients with PA.

Methods

Thirty-two subjects (mean age, 50.3±11.0 years; 14 males, 18 females) whose aldosterone-renin ratio was more than 30 among patients who visited Severance Hospital since 2010 were enrolled. Interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein 1, tumor necrosis factor α (TNF-α), and matrix metalloproteinase 2 (MMP-2), and MMP-9 were measured. All patients underwent adrenal venous sampling with complete access to both adrenal veins.

Results

Only MMP-2 level was significantly higher in the aldosterone-producing adenoma (APA) group than in the bilateral adrenal hyperplasia (BAH). Patients with APA had significantly higher left ventricular (LV) mass and A velocity, compared to those with BAH. IL-1β was positively correlated with left atrial volume index. Both TNF-α and MMP-2 also had positive linear correlation with A velocity. Furthermore, MMP-9 showed a positive correlation with LV mass, whereas it was negatively correlated with LV end-systolic diameter.

Conclusion

These results suggest the possibility that some of inflammatory markers related to oxidative stress may be involved in developing diastolic dysfunction accompanied by LV hypertrophy in PA. Further investigations are needed to clarify the role of oxidative stress in the course of cardiac remodeling.

Citations

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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
The role of the mineralocorticoid receptor in immune cells in cardiovascular disease
Charlotte D. C. C. van der Heijden, Marlies Bode, Niels P. Riksen, Ulrich O. Wenzel
British Journal of Pharmacology.2022; 179(13): 3135. CrossRef
Prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea
Minjae Yoon, Namki Hong, Jaehyung Ha, Chan Joo Lee, Cheol Ryong Ku, Yumie Rhee, Sungha Park
Hypertension Research.2022; 45(9): 1418. CrossRef
Functional Characteristic and Significance of Aldosterone-Producing Cell Clusters in Primary Aldosteronism and Age-Related Hypertension
Fatin Athirah Pauzi, Elena Aisha Azizan
Frontiers in Endocrinology.2021;[Epub] CrossRef
Aldosterone-Regulating Receptors and Aldosterone-Driver Somatic Mutations
Jung Soo Lim, Samuel W. Plaska, Juilee Rege, William E. Rainey, Adina F. Turcu
Frontiers in Endocrinology.2021;[Epub] CrossRef
Time-Dependent Risk of Atrial Fibrillation in Patients With Primary Aldosteronism After Medical or Surgical Treatment Initiation
Kyoung Jin Kim, Namki Hong, Min Heui Yu, Hokyou Lee, Seunghyun Lee, Jung Soo Lim, Yumie Rhee
Hypertension.2021; 77(6): 1964. CrossRef
Serum Matrix Metalloproteinases and Left Atrial Remodeling—The Hoorn Study
Pauline B. C. Linssen, Hans-Peter Brunner-La Rocca, Casper G. Schalkwijk, Joline W. J. Beulens, Petra J. M. Elders, Amber A. van der Heijden, Roderick C. Slieker, Coen D. A. Stehouwer, Ronald M. A. Henry
International Journal of Molecular Sciences.2020; 21(14): 4944. CrossRef
Endothelial Dysfunction in Primary Aldosteronism
Zheng-Wei Chen, Cheng-Hsuan Tsai, Chien-Ting Pan, Chia-Hung Chou, Che-Wei Liao, Chi-Sheng Hung, Vin-Cent Wu, Yen-Hung Lin
International Journal of Molecular Sciences.2019; 20(20): 5214. CrossRef
IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis
Chia-Hung Chou, Chi-Sheng Hung, Che-Wei Liao, Lin-Hung Wei, Ching-Way Chen, Chia-Tung Shun, Wen-Fen Wen, Cho-Hua Wan, Xue-Ming Wu, Yi-Yao Chang, Vin-Cent Wu, Kwan-Dun Wu, Yen-Hung Lin
Cardiovascular Research.2018; 114(5): 690. CrossRef
European Heart Rhythm Association (EHRA) position paper on arrhythmia management and device therapies in endocrine disorders, endorsed by Asia Pacific Heart Rhythm Society (APHRS) and Latin American Heart Rhythm Society (LAHRS)
Bulent Gorenek, Giuseppe Boriani, Gheorge-Andrei Dan, Laurent Fauchier, Guilherme Fenelon, He Huang, Gulmira Kudaiberdieva, Gregory Y H Lip, Rajiv Mahajan, Tatjana Potpara, Juan David Ramirez, Marc A Vos, Francisco Marin, Carina Blomstrom-Lundqvist, Aldo
EP Europace.2018; 20(6): 895. CrossRef
Effects of Altered Calcium Metabolism on Cardiac Parameters in Primary Aldosteronism
Jung Soo Lim, Namki Hong, Sungha Park, Sung Il Park, Young Taik Oh, Min Heui Yu, Pil Yong Lim, Yumie Rhee
Endocrinology and Metabolism.2018; 33(4): 485. CrossRef
The mineralocorticoid receptor as a modulator of innate immunity and atherosclerosis
Charlotte D C C van der Heijden, Jaap Deinum, Leo A B Joosten, Mihai G Netea, Niels P Riksen
Cardiovascular Research.2018; 114(7): 944. CrossRef

Clinical Study
Serum γ-Glutamyl Transferase Is Inversely Associated with Bone Mineral Density Independently of Alcohol Consumption: Han Seok Choi, Kwang Joon Kim, Yumie Rhee, Sung-Kil Lim; Endocrinol Metab. 2016;31(1):64-71. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.64

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Background

γ-Glutamyl transferase (GGT) is a well-known marker of chronic alcohol consumption or hepatobiliary diseases. A number of studies have demonstrated that serum levels of GGT are independently associated with cardiovascular and metabolic disorders. The purpose of this study was to test if serum GGT levels are associated with bone mineral density (BMD) in Korean adults.

Methods

A total of 462 subjects (289 men and 173 women), who visited Severance Hospital for medical checkup, were included in this study. BMD was measured using dual energy X-ray absorptiometry. Cross-sectional association between serum GGT and BMD was evaluated.

Results

As serum GGT levels increased from the lowest tertile (tertile 1) to the highest tertile (tertile 3), BMD decreased after adjusting for confounders such as age, body mass index, amount of alcohol consumed, smoking, regular exercise, postmenopausal state (in women), hypertension, diabetes mellitus, and hypercholesterolemia. A multiple linear regression analysis showed a negative association between log-transformed serum GGT levels and BMD. In a multiple logistic regression analysis, tertile 3 of serum GGT level was associated with an increased risk for low bone mass compared to tertile 1 (odds ratio, 2.271; 95% confidence interval, 1.340 to 3.850; P=0.002).

Conclusion

Serum GGT level was inversely associated with BMD in Korean adults. Further study is necessary to fully elucidate the mechanism of the inverse relationship.

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Won-Young Lee
Endocrinology and Metabolism.2017; 32(1): 62. CrossRef

Case Report

Adrenal gland
Untreated Congenital Adrenal Hyperplasia with 17-α Hydroxylase/17,20-Lyase Deficiency Presenting as Massive Adrenocortical Tumor: Su Jin Lee, Je Eun Song, Sena Hwang, Ji-Yeon Lee, Hye-Sun Park, Seunghee Han, Yumie Rhee; Endocrinol Metab. 2015;30(3):408-413. Published online August 4, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.408

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Congenital adrenal hyperplasia (CAH) with 17α-hydroxylase/17,20-lyase deficiency is usually characterized by hypertension and primary amenorrhea, sexual infantilism in women, and pseudohermaphroditism in men. hypertension, and sexual infantilism in women and pseudohermaphroditism in men. In rare cases, a huge adrenal gland tumor can present as a clinical manifestation in untreated CAH. Adrenal cortical adenoma is an even more rare phenotype in CAH with 17α-hydroxylase/17,20-lyase deficiency. A 36-year-old female presented with hypertension and abdominal pain caused by a huge adrenal mass. Due to mass size and symptoms, left adrenalectomy was performed. After adrenalectomy, blood pressure remained high. Based on hormonal and genetic evaluation, the patient was diagnosed as CAH with 17α-hydroxylase/17,20-lyase deficiency. The possibility of a tumorous change in the adrenal gland due to untreated CAH should be considered. It is important that untreated CAH not be misdiagnosed as primary adrenal tumor as these conditions require different treatments. Adequate suppression of adrenocorticotropic hormone (ACTH) in CAH is also important to treat and to prevent the tumorous changes in the adrenal gland. Herein, we report a case of untreated CAH with 17α-hydroxylase/17,20-lyase deficiency presenting with large adrenal cortical adenoma and discuss the progression of adrenal gland hyperplasia due to inappropriate suppression of ACTH secretion.

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Jian Li, Yangguang Lu
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Uncommon adrenal rest tumors and massive adrenal enlargement in adult with congenital adrenal hyperplasia mimicking metastasis from pleomorphic sarcoma
Pierluigi Mazzeo, Irene Tizianel, Francesca Galuppini, Marta Sbaraglia, Mattia Barbot
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Rare Types of Congenital Adrenal Hyperplasias Other Than 21-hydroxylase Deficiency
Mehmet İsakoca, Şenay Erdeve, Semra Çetinkaya
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Congenital adrenal hyperplasia disorder due to 17 α-hydroxylase deficiency: a case report
Yunling Tian, Lijie Hou, Shulan Xiang, Xuguang Tian, Jinhui Xu
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Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia
Mara Carsote, Ana-Maria Gheorghe, Claudiu Nistor, Alexandra-Ioana Trandafir, Oana-Claudia Sima, Anca-Pati Cucu, Adrian Ciuche, Eugenia Petrova, Adina Ghemigian
Biomedicines.2023; 11(11): 3081. CrossRef
17α-Hydroxylase/17,20-Lyase Deficiency in 46,XY: Our Experience and Review of Literature
Madhur Maheshwari, Sneha Arya, Anurag Ranjan Lila, Vijaya Sarathi, Rohit Barnabas, Khushnandan Rai, Vishwambhar Vishnu Bhandare, Saba Samad Memon, Manjiri Pramod Karlekar, Virendra Patil, Nalini S Shah, Ambarish Kunwar, Tushar Bandgar
Journal of the Endocrine Society.2022;[Epub] CrossRef
17α-hydroxylase Deficiency Mimicking Hyperaldosteronism by Aldosterone-producing Adrenal Adenoma
Yun Kyung Cho, Hyeseon Oh, Sun-myoung Kang, Sujong An, Jin-Young Huh, Ji-Hyang Lee, Woo Je Lee
The Korean Journal of Medicine.2016; 91(2): 191. CrossRef

Original Articles

Mineral, Bone & Muscle
Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors: Wonjin Kim, Yoonjung Chung, Se Hwa Kim, Sehee Park, Jae Hyun Bae, Gyuri Kim, Su Jin Lee, Jo Eun Kim, Byeong-Woo Park, Sung-Kil Lim, Yumie Rhee; Endocrinol Metab. 2015;30(1):58-64. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.58

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Background

Sclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs), which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass. We analyzed changes in serum sclerostin levels in Korean women with breast cancer who were treated with an AI.

Methods

We included postmenopausal women with endocrine-responsive breast cancer (n=90; mean age, 57.7 years) treated with an AI, and compared them to healthy premenopausal women (n=36; mean age, 28.0 years). The subjects were randomly assigned to take either 5 mg alendronate with 0.5 µg calcitriol (n=46), or placebo (n=44) for 6 months.

Results

Postmenopausal women with breast cancer had significantly higher sclerostin levels compared to those in premenopausal women (27.8±13.6 pmol/L vs. 23.1±4.8 pmol/L, P<0.05). Baseline sclerostin levels positively correlated with either lumbar spine or total hip bone mineral density only in postmenopausal women (r=0.218 and r=0.233; P<0.05, respectively). Serum sclerostin levels increased by 39.9%±10.2% 6 months after AI use in postmenopausal women; however, no difference was observed between the alendronate and placebo groups (39.9%±10.2% vs. 55.9%±9.13%, P>0.05).

Conclusion

Serum sclerostin levels increased with absolute deficiency of residual estrogens in postmenopausal women with endocrine-responsive breast cancer who underwent AI therapy with concurrent bone loss.

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Role of SOST in Response to Mechanical Stimulation in Bone and Extraosseous Organs
Minyou Chen, Wenjing Li, Le Lei, Lingli Zhang
Biomolecules.2025; 15(6): 856. CrossRef
Voluntary Wheel Running Partially Compensates for the Effects of Global Estrogen Receptor-α Knockout on Cortical Bone in Young Male Mice
Rebecca K. Dirkes, Nathan C. Winn, Thomas J. Jurrissen, Dennis B. Lubahn, Victoria J. Vieira-Potter, Jaume Padilla, Pamela S. Hinton
International Journal of Molecular Sciences.2021; 22(4): 1734. CrossRef
Role of Osteocytes in Cancer Progression in the Bone and the Associated Skeletal Disease
Manish Adhikari, Jesús Delgado-Calle
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Gestational and lactational exposure to BPA or BPS has minimal effects on skeletal outcomes in adult female mice
Rebecca K. Dirkes, Rebecca J. Welly, Jiude Mao, Jessica Kinkade, Victoria J. Vieira-Potter, Cheryl S. Rosenfeld, Pamela S. Bruzina
Bone Reports.2021; 15: 101136. CrossRef
Modulation of bone turnover aberration: A target for management of primary osteoporosis in experimental rat model
Enas A. Fouad-Elhady, Hadeer A. Aglan, Rasha E. Hassan, Hanaa H. Ahmed, Gilane M. Sabry
Heliyon.2020; 6(2): e03341. CrossRef
Aromatase inhibitors attenuate the effect of alendronate in women with breast cancer
Sung Hye Kong, Jung Hee Kim, Sang Wan Kim, Chan Soo Shin
Journal of Bone and Mineral Metabolism.2020; 38(5): 730. CrossRef
Global estrogen receptor-α knockout has differential effects on cortical and cancellous bone in aged male mice
Rebecca K. Dirkes, Nathan C. Winn, Thomas J. Jurrissen, Dennis B. Lubahn, Victoria J. Vieira-Potter, Jaume Padilla, Pamela S. Hinton, Vance L. Trudeau
FACETS.2020; 5(1): 328. CrossRef
The Emerging Role of Osteocytes in Cancer in Bone
Emily G Atkinson, Jesús Delgado‐Calle
JBMR Plus.2019;[Epub] CrossRef
Effect of denosumab on low bone mineral density in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: 24-month results
Katsuhiko Nakatsukasa, Hiroshi Koyama, Yoshimi Ouchi, Hisako Ono, Kouichi Sakaguchi, Takayuki Matsuda, Makoto Kato, Takashi Ishikawa, Kimito Yamada, Mana Yoshimura, Kei Koizumi, Teruhisa Sakurai, Hideo Shigematsu, Shunji Takahashi, Shinichiro Taira, Masat
Breast Cancer.2019; 26(1): 106. CrossRef
Association of Wnt Inhibitors, Bone Mineral Density and Lifestyle Parameters in Women with Breast Cancer Treated with Anastrozole Therapy
Kristina Bojanić, Ines Bilić Ćurčić, Lucija Kuna, Tomislav Kizivat, Robert Smolic, Nikola Raguž Lučić, Kristina Kralik, Vatroslav Šerić, Gordana Ivanac, Sandra Tucak-Zorić, Aleksandar Včev, Martina Smolić
Journal of Clinical Medicine.2018; 7(9): 287. CrossRef
Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG
Peyman Hadji, Matti S. Aapro, Jean-Jacques Body, Michael Gnant, Maria Luisa Brandi, Jean Yves Reginster, M. Carola Zillikens, Claus-C. Glüer, Tobie de Villiers, Rod Baber, G. David Roodman, Cyrus Cooper, Bente Langdahl, Santiago Palacios, John Kanis, Nass
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Effects of raloxifene against letrozole-induced bone loss in chemically-induced model of menopause in mice
Abul Kalam, Sushama Talegaonkar, Divya Vohora
Molecular and Cellular Endocrinology.2017; 440: 34. CrossRef
Sclerostin: an Emerging Target for the Treatment of Cancer-Induced Bone Disease
Michelle M. McDonald, Jesus Delgado-Calle
Current Osteoporosis Reports.2017; 15(6): 532. CrossRef
Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice
Abul Kalam, Sushama Talegaonkar, Divya Vohora
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Osteoblasts Are the Centerpiece of the Metastatic Bone Microenvironment
Hyo Min Jeong, Sun Wook Cho, Serk In Park
Endocrinology and Metabolism.2016; 31(4): 485. CrossRef

Mineral, Bone & Muscle
Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis: In-Jin Cho, Ho-Yeon Chung, Sung-Woon Kim, Jae-Won Lee, Tae-Won Lee, Hye-Soon Kim, Sin-Gon Kim, Han Seok Choi, Sung-Hee Choi, Chan Soo Shin, Ki-Won Oh, Yong-Ki Min, Jung-Min Koh, Yumie Rhee, Dong-Won Byun, Yoon-Sok Chung, Jeong Hyun Park, Dong Jin Chung, Minho Shong, Eun-Gyoung Hong, Chang Beom Lee, Ki Hyun Baek, Moo-Il Kang; Endocrinol Metab. 2015;30(3):272-279. Published online December 9, 2014; DOI: https://doi.org/10.3803/EnM.2015.30.3.272

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Background

The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis.

Methods

This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period.

Results

After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment.

Conclusion

The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

Citations

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Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis
Nasrin Nasimi, Sanaz Jamshidi, Aida Askari, Nazanin Zolfaghari, Erfan Sadeghi, Mehran Nouri, Nick Bellissimo, Shiva Faghih
British Journal of Nutrition.2024; 131(9): 1473. CrossRef
Quality of life and patient satisfaction with raloxifene/cholecalciferol combination therapy in postmenopausal women
Dong-Yun Lee, Yoon-Sok Chung
Scientific Reports.2022;[Epub] CrossRef
Efficacy of risedronate with cholecalciferol on bone mineral density in Korean patients with osteoporosis
So Young Park, Moo-Il Kang, Hyung Moo Park, Yumie Rhee, Seong Hwan Moon, Hyun Koo Yoon, Jung-Min Koh, Jae Suk Chang, In Joo Kim, Ye Yeon Won, Ye Soo Park, Hoon Choi, Chan Soo Shin, Taek Rim Yoon, Sung-Cheol Yun, Ho-Yeon Chung
Archives of Osteoporosis.2020;[Epub] CrossRef
Efficacy and safety of vitamin D3 B.O.N intramuscular injection in Korean adults with vitamin D deficiency
Han Seok Choi, Yoon-Sok Chung, Yong Jun Choi, Da Hea Seo, Sung-Kil Lim
Osteoporosis and Sarcopenia.2016; 2(4): 228. CrossRef
Pharmacologic treatment of osteoporosis
Yong-Ki Min
Journal of the Korean Medical Association.2016; 59(11): 847. CrossRef

Genetic and Epigenetic Analysis in Korean Patients with Multiple Endocrine Neoplasia Type 1: Yoon Jung Chung, Sena Hwang, Jong Ju Jeong, Sun Yong Song, Se Hoon Kim, Yumie Rhee; Endocrinol Metab. 2014;29(3):270-279. Published online September 25, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.3.270

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Background

Multiple endocrine neoplasia type 1 (MEN1) is a familial syndrome characterized by the parathyroid, pancreas and pituitary tumors. Parathyroid tumors are the most common clinical manifestations, occurring in more than 90% of MEN1 patients. Heterozygous germline mutations of the MENIN gene underlie the tumorigenesis in MEN1 and epigenetic alterations along with germline mutations may contribute to tumorigenesis. Here, we investigated the associations between genotype and phenotype in Korean MEN1 patients.

Methods

We analyzed medical records from 14 unrelated MEN1 patients who had newly confirmed MENIN germline mutations, together with 14 previous reports in Korea. Aberrant DNA methylations were also examined in MEN1-related parathyroid tumors using the Infinium HumanMethylation 450 BeadChip.

Results

Total 28 germline mutations of MENIN were relatively highly concentrated in exons 7 and 8 compared to previous reports from Western countries. Six mutations (c.111dupT/p.S38Ffs^*79, c.225_226insT/p.T76Yfs^*41, c.383_398del16/p.S128Tfs^*52, c.746dupT/p.H250Afs^*20, c.1150G>T/p.E384^*, and c.1508G>A/p.G503N) were newly found in the present study. Of interest, four patients (15%) showed unusual initial presentations and three patients were diagnosed incidentally at the general medical checkup. We also found three distinct sites in exon 2 of MENIN were significantly hypomethylated in the MEN1 parathyroid tumors, comparing correspondent blood samples.

Conclusion

We also have found a lack of genotype/phenotype correlation in Korean MEN1 patients. There were not a few unusual initial manifestations in MEN1 patients, thus, genetic testing for the MENIN germline mutations can provide important information for the better prognosis. Further studies are warranted to investigate altered DNA methylations in the MENIN gene involved in tumorigenesis.

Citations

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Genotype-based prognosis prediction for MEN1-Related pancreatic neuroendocrine tumors in Korean patients a single-center retrospective study
Juwan Kim, Seung Soo Hong, Sung Hyun Kim, Ho Kyoung Hwang, Namki Hong, Yumie Rhee, Chang Moo Kang
Pancreatology.2025; 25(1): 134. CrossRef
Epidemiology and clinical outcomes of clinically suspected multiple endocrine neoplasia type 1 in South Korea: a nationwide cohort study
Kyoung Jin Kim, Min Heui Yu, Yoon-a Hwang, Shinje Moon, Namki Hong, Yumie Rhee
Frontiers in Endocrinology.2025;[Epub] CrossRef
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
Endocrinology and Metabolism.2024; 39(6): 956. CrossRef
Cutaneous lesions and other non-endocrine manifestations of Multiple Endocrine Neoplasia type 1 syndrome
Laura Pierotti, Elena Pardi, Elisa Dinoi, Paolo Piaggi, Simona Borsari, Simone Della Valentina, Chiara Sardella, Angela Michelucci, Maria Adelaide Caligo, Fausto Bogazzi, Claudio Marcocci, Filomena Cetani
Frontiers in Endocrinology.2023;[Epub] CrossRef
A Case of Asymptomatic Multiple Endocrine Neoplasia Type I with Thymic Carcinoid
Suk Ki Park, Moon Won Lee, In Sub Han, Young Joo Park, Sung Yong Han, Joon Woo Park, Bong Eun Lee, Gwang Ha Kim, Sang Soo Kim
The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2019; 19(1): 65. CrossRef
Multiple Endocrine Neoplasia Syndromes from Genetic and Epigenetic Perspectives
Fatemeh Khatami, Seyed Mohammad Tavangar
Biomarker Insights.2018;[Epub] CrossRef
Articles in 'Endocrinology and Metabolism' in 2014
Won-Young Lee
Endocrinology and Metabolism.2015; 30(1): 47. CrossRef

Case Report

1-34 PTH Could Reverse Impaired Bone Mineralization Induced By the Overdose of Bisphosphonate.: Kyeong Hye Park, Kwang Joon Kim, Han Seok Choi, Kyoung Min Kim, Eun Young Lee, Seonhui Han, Hyun Sil Kim, Daham Kim, Hannah Seok, Eun Yeong Choe, Yumie Rhee, Sung Kil Lim; Endocrinol Metab. 2012;27(3):247-250. Published online September 19, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.3.247

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Abstract PDF: Bisphosphonates are the mainstay of osteoporosis treatment. Despite the fact that bisphosphonates have a relatively good safety record and are tolerated well by the majority of patients, serious adverse events have been associated with their use. A 41-year-old man had been diagnosed with osteoporosis and had taken etidronate 200 mg/day daily for 2 years due to the judgmental error. He was referred for the management of refractory bone pain and generalized muscle ache. Serum calcium, phosphate, 25-hydroxy-vitamin D (25(OH)D), and immunoreactive parathyroid hormone (iPTH) were within normal range. Plain X-ray showed multiple fractures. Whole body bone scan confirmed multiple sites of increased bone uptakes. Tetracycline-labeled bone biopsy showed typical findings of osteomalacia. He was diagnosed with iatrogenic, etidronate-induced osteomalacia. The patient received daily parathyroid hormone (PTH) injection for 18 months. PTH effectively reverses impaired bone mineralization caused by etidronate misuse. Currently, he is doing well without bone pain. Bone mineral density significantly increased, and the increased bone uptake was almost normalized after 18 months. This case seems to suggest that human PTH (1-34) therapy, possibly in association with calcium and vitamin D, is associated with important clinical improvements in patients with impaired bone mineralization due to the side effect of bisphosphonate.

Editorial

The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change of Bone Mineral Density in Animal Model of Osteoporosis.: Yumie Rhee; Endocrinol Metab. 2011;26(4):295-296. Published online December 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.4.295

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Abstract PDF

No abstract available.

Citations

Citations to this article as recorded by

Response: The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change in Bone Mineral Density in an Animal Model of Osteoporosis
Seung Hun Lee, Jung-Min Koh, Young-Sun Lee, Beom-Jun Kim, Je-Yong Choi, Ghi-Su Kim
Endocrinology and Metabolism.2012; 27(1): 107. CrossRef

Case Report

Non-functional Pituitary Adenoma Detected on (18)F-fluorodeoxyglucose Positron Emission Tomography ((18)F-FDG-PET) in a Patient with Mucosa-associated Lymphoid Tissue Lymphoma.: Jin Ha Lee, Seung Jin Han, Se Eun Park, Mi Ae Cho, June Won Cheong, Mijin Yun, Yumie Rhee, Eun Jig Lee, Sung Kil Lim; J Korean Endocr Soc. 2008;23(2):137-141. Published online April 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.2.137

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Abstract PDF

Magnetic resonance imaging (MRI) is the modality of choice for the detection and characterization of a pituitary adenoma. Uptake of (18)F-fluorodeoxyglucose (FDG) by intrasellar tumors, including pituitary adenomas, has been reported in several previous studies. We report a case where a pituitary adenoma was detected on FDG-positron emission tomography (PET), but the tumor was not detected with the use of sellar MRI. A 31-year-old woman was referred to the clinic due to a focal increase of FDG uptake at the pituitary fossa seen on whole body FDG-PET. The patient was receiving chemotherapy due to a recurred B-cell lymphoma of the mucosa-associated lymphoid tissue type. Subsequently, sellar MRI was performed, and images showed a small non-enhancing heterogenous cystic lesion in the midline of the pituitary gland, radiologically suggestive of a Rathke's cleft cyst. However, sellar MRI failed to identify a lesion consistent with a pituitary tumor that corresponded to the site of increased FDG uptake detected by the use of PET, despite the inclusion of a dynamic contrast enhanced sequence. Despite the negative findings of the MRI examination, basal and stimulated levels of the GnRH free alpha-subunit were profoundly increased. Therefore, we suspected the presence of a non-functional pituitary tumor in addition to a Rathke's cleft cyst, rather than pituitary involvement of a lymphoma, based on the hormone levels and PET scan findings.

Citations

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Clinical Characteristics of 16 Patients with Pituitary Tumor Incidentally Detected by18F-Fluorodeoxyglucose PET-CT (18F-FDG PET-CT)
Hyung Jin Kim, Gi Jeong Cheon, A Ra Cho, Chang Hoon Lee, Sang Min Youn, Se jin Ahn, Sang Eon Jang, Jung Min Kim, Yun Yong Lee, Ka Hee Yi
Endocrinology and Metabolism.2010; 25(4): 321. CrossRef

Original Article

Identification and Validation of the Relationship of the Anabolic Effect of Parathyroid Hormone with the Wnt/beta-catenin Canonical Pathway.: Se Hwa Kim, Juan Ji An, Yumie Rhee, Sung Kil Lim; J Korean Endocr Soc. 2007;22(6):411-418. Published online December 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.6.411

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Abstract PDF

BACKGROUND
It has been well established that daily injections of low dose parathyroid hormone (PTH) increase bone mass in animals and humans. However, the precise mechanisms by which PTH exerts its anabolic action on bone are incompletely understood. The canonical Wnt-b-catenin signaling pathway has recently been demonstrated to have an important role in bone cell function. In the present study, we have examined the interaction between the PTH and Wnt signaling pathways in mouse osteoblastic MC3T3-E1 cells. METHODS & RESULTS: MC3T3-E1 cells were treated with 0.01-0.84 micrometer recombinant PTH. beta-catenin expression was significantly increased after 30 minutes of exposure to PTH and reached a maximum 2.7 fold increase at 1 hr and expression then faded at 6 hrs. In addition, treatment with PTH increased nuclear accumulation of activated beta-catenin; the ratio between the nuclear to cytoplasmic protein was more than three fold at 30 minutes and beyond. Moreover, PTH stimulated T-cell factor/lymphoid enhancer factor (TCF/LEF) reporter gene activity in MC3T3-E1 cells. Confocal microscopy revealed nuclear translocation of beta-catenin by PTH as compared with a glycogen synthase kinase-3beta (GSK-3beta) inhibitor. CONCLUSION: These results suggest that the anabolic mechanism of PTH might be partially associated with the Wnt-canonical pathway. The appropriate target of another anabolic agent should be determined through further studies of this pathway.

Citations

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Effects of N-acetyl-l-cysteine on fish hepatoma cells treated with mercury chloride and ionizing radiation
Jin Kyu Kim, Min Han, Mohammad Nili
Chemosphere.2011; 85(10): 1635. CrossRef
Bone Forming Effect of PTH through Wnt/β-catenin Signaling System
Dong Jin Chung, Min Young Chung
Journal of Korean Endocrine Society.2007; 22(6): 407. CrossRef

Case Reports

A Case of Familial Hypocalciuric Hypercalcemia Coexisting with Low Bone Mass.: Sung Wan Chun, Se Hwa Kim, Jong Yul Jung, Won Na Suh, Ji Ae Moon, Jong In Yook, Yoon Sok Chung, Yumie Rhee, Eun Jig Lee, Sung Kil Lim; J Korean Endocr Soc. 2006;21(6):583-588. Published online December 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.6.583

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Abstract PDF: Familial hypocalciuric hypercalcemia is caused by heterozygous loss-of-function mutation of the calcium sensing receptor gene, and this is characterized by mild, persistently elevated levels of serum calcium without symptoms or complications. We present a case of clinically diagnosed familial hypocalciuric hypercalcemia with unexpected low bone mass. A 19-year-old man presented with incidentally discovered hypercalcemia. He showed normal growth and sexual maturation. Biochemical studies showed hypercalcemia, increased parathyroid hormone, hypocalciuria, a decreased urinary calcium-creatinine ratio and decreased serum 25-hydroxy-vitamin D. The other hormonal studies were normal. Dual energy x-ray absorptiometry showed low bone mineral density, and the Sestamibi scan showed no abnormality in the parathyroid glands. Iliac bone biopsy showed a general decrease in bone density and increased porosity of the cortical bone. Normal mineralization was also shown, but in part, osteoid deposition was also found. Direct sequencing of the patient's calcium sensing receptor gene showed a point mutation at exon7, Q926R.

A Case of Autoimmune Hypoglycemia due to Insulin Antibody in Patient with End Stage Renal Disease.: Ji Ye Jung, Eun Seok Kang, Beom Seok Kim, Sung Wan Chun, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Hyun Chul Lee; J Korean Endocr Soc. 2006;21(6):536-541. Published online December 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.6.536

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Abstract PDF: Fasting hypoglycemia results from several mechanisms. Autoimmune hypoglycemia is one of the rare causes of hypoglycemia, and characterized by hyperinsulinemia, fasting hypoglycemia and the presence of autoantibodies to insulin or insulin receptor. We report here on a 64-year-old male patient with autoimmune hypoglycemia with end stage renal disease. He had no history of diabetes or insulin use. He had experienced several severe hypoglycemic events. The serum C-peptide level was 7.48 ng/mL and the insulin concentration was 115.4 micro U/mL when the fasting plasma glucose level was 88 mg/dL. The insulin to glucose ratio was 5.42, which suggested the presence of insulinoma. Yet the radiologic studies, including magnetic resonance cholangiopancreatography, endoscopic ultrasonography and selective calcium stimulated venous sampling revealed no evidence of insulinoma. The insulin autoantibody level was 62 micro U/mL. Therefore, we could diagnosis the autoimmune hypoglycemia. The hypoglycemia was treated with prednisolone and the patient recovered from this. His insulin level decreased to 21.11 micro U/mL and the insulin autoantibody level decreased to 34 micro U/mL. Hypoglycemia in the hemodialysis patients is not uncommon. One should bear in mind autoimmune hypoglycemia as one of the causes of hypoglycemia in patients with no history of diabetes.

Original Articles

Effect of Sequential Therapy with Incadronate after Withdrawal of Recombinant Human Parathyroid Hormone(1-84) on Bone Quantity and Quality in Ovariectomized Rats.: Yumie Rhee, Jong Chan Youn, Ye Yeon Won, Myong Hyun Baek, Sung Kil Lim; J Korean Endocr Soc. 2005;20(4):334-343. Published online August 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.4.334

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Abstract PDF: BACKGROUND
Human parathyroid hormone(hPTH) is a promising anabolic agent. However, since hPTH (1-34) is available only via injection, and has a critical side effect of causing bone tumors during life-long administration in the rat, it would be practical to use PTH for the shortest possible duration to obtain the maximal effect. In addition, acquired bone mass due to hPTH tend to decrease after drug cessation. To determine the effectiveness of the osteoporosis-reversing concept of lose, restore, and maintain(LRM), recombinant human PTH(1-84)[rhPTH(1-84)] and the respective anti-resorptive agents were sequentially studied. METHODS: Thirty six, 20-week-old, Sprague-Dawley rats were used in this study. Treatment was started on the 25th week after an ovariectomy, which had been performed at 20weeks of age, with 5weeks of rhPTH (1-84) 100(microgram/kg/d), 5days/wk, followed by the respective sequential therapies for 5 weeks as follows: 1) Ovariectomized rats(OVX, n=6), 2) Sham operated rats(SHAM, n=6), 3) OVX rats with PTH maintenance(PTH-M, n=6), 4) OVX rats treated with PTH then withdrawn(PTH-W, n=6), 5) PTH-treated OVX rats then treated with 17beta-estradiol(PTH-E, 10microgram/d, SQ, 5days/wk, n=6), 6) PTH-treated OVX rats then treated with incadronate(PTH-I, 3mg/kg, per os 5 days/wk, n=6). The bone mineral density(BMD) of the right femurs was measured using dual X-ray absorptiometry(DXA). Microcomputed tomography(microCT) was used to measure the structural parameters of the 2nd lumbar vertebrae. A three-point bending test of the femur and compressive tests of vertebrae were also performed. RESULTS: Bone quantity data showed that the femoral BMD was significantly higher in the PTH-M and PTH-I groups than in the OVX and PTH-W groups(P<0.05). Measurement of the cortical thickness revealed that only the PTH-M group had a significant increase(P=0.001). The ultimate force(Fu) at the midshaft of the femur was stronger in the PTH-M group than in the OVX group(P<0.001). However, no significant difference was found among the treated groups. CONCLUSION: PTH withdrawal resulted in the loss of the acquired BMD, but sequential therapy with the anti-resorptive, incadronate, prevented further bone loss. The use of incadronate after rhPTH(1-84), as a sequential regimen, was significantly effective on the maintenance in the bone mass, but further clarification in the improvement in the bone quality is needed.

The Effect of Treatment Modalities on Survival Rates of Patients with Anaplastic Thyroid Carcinoma.: Jae Myoung Choi, Mi Jeong Kim, Seung Won Lee, Kyoung Eun Song, Yoon Sok Chung, Kwan Woo Lee, Dae Jung Kim, Sung Hee Choi, So Hun Kim, Min Ho Cho, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim; J Korean Endocr Soc. 2005;20(2):127-133. Published online April 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.2.127

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Abstract PDF

BACKGROUND
Anaplastic thyroid carcinoma represents 2% to 5% of all thyroid cancers and it is one of the most aggressive human cancers. Local extension at the time of diagnosis and distant metastases are almost always the rule. Its lethality is evidenced by a 5-year survival rate of 3.6% and a median survival time of 4 months. We retrospectively reviewed patients with this disease at 4 tertiary referral centers. METHODS: From 1990 to 2003, 19 cases(9 men and 10 women, mean age: 65.1+/-7.1 years) of anaplastic thyroid carcinoma were reviewed via the medical records. The overall survival rates according to the prognostic factors and the treatment modalities were analyzed. RESULTS: The presenting symptoms included rapidly enlarged neck masses in 16 patients, shortness of breath in 3 patients, hoarseness in 4 patients, dysphagia in 2 patients and chest wall pain in 1 patient. The mean diameter of tumor was 7.2cm. Local extension was seen in all of the cases that had undergone surgery. Distant metastases(lung 6, bone 2, abdominal carcinomatosis 2, brain 1 and mediastinum 1) were seen in 9 patients. Surgical treatment was performed in 10 patients. Radiotherapy was performed in 9 patients and chemotherapy was done in 5 patients; radiotherapy was performed alone in 2 patients, combination chemo-radiotherapy was performed in 3 patients, postoperative radiotherapy was performed in 2 patients and postoperative combination chemo-radiotherapy was performed in 2 patients. 4 patients were treated cons ervatively after the confirmative diagnosis. The overall median survival time was 123 days(range: 23~621 days); the median survival time was 129 days in the treatment group(n=15), and 27 days in the no treatment group (n=4), and significantly higher survival rates were observed for the treated patients(p=0.02). According to the treatment modalities, patients who underwent surgical treatment and postoperative radiotherapy and/or chemotherapy were observed to have significantly higher survival rates than patients in the radiotherapy and/or chemotherapy group(p=0.03), and also than those patients in the surgical treatment only group(p=0.04). CONCLUSION: We found that aggressive surgical treatment and postoperative radiotherapy and/or chemotherapy improved the survival rates of patients with anaplastic thyroid carcinoma even though local invasion and distant metastases was generally observed to occur

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Anaplastic Thyroid Carcinoma: Experience of a Single Institute
Dongbin Ahn, Jin Ho Sohn
Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2012; 55(1): 37. CrossRef

Androgen and Cardiovascular Disease.: Yumie Rhee; J Korean Endocr Soc. 2004;19(6):583-591. Published online December 1, 2004

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Abstract PDF: Np abstract available.

Case Report

A Case of Thyroid Papillary Cancer Associated with Familial Adenomatous Polyposis.: Sung Jae Shin, Hyun Joo Lee, So Hun Kim, Wan Sub Shim, Sihoon Lee, Yoo Mee Kim, Yumie Rhee, Tae Il Kim, Bong Soo Cha, Hyun Chul Lee, Sung Kil Lim; J Korean Endocr Soc. 2004;19(2):209-216. Published online April 1, 2004

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Abstract PDF: Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome, typically characterized by multiple colorectal adenomas and increased incidence of colorectal carcinomas if left untreated. It is caused by germline mutations of the adenomatous polyposis coli (APC) gene, which has been mapped on chromosome 5q21, and is accompanied by various benign and malignant extracolonic manifestations. The prevalence of thyroid tumors developing in patients with FAP is about 1~2%, are associated with FAP and have certain characteristics; mean age of tumor diagnosis at less than 30 years of age, the pathology is the papillary histiotype in more than 90% of cases, including a so-called cribriform- morular pattern, and multifocality is a frequent feature. In a genetic analysis, thyroid cancer in FAP usually has a mutation in the 5-portion of exon 15 between 778 and 1309, on chromosome 5q21. Also, the ret/PTC (especially ret/PTC1 and ret/PTC3) and p53 genes are thought probably to be associated with thyroid cancer in FAP patients. A case of familial adenomatous polyposis, accompanied by thyroid papillary cancer, was experienced in a 29 year-old female. She had hundreds of adenomas throughout the entire colon and congenital hypertrophy of the retinal pigment epithelium (CHRPE). The pathological finding of thyroid cancer was revealed as a mixture of cribriform, trabecular and papillary patterns. In a genetic analysis, she and her brother had a germline mutation of the APC gene at codon 1309. In Korea, there has been no previous case of cribriform-morular pattern and familial genetic analysis in FAP associated with thyroid cancer. Therefore, this case is reported, with a review of the literature

Original Article

Association between Serum Leptin Concentration and Bone Mineral Density in Healthy Korean Women.: Yumie Rhee, Dae Jung Kim, Se Hwa Kim, Chul Woo Ahn, Bong Soo Cha, Kyung Rae Kim, Hyun Chul Lee, Sung Kil Lim; J Korean Endocr Soc. 2003;18(2):177-183. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Leptin is known to affect bone metabolism both centrally and peripherally. This study was performed to investigate the relationship between leptin and bone mineral density(BMD) in healthy premenopausal and postmenopausal Korean women. METHODS: 140 women were recruited for a routine health check-up. Anthro-pometric and biochemical data were checked as usual. BMDs were measured by dual x-ray absorptiometry of the spine and femur in 67 premenopausal women and 73 postmenopausal women, in addition to their serum leptin levels. RESULTS: Serum leptin level showed no correlation with BMD in premenopausal women, but there was a positive correlation betwen serum leptin and spinal BMD in postmenopausal women(r=0.468, p<0.001). After the correcting for age, body mass index, and duration of menopause, the serum leptin level and BMD still showed a positive correlation(r=0.217, p=0.088) although weak. The women in the lowest quartile of serum leptin level showed significantly lower lumbar and femoral neck BMD. CONCLUSION: Leptin level seems to have a weak relationship with BMD showing different features in premenopausal and postmenopausal women.

Case Report

A Case of Propylthiouracil Induced Anti: Neutrophil Cytoplasmic Antibody (ANCA) Positive Vasculitis.: Yumie Rhee, Sang Su Chung, Su Youn Nam, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; J Korean Endocr Soc. 1999;14(4):757-763. Published online January 1, 2001

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Abstract PDF: A 40-year-old woman just had started to take propylthiouracil for Graves disease, However, the treatment had to be interrupted because she developed skin rash, arthritis, chest pain, fever and proteinuria after 2 months. The serologic study revealed antineutrophil cytoplasmic antibody(ANCA) positivity, especially showing perinuclear pattern. The anti-myeloperoxidase titer was high. The hematoxylin & eosin stain of the specimen obtained from kidney was compatible with pauci-immune glomerulonephritis with crescent formation. There were no immune complex deposits under electron microscope. Such findings suggested propylthiouracil-induced vasculitis. Vasculitis is a rare side effect of propylthiouracil. Recently more cases of vasculitis associated with anti-thyroid drug with ANCA positivity are being reported up to about 36 cases worldwide. There are possibilities of underdiagnosis of this side effect, meaning more cautions on the patients under anti-thyroid drug treatment. We present a case with review of related literature.

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