Endocrinology and Metabolism

Original Article

Calcium & bone metabolism
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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Abstract PDF Supplementary Material PubReader ePub: 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.

Review Article

Calcium & Bone Metabolism
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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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
A Rare Case of Hyperfunctioning Lipoadenoma Presenting as a Cystic Pararthyroid Lesion
Jinyoung Kim, Ohjoon Kwon, Tae-Jung Kim, So Lyung Jung, Eun Ji Han, Ki-Ho Song
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
Medicina.2023; 60(1): 15. CrossRef
Diagnostic Performance of Magnetic Resonance Imaging for Parathyroid Localization of Primary Hyperparathyroidism: A Systematic Review
Max H. M. C. Scheepers, Zaid Al-Difaie, Lloyd Brandts, Andrea Peeters, Bjorn Winkens, Mahdi Al-Taher, Sanne M. E. Engelen, Tim Lubbers, Bas Havekes, Nicole D. Bouvy, Alida A. Postma
Diagnostics.2023; 14(1): 25. CrossRef

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.

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Impaired Melatonin Secretion, Oxidative Stress and Metabolic Syndrome in Night Shift Work
Sorina Hohor, Cristina Mandanach, Andreea Maftei, Corina Aurelia Zugravu, Marina Ruxandra Oțelea
Antioxidants.2023; 12(4): 959. CrossRef
Normal-Weight Obesity and Metabolic Syndrome in Korean Adults: A Population-Based Cross-Sectional Study
Jeonghyeon Kim, Seamon Kang, Hyunsik Kang
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You Can’t Avoid Shift Work? Then Focus on Body Fat Rather than Weight
Eun Kyung Lee
Endocrinology and Metabolism.2022; 37(5): 756. CrossRef

Calcium & Bone Metabolism
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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Prevalence of denosumab-induced hypocalcemia: a retrospective observational study of patients routinely monitored with ionized calcium post-injection
Anna Spångeus, Johan Rydetun, Mischa Woisetschläger
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Cost-consequence analysis of continuous denosumab therapy for osteoporosis treatment in South Korea
Seungju Cha, Minjeong Sohn, Hyowon Yang, Eric J. Yeh, Ki-Hyun Baek, Jeonghoon Ha, Hyemin Ku
BMC Musculoskeletal Disorders.2024;[Epub] CrossRef
Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis
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Adverse Effects of Denosumab in Kidney Transplant Recipients: A 20-Year Retrospective Single-Center Observation Study in Central Taiwan
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Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study
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Endocrinology and Metabolism.2023; 38(2): 260. CrossRef
Effect of Denosumab on Bone Density in Postmenopausal Osteoporosis: A Comparison with and without Calcium Supplementation in Patients on Standard Diets in Korea
Chaiho Jeong, Jinyoung Kim, Jeongmin Lee, Yejee Lim, Dong-Jun Lim, Ki-Hyun Baek, Jeonghoon Ha
Journal of Clinical Medicine.2023; 12(21): 6904. CrossRef
Denosumab

Reactions Weekly.2022; 1919(1): 221. CrossRef
Denosumab, an effective osteoporosis treatment option for men
Sung Hye Kong
The Korean Journal of Internal Medicine.2022; 37(5): 947. CrossRef

Calcium & Bone Metabolism
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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A review of radiological definitions of sarcopenia in cancer
James W. Wang, Jiarong Chen, Alison H. McGregor, Matthew Williams
JCSM Clinical Reports.2023; 8(2): 36. CrossRef
Weight‐adjusted waist as an integrated index for fat, muscle and bone health in adults
Kyoung Jin Kim, Serhim Son, Kyeong Jin Kim, Sin Gon Kim, Nam Hoon Kim
Journal of Cachexia, Sarcopenia and Muscle.2023; 14(5): 2196. CrossRef

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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Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks
Nathan Mullen, James Curneen, Padraig T Donlon, Punit Prakash, Irina Bancos, Mark Gurnell, Michael C Dennedy
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Steroid profiling in adrenal disease
Danni Mu, Dandan Sun, Xia Qian, Xiaoli Ma, Ling Qiu, Xinqi Cheng, Songlin Yu
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Serum and hair steroid profiles in patients with nonfunctioning pituitary adenoma undergoing surgery: A prospective observational study
Seung Shin Park, Yong Hwy Kim, Ho Kang, Chang Ho Ahn, Dong Jun Byun, Man Ho Choi, Jung Hee Kim
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LC-MS based simultaneous profiling of adrenal hormones of steroids, catecholamines, and metanephrines
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2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
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Prevalence and Characteristics of Adrenal Tumors in an Unselected Screening Population
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Annals of Internal Medicine.2022; 175(10): 1383. CrossRef

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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A Prospective Comparative Study of 18F-FDOPA PET/CT Versus 123I-MIBG Scintigraphy With SPECT/CT for the Diagnosis of Pheochromocytoma and Paraganglioma
Changhwan Sung, Hyo Sang Lee, Dong Yun Lee, Yong-il Kim, Jae Eun Kim, Sang Ju Lee, Seung Jun Oh, Tae-Yon Sung, Yu-Mi Lee, Young Hoon Kim, Beom-Jun Kim, Jung-Min Koh, Seung Hun Lee, Jin-Sook Ryu
Clinical Nuclear Medicine.2024; 49(1): 27. CrossRef
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association
A Ram Hong, Ho-Cheol Kang
Endocrinology and Metabolism.2023; 38(2): 175. CrossRef
Lesion-based indicators predict long-term outcomes of pheochromocytoma and paraganglioma– SIZEPASS
Helena Hanschell, Salvador Diaz-Cano, Alfredo Blanes, Nadia Talat, Gabriele Galatá, Simon Aylwin, Klaus Martin Schulte
Frontiers in Endocrinology.2023;[Epub] CrossRef
Interleukin-6-producing paraganglioma as a rare cause of systemic inflammatory response syndrome: a case report
Yin Young Lee, Seung Min Chung
Journal of Yeungnam Medical Science.2023; 40(4): 435. CrossRef
(Extremely rare intrapericardial location of paraganglioma)
Jaroslav Zajíc, Aleš Mokráček, Ladislav Pešl, Jiří Haniš, Dita Schaffelhoferová
Cor et Vasa.2023; 65(4): 692. CrossRef
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Naoki Okada, Akihiro Shioya, Sumihito Togi, Hiroki Ura, Yo Niida
Cureus.2023;[Epub] CrossRef
KSNM60 in Nuclear Endocrinology: from the Beginning to the Future
Chae Moon Hong, Young Jin Jeong, Hae Won Kim, Byeong-Cheol Ahn
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Change of Computed Tomography-Based Body Composition after Adrenalectomy in Patients with Pheochromocytoma
Yousun Ko, Heeryoel Jeong, Seungwoo Khang, Jeongjin Lee, Kyung Won Kim, Beom-Jun Kim
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Evaluation and Management of Bone Health in Patients with Thyroid Diseases: a Position Statement from the Korean Thyroid Association
A Ram Hong, Hwa Young Ahn, Bu Kyung Kim, Seong Hee Ahn, So Young Park, Min-Hee Kim, Jeongmin Lee, Sun Wook Cho, Ho-Cheol Kang
International Journal of Thyroidology.2022; 15(1): 1. CrossRef
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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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Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma
Susan Richter, Nicole Bechmann
Journal of the Endocrine Society.2024;[Epub] CrossRef
Novel and recurrent genetic variants of VHL, SDHB, and RET genes in Chinese pheochromocytoma and paraganglioma patients
Chong Li, Jingyi Li, Chao Han, Ting Wang, Lixia Zhang, Zhifang Wang, Tingting Wang, Lijun Xu, Guangzhao Qi, Guijun Qin, Xialian Li, Lili Zheng
Frontiers in Genetics.2023;[Epub] CrossRef
Genetic Study in Pheochromocytoma: Is It Possible to Stratify the Risk of Hereditary Pheochromocytoma?
Marta Araujo-Castro, César Mínguez Ojeda, Iñigo García Sanz, Maria Calatayud, Felicia Hanzu, Mireia Mora, Almudena Vicente, Concepción Blanco Carrera, Paz de Miguel Novoa, María del Carmen López García, Cristina Lamas, Laura Manjón-Miguélez, María del Cas
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Bilateral Pheochromocytoma with Germline MAX Variant without Family History
Shinnosuke Hata, Mai Asano, Hiroyuki Tominaga, Masahide Hamaguchi, Fumiya Hongo, Takeshi Usui, Eiichi Konishi, Michiaki Fukui
Clinics and Practice.2022; 12(3): 299. CrossRef
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
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Prevalence of Germline Variants in a Large Cohort of Japanese Patients with Pheochromocytoma and/or Paraganglioma
Masato Yonamine, Koichiro Wasano, Yuichi Aita, Takehito Sugasawa, Katsutoshi Takahashi, Yasushi Kawakami, Hitoshi Shimano, Hiroyuki Nishiyama, Hisato Hara, Mitsuhide Naruse, Takahiro Okamoto, Tadashi Matsuda, Shinji Kosugi, Kazuhiko Horiguchi, Akiyo Tanab
Cancers.2021; 13(16): 4014. CrossRef
Recurrent Germline Mutations of CHEK2 as a New Susceptibility Gene in Patients with Pheochromocytomas and Paragangliomas
Yinjie Gao, Chao Ling, Xiaosen Ma, Huiping Wang, Yunying Cui, Min Nie, Anli Tong, Dario De Biase
International Journal of Endocrinology.2021; 2021: 1. CrossRef

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.

Citations

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Artificial Intelligence for Predicting and Diagnosing Complications of Diabetes
Jingtong Huang, Andrea M. Yeung, David G. Armstrong, Ashley N. Battarbee, Jorge Cuadros, Juan C. Espinoza, Samantha Kleinberg, Nestoras Mathioudakis, Mark A. Swerdlow, David C. Klonoff
Journal of Diabetes Science and Technology.2023; 17(1): 224. CrossRef
Expressions of Cushing’s syndrome in multiple endocrine neoplasia type 1
William F. Simonds
Frontiers in Endocrinology.2023;[Epub] CrossRef
Application of machine learning and artificial intelligence in the diagnosis and classification of polycystic ovarian syndrome: a systematic review
Francisco J. Barrera, Ethan D.L. Brown, Amanda Rojo, Javier Obeso, Hiram Plata, Eddy P. Lincango, Nancy Terry, René Rodríguez-Gutiérrez, Janet E. Hall, Skand Shekhar
Frontiers in Endocrinology.2023;[Epub] CrossRef
Predictors of rituximab effect on modified Rodnan skin score in systemic sclerosis: a machine-learning analysis of the DesiReS trial
Satoshi Ebata, Koji Oba, Kosuke Kashiwabara, Keiko Ueda, Yukari Uemura, Takeyuki Watadani, Takemichi Fukasawa, Shunsuke Miura, Asako Yoshizaki-Ogawa, Asano Yoshihide, Ayumi Yoshizaki, Shinichi Sato
Rheumatology.2022; 61(11): 4364. CrossRef
Automating and improving cardiovascular disease prediction using Machine learning and EMR data features from a regional healthcare system
Qi Li, Alina Campan, Ai Ren, Wael E. Eid
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Rosy Oh, Hong Kyu Lee, Youngmi Kim Pak, Man-Suk Oh
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Ensemble blood glucose prediction in diabetes mellitus: A review
M.Z. Wadghiri, A. Idri, Touria El Idrissi, Hajar Hakkoum
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The maze runner: navigating through basic kinetics to AI models of human metabolism pathology
Arina V. Martyshina, Oksana M. Tilinova, Anastasia A. Simanova, Olga S. Knyazeva, Irina V. Dokukina
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Applications of Machine Learning in Bone and Mineral Research
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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

Citations to this article as recorded by

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

Citations to this article as recorded by

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.

Citations

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Association of gamma-glutamyl transferase variability with risk of osteoporotic fractures: A nationwide cohort study
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Scientific Reports.2022;[Epub] CrossRef
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