Endocrinology and Metabolism

Original Article

Comparison of the Effectiveness and Hypocalcemia Risk of Antiresorptive Agents in Patients with Hypercalcemia of Malignancy: Sung Hye Kong, Seung Shin Park, Jung Hee Kim, Sang Wan Kim, Se Hyun Kim, Jee Hyun Kim, Chan Soo Shin; Received August 2, 2024 Accepted October 29, 2024 Published online February 4, 2025; DOI: https://doi.org/10.3803/EnM.2024.2132 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Hypercalcemia of malignancy (HCM), a major metabolic complication of cancer, is often managed with bisphosphonates (BP) and, increasingly, with denosumab. We aimed to compare the effectiveness and safety of denosumab with that of BP, with or without calcitonin, in treating HCM.
Methods
This retrospective cohort study was conducted at a tertiary hospital from 2017 to 2022 and included 317 patients treated for HCM. Participants were divided into three treatment groups: denosumab, intravenous (IV) BP only, and IV BP combined with calcitonin. The primary outcomes measured were changes in calcium levels and the incidence of hypocalcemia. Analysis of covariance was used to adjust for age, sex, body mass index, creatinine level, type of malignancy, and the use of furosemide and steroids.
Results
The mean participant age was 65 years, and 37.5% were female. After adjustment, both denosumab and IV BPs were found to effectively lower calcium levels. Denosumab led to a decrease of 2.0 mg/dL (−15.9%), while IV BP alone resulted in a reduction of 1.8 mg/dL (−13.9%). The largest reduction, of 2.7 mg/dL (−20.9%), occurred with IV BP and calcitonin. Both denosumab and IV BP+calcitonin yielded their lowest calcium levels within 48 hours, whereas the IV BP only group reached a nadir within 72 hours. Despite these differences in treatment effectiveness, hypocalcemia occurred significantly less frequently in the denosumab group compared to the other groups.
Conclusion
Denosumab and IV BP were similarly effective in reducing calcium levels. However, IV BP combined with calcitonin yielded a more rapid and pronounced decrease.

Review Articles

Calcium & bone metabolism
Effects of Endocrine-Disrupting Chemicals on Bone Health: So Young Park, Sung Hye Kong, Kyoung Jin Kim, Seong Hee Ahn, Namki Hong, Jeonghoon Ha, Sihoon Lee, Han Seok Choi, Ki-Hyun Baek, Jung-Eun Kim, Sang Wan Kim, on Behalf of Metabolic Bone Disease Study Group of Korean Endocrine Society; Endocrinol Metab. 2024;39(4):539-551. Published online July 17, 2024; DOI: https://doi.org/10.3803/EnM.2024.1963

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This comprehensive review critically examines the detrimental impacts of endocrine-disrupting chemicals (EDCs) on bone health, with a specific focus on substances such as bisphenol A (BPA), per- and polyfluoroalkyl substances (PFASs), phthalates, and dioxins. These EDCs, by interfering with the endocrine system’s normal functioning, pose a significant risk to bone metabolism, potentially leading to a heightened susceptibility to bone-related disorders and diseases. Notably, BPA has been shown to inhibit the differentiation of osteoblasts and promote the apoptosis of osteoblasts, which results in altered bone turnover status. PFASs, known for their environmental persistence and ability to bioaccumulate in the human body, have been linked to an increased osteoporosis risk. Similarly, phthalates, which are widely used in the production of plastics, have been associated with adverse bone health outcomes, showing an inverse relationship between phthalate exposure and bone mineral density. Dioxins present a more complex picture, with research findings suggesting both potential benefits and adverse effects on bone structure and density, depending on factors such as the timing and level of exposure. This review underscores the urgent need for further research to better understand the specific pathways through which EDCs affect bone health and to develop targeted strategies for mitigating their potentially harmful impacts.

Citations

Citations to this article as recorded by

Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking
Xiao Zhang, Xi Zhu, Wenbo Gu, Xusheng Li, Tenyao Niu, Pengcheng Mao, Haifeng Yuan
Ecotoxicology and Environmental Safety.2025; 291: 117820. CrossRef

Calcium & bone metabolism
Bone Loss after Solid Organ Transplantation: A Review of Organ-Specific Considerations: Kyoung Jin Kim, Jeonghoon Ha, Sang Wan Kim, Jung-Eun Kim, Sihoon Lee, Han Seok Choi, Namki Hong, Sung Hye Kong, Seong Hee Ahn, So Young Park, Ki-Hyun Baek, on Behalf of Metabolic Bone Disease Study Group of Korean Endocrine Society; Endocrinol Metab. 2024;39(2):267-282. Published online April 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.1939

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This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

Citations

Citations to this article as recorded by

Romosozumab as Treatment for Severe Osteoporosis in Heart and Lung Transplant Recipients
Lisa M. Raven, Jacqueline R. Center, Christopher A. Muir
Endocrines.2025; 6(1): 2. CrossRef

Original Article

Calcium & bone metabolism
Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality: Sung Hye Kong, Jeong Mo Bae, Jung Hee Kim, Sang Wan Kim, Dohyun Han, Chan Soo Shin; Endocrinol Metab. 2024;39(2):375-386. Published online March 21, 2024; DOI: https://doi.org/10.3803/EnM.2023.1827

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Abstract PDF Supplementary Material PubReader ePub: Background
Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses.
Methods
We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis.
Results
The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations.
Conclusion
Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.

Response

Adrenal Gland
Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism (Endocrinol Metab 2021;36:875-84, Ye Seul Yang et al.): Ye Seul Yang, Sang Wan Kim; Endocrinol Metab. 2022;37(6):953-954. Published online December 12, 2022; DOI: https://doi.org/10.3803/EnM.2022.603

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Original Articles

Calcium & Bone Metabolism
Effect of Vitamin D Supplementation on Risk of Fractures and Falls According to Dosage and Interval: A Meta-Analysis: Sung Hye Kong, Han Na Jang, Jung Hee Kim, Sang Wan Kim, Chan Soo Shin; Endocrinol Metab. 2022;37(2):344-358. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1374

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Background
Although recent studies comparing various dosages and intervals of vitamin D supplementation have been published, it is yet to be elucidated whether there is an appropriate dose or interval to provide benefit regarding fracture risk. We aimed to assess the published evidence available to date regarding the putative beneficial effects of vitamin D supplements on fractures and falls according to various dosages and intervals.
Methods
We performed a meta-analysis of randomized controlled studies reporting associations between vitamin D supplementation and the risks of fractures and falls in PubMed, EMBASE, and Cochrane library. Studies with supplements of ergocalciferol or calcitriol, those with a number of event ≤10, or those with a follow-up duration of less than 6 months were also excluded.
Results
Thirty-two studies were included in the final analysis. Vitamin D supplementation with daily dose of 800 to 1,000 mg was associated with lower risks of osteoporotic fracture and fall (pooled relative risk [RR], 0.87; 95% confidence interval [CI], 0.78 to 0.97 and RR, 0.91; 95% CI, 0.85 to 0.98), while studies with <800 or >1,000 mg/day did not. Also, among intervals, daily administration of vitamin D was associated with the reduced risk of falls, while intermittent dose was not. Also, patients with vitamin D deficiency showed a significant risk reduction of falls after vitamin D supplementation.
Conclusion
Daily vitamin D dose of 800 to 1,000 IU was the most probable way to reduce the fracture and fall risk. Further studies designed with various regimens and targeted vitamin D levels are required to elucidate the benefits of vitamin D supplements.

Citations

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Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 µg) of Vitamin D for Adults in the General Population
Pawel Pludowski, William B. Grant, Spyridon N. Karras, Armin Zittermann, Stefan Pilz
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Clinical Characteristics and Outcomes of Limb Fractures in Saudi Children
Lamia Aldhbiban, Fai Alhoshan, Raghad Alomari, Shahad A Almatrafi, Yousef Alanazi, Samir Alsayegh, Haifa Y Alfaraidi, Ayman H Jawadi, Fahad N Aljuraibah
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Adrenal Gland
Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism: Jung Hee Kim, Chang Ho Ahn, Su Jin Kim, Kyu Eun Lee, Jong Woo Kim, Hyun-Ki Yoon, Yu-Mi Lee, Tae-Yon Sung, Sang Wan Kim, Chan Soo Shin, Jung-Min Koh, Seung Hun Lee; Endocrinol Metab. 2022;37(2):369-382. Published online April 14, 2022; DOI: https://doi.org/10.3803/EnM.2022.1391

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

Citations

Citations to this article as recorded by

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

Corrigendum

Miscellaneous
Corrigendum: Correction of Acknowledgments. Transformation of Mature Osteoblasts into Bone Lining Cells and RNA Sequencing-Based Transcriptome Profiling of Mouse Bone during Mechanical Unloading: A Ram Hong, Kwangsoo Kim, Ji Yeon Lee, Jae-Yeon Yang, Jung Hee Kim, Chan Soo Shin, Sang Wan Kim; Endocrinol Metab. 2021;36(6):1314. Published online November 18, 2021; DOI: https://doi.org/10.3803/EnM.2021.601; Corrects: Endocrinol Metab 2020;35(2):456

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Original Article

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.

Citations

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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
Endocrine Reviews.2024; 45(1): 125. CrossRef
Steroid profiling in adrenal disease
Danni Mu, Dandan Sun, Xia Qian, Xiaoli Ma, Ling Qiu, Xinqi Cheng, Songlin Yu
Clinica Chimica Acta.2024; 553: 117749. CrossRef
Plasma Steroid Profiling Combined With Machine Learning for the Differential Diagnosis in Mild Autonomous Cortisol Secretion From Nonfunctioning Adenoma in Patients With Adrenal Incidentalomas
Danni Mu, Xia Qian, Yichen Ma, Xi Wang, Yumeng Gao, Xiaoli Ma, Shaowei Xie, Lian Hou, Qi Zhang, Fang Zhao, Liangyu Xia, Liling Lin, Ling Qiu, Jie Wu, Songlin Yu, Xinqi Cheng
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Mild autonomous cortisol secretion: pathophysiology, comorbidities and management approaches
Alessandro Prete, Irina Bancos
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Yui Nakano, Maki Yokomoto-Umakoshi, Kohta Nakatani, Hironobu Umakoshi, Hiroshi Nakao, Masamichi Fujita, Hiroki Kaneko, Norifusa Iwahashi, Tatsuki Ogasawara, Tazuru Fukumoto, Yayoi Matsuda, Ryuichi Sakamoto, Yoshihiro Izumi, Takeshi Bamba, Yoshihiro Ogawa
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Jin Gyeong Son, Hyun Kyong Shon, Ji-Eun Kim, In−Ho Lee, Tae Geol Lee
Journal of the American Society for Mass Spectrometry.2024; 35(12): 3107. CrossRef
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
The Journal of Steroid Biochemistry and Molecular Biology.2023; 230: 106276. CrossRef
Recent Updates on the Management of Adrenal Incidentalomas
Seung Shin Park, Jung Hee Kim
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LC-MS based simultaneous profiling of adrenal hormones of steroids, catecholamines, and metanephrines
Jongsung Noh, Chaelin Lee, Jung Hee Kim, Seung Woon Myung, Man Ho Choi
Journal of Lipid Research.2023; 64(11): 100453. CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
Endocrinology and Metabolism.2023; 38(6): 597. CrossRef
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Aliya Lakhani, Da Hyun Kang, Yea Eun Kang, Junyoung O. Park
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Prevalence and Characteristics of Adrenal Tumors in an Unselected Screening Population
Ying Jing, Jinbo Hu, Rong Luo, Yun Mao, Zhixiao Luo, Mingjun Zhang, Jun Yang, Ying Song, Zhengping Feng, Zhihong Wang, Qingfeng Cheng, Linqiang Ma, Yi Yang, Li Zhong, Zhipeng Du, Yue Wang, Ting Luo, Wenwen He, Yue Sun, Fajin Lv, Qifu Li, Shumin Yang
Annals of Internal Medicine.2022; 175(10): 1383. CrossRef

Response

Adrenal Gland
Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age (Endocrinol Metab 2021;36:401-12, Seung Hun Lee et al.): Seung Hun Lee, Jong Woo Kim, Hyun-Ki Yoon, Jung-Min Koh, Chan Soo Shin, Sang Wan Kim, Jung Hee Kim; Endocrinol Metab. 2021;36(4):914-915. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.402

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Strategies for subtyping primary aldosteronism
Yun-Hsuan Yang, Yu-Ling Chang, Bo-Ching Lee, Ching-Chu Lu, Wei-Ting Wang, Ya-Hui Hu, Han-Wen Liu, Yung-Hsiang Lin, Chin-Chen Chang, Wan-Chen Wu, Fen-Yu Tseng, Yen-Hung Lin, Vin-Cent Wu, Chii-Min Hwu
Journal of the Formosan Medical Association.2024; 123: S114. CrossRef
Diagnostic consistency between computed tomography and adrenal vein sampling of primary aldosteronism: Leading to successful curative outcome after adrenalectomy: A retrospective study
Byung-Chang Kim, Hyun-Ki Yoon, Kye Jin Park, Gun Ha Kim, Shin Jeong Pak, Douk Kwon, Jae Won Cho, Won Woong Kim, Yu-mi Lee, Jung-Min Koh, Seung Hun Lee, Ki-Wook Chung, Tae-Yon Sung
International Journal of Surgery.2023;[Epub] CrossRef

Original Articles

Adrenal Gland
Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism: Ye Seul Yang, Seung Hun Lee, Jung Hee Kim, Jee Hee Yoo, Jung Hyun Lee, Seo Young Lee, A Ram Hong, Dong-Hwa Lee, Jung-Min Koh, Jae Hyeon Kim, Sang Wan Kim; Endocrinol Metab. 2021;36(4):875-884. Published online August 11, 2021; DOI: https://doi.org/10.3803/EnM.2021.1047

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Background
Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisol_nondominantperipheral) at AVS remains unclear. We aimed to investigate the clinical significance of CS and its impact on postoperative outcomes after unilateral adrenalectomy.
Methods
In this retrospective observational multi-center study, we analyzed PA patients who underwent both successful adrenocorticotropin hormone-stimulated AVS and unilateral adrenalectomy. Successful cannulation was defined as the selectivity index (cortisol_adrenal/ cortisol_peripheral) ≥3. Clinical and biochemical outcomes after unilateral adrenalectomy were evaluated based on the international Primary Aldosteronism Surgical Outcome consensus.
Results
Among 263 patients analyzed, 247 had CS (93.9%). Patients with CS had lower serum potassium levels, higher plasma aldosterone concentration, higher aldosterone-to-renin ratio (ARR), and larger adenoma size than those without CS. Those with CS showed significantly higher lateralization index than those without CS (P<0.001). Although postoperative blood pressure and ARR significantly decreased in those with CS, clinical and biochemical outcomes were comparable in both groups. When the cut-off value of age was determined using receiver operating characteristic (ROC) analysis, patients aged ≥50 years old with contralateral suppression index (CSI; the ratio between aldosterone/cortisol_nondominant and aldosterone/cortisol_peripheral) ≤0.26 had greater odds ratio (6.43; 95% confidence interval, 1.30 to 31.69) of incident chronic kidney disease than those aged <50 years with CSI >0.26 after adjusting for other factors.
Conclusion
CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

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Treatment decision based on unilateral index from nonadrenocorticotropic hormone-stimulated and adrenocorticotropic hormone-stimulated adrenal vein sampling in primary aldosteronism
Xizi Zhang, Xiaoyu Shu, Feifei Wu, Jun Yang, Qingfeng Cheng, Zhipeng Du, Ying Song, Yi Yang, Jinbo Hu, Yue Wang, Qifu Li, Shumin Yang
Journal of Hypertension.2024; 42(3): 450. CrossRef
Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes
Chang Ho Ahn, You-Bin Lee, Jae Hyeon Kim, Young Lyun Oh, Jung Hee Kim, Kyeong Cheon Jung
The Journal of Clinical Endocrinology & Metabolism.2024; 109(8): e1582. CrossRef
Development of a multivariate model predictive of post-adrenalectomy renal function decline in patients with primary aldosteronism: a large-cohort single-center study
Wenhao Lin, Juping Zhao, Chen Fang, Wei He, Xin Huang, Fukang Sun, Jun Dai
World Journal of Urology.2024;[Epub] CrossRef
Prognostic value of contralateral suppression on kidney function after surgery in patients with primary aldosteronism
Nathalie Voss, Sara Mørup, Caroline Clausen, Claus larsen Feltoft, Jan Viberg Jepsen, Mads Hornum, Mikkel Andreassen, Jesper Krogh
Clinical Endocrinology.2023; 98(3): 306. CrossRef
Factors Predicting Long-term Estimated Glomerular Filtration Rate Decrease, a Reliable Indicator of Renal Function After Adrenalectomy in Primary Aldosteronism
Qiyu He, Zhimin Tan, Yu Liu, Liang Zhou
Endocrine Practice.2023; 29(3): 199. CrossRef
Prognostic value of contralateral suppression for remission after surgery in patients with primary aldosteronism
Sara Mørup, Nathalie Voss, Caroline Clausen, Claus Larsen Feltoft, Mikkel Andreassen, Jesper Krogh
Clinical Endocrinology.2022; 96(6): 793. CrossRef
Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism (Endocrinol Metab 2021;36:875-84, Ye Seul Yang et al.)
Zhimin Tan, Qiyu He, Liang Zhou
Endocrinology and Metabolism.2022; 37(6): 951. CrossRef
Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism (Endocrinol Metab 2021;36:875-84, Ye Seul Yang et al.)
Ye Seul Yang, Sang Wan Kim
Endocrinology and Metabolism.2022; 37(6): 953. CrossRef

Clinical Study
Radioactive Parathyroid Adenomas on Sestamibi Scans: Low Parathyroid Hormone Secretory Potential and Large Volume: Sung Hye Kong, Jung Hee Kim, Sang Wan Kim, Chan Soo Shin; Endocrinol Metab. 2021;36(2):351-358. Published online April 6, 2021; DOI: https://doi.org/10.3803/EnM.2020.823

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Background
We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients.
Methods
The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent ^99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid.
Results
Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [–] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m². Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (–) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (–) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm³ [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm³ [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume.
Conclusion
Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.

Citations

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Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality
Sung Hye Kong, Jeong Mo Bae, Jung Hee Kim, Sang Wan Kim, Dohyun Han, Chan Soo Shin
Endocrinology and Metabolism.2024; 39(2): 375. CrossRef
Incidentally detected follicular thyroid carcinoma mimicking parathyroid adenoma on Tc-99m MIBI scan: A case report
Yeon-Hee Han, Hwan-Jeong Jeong, Sun Young Lee, Seok Tae Lim
Medicine.2024; 103(18): e38107. CrossRef
Atypical parathyroid tumor: clinical and parathyroid hormone response to surgical treatment
Antonio Giulio Napolitano, Massimo Monacelli, Valeria Liparulo, Eleonora Coviello, Domenico Pourmolkara, Stefano Avenia, Andrea Polistena
Annals of Surgical Treatment and Research.2023; 105(2): 76. CrossRef
The Relationship between Planar and SPECT/CT Parameters and Functional Markers in Primary Hyperparathyroidism
Guler Silov, Serpil Erdogan Ozbodur
Diagnostics.2023; 13(20): 3182. CrossRef

Clinical Study
Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age: Seung Hun Lee, Jong Woo Kim, Hyun-Ki Yoon, Jung-Min Koh, Chan Soo Shin, Sang Wan Kim, Jung Hee Kim; Endocrinol Metab. 2021;36(2):401-412. Published online March 31, 2021; DOI: https://doi.org/10.3803/EnM.2020.901

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Background
Guidelines by the Endocrine Society Guideline on bypassing adrenal vein sampling (AVS) in patients <35 years old with marked primary aldosteronism (PA) (hypokalemia and elevated plasma aldosterone concentration [PAC]) and a unilateral lesion on computed tomography (CT) are based on limited number of studies. We aimed to determine the accuracy of CT in PA patients according to age.
Methods
In this retrospective study, we investigated the concordance between CT and AVS in 466 PA patients from two tertiary centers who successfully underwent AVS.
Results
CT had an overall accuracy of 64.4% (300/466). In the group with unilateral lesion, patients with hypokalemia had higher concordance than those without hypokalemia (85.0% vs. 43.6%, P<0.001). In the group with marked PA (hypokalemia and PAC >15.9 ng/dL) and unilateral lesion, accuracy of CT was 84.6% (11/13) in patients aged <35 years; 100.0% (20/20), aged 35 to 39 years; 89.4% (59/66), aged 40 to 49 years; and 79.8% (79/99), aged ≥50 years. Cut-off age and PAC for concordance was <50 years and >29.6 ng/dL, respectively. The significant difference in accuracy of CT in 198 patients with marked PA and a unilateral lesion between the <50-year age group and ≥50-year age group (90.9% vs. 79.8%, P=0.044) disappeared in 139 of 198 patients with PAC > 30.0 ng/dL (91.9% vs. 87.7%, P=0.590).
Conclusion
Patients with hypokalemia, PAC >30.0 ng/dL, and unilateral lesion were at high risk of unilateral PA regardless of age.

Citations

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Adrenal Vein Sampling for Primary Aldosteronism: Recommendations From the Australian and New Zealand Working Group
Jun Yang, Damon A. Bell, Richard Carroll, Cherie Chiang, Diane Cowley, Emma Croker, James C. G. Doery, Marianne Elston, Paul Glendenning, Julie Hetherington, Andrea R. Horvath, Shanshan Lu‐Shirzad, Elisabeth Ng, Amanda Mather, Nimalie Perera, Muddassir Ra
Clinical Endocrinology.2025; 102(1): 31. CrossRef
Predicting Bilateral Subtypes of Primary Aldosteronism Without Adrenal Vein Sampling: A Systematic Review and Meta-analysis
Elisabeth Ng, Stella May Gwini, Winston Zheng, Peter J Fuller, Jun Yang
The Journal of Clinical Endocrinology & Metabolism.2024; 109(2): e837. CrossRef
Subtype-specific Body Composition and Metabolic Risk in Patients With Primary Aldosteronism
Seung Shin Park, Chang Ho Ahn, Sang Wan Kim, Ji Won Yoon, Jung Hee Kim
The Journal of Clinical Endocrinology & Metabolism.2024; 109(2): e788. CrossRef
Imaging Concordance With Vein Sampling for Primary Aldosteronism: A Cohort Study and Literature Review
Sara Cartwright, MaKayla Gordon, Jessica Shank, Abbey Fingeret
Journal of Surgical Research.2024; 296: 1. CrossRef
Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes
Chang Ho Ahn, You-Bin Lee, Jae Hyeon Kim, Young Lyun Oh, Jung Hee Kim, Kyeong Cheon Jung
The Journal of Clinical Endocrinology & Metabolism.2024; 109(8): e1582. CrossRef
Temporal trends in clinical features of patients with primary aldosteronism over 20 years
Seung Shin Park, Chang Ho Ahn, Sang Wan Kim, Jung-Min Koh, Seung Hun Lee, Jung Hee Kim
Hypertension Research.2024; 47(8): 2019. CrossRef
Best Practices: Indications and Procedural Controversies of Adrenal Vein Sampling for Primary Aldosteronism
Keith B. Quencer, Abhilasha Singh, Anu Sharma
American Journal of Roentgenology.2023; 220(2): 190. CrossRef
Accuracy of Gallium-68 Pentixafor Positron Emission Tomography–Computed Tomography for Subtyping Diagnosis of Primary Aldosteronism
Jinbo Hu, Tingting Xu, Hang Shen, Ying Song, Jun Yang, Aipin Zhang, Haoyuan Ding, Naiguo Xing, Zhuoyuan Li, Lin Qiu, Linqiang Ma, Yi Yang, Zhengping Feng, Zhipeng Du, Wenwen He, Yue Sun, Jun Cai, Qifu Li, Yue Chen, Shumin Yang, Mei Mei, Suxin Luo, Kangla
JAMA Network Open.2023; 6(2): e2255609. CrossRef
Adrenal Vein Sampling in the Young – Necessary or Not?
Eleftheria Gkaniatsa, Oskar Ragnarsson
Experimental and Clinical Endocrinology & Diabetes.2023; 131(07/08): 435. CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
Endocrinology and Metabolism.2023; 38(6): 597. CrossRef
Indices of ACTH‐stimulated adrenal venous sampling as predictors of postsurgical outcomes in primary aldosteronism
Seung Hun Lee, Jong Woo Kim, Hyun‐Ki Yoon, Sang Wan Kim, Su Jin Kim, Kyu Eun Lee, Yu‐Mi Lee, Tae‐Yon Sung, Suck Joon Hong, Chan Soo Shin, Jung‐Min Koh, Jung Hee Kim
Clinical Endocrinology.2022; 96(4): 521. CrossRef
Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism
Chang Ho Ahn, Hee Young Na, So Yeon Park, Hyeong Won Yu, Su‐Jin Kim, June Young Choi, Kyu Eun Lee, Sang Wan Kim, Kyeong Cheon Jung, Jung Hee Kim
Clinical Endocrinology.2022; 96(1): 30. CrossRef
Letter to the Editor From Singhania et al: “Increasing Incidence of Primary Aldosteronism in Western Sweden During 3 Decades—Yet an Underdiagnosed Disorder”
Pankaj Singhania, Rana Bhattacharjee
The Journal of Clinical Endocrinology & Metabolism.2022; 107(3): e1315. CrossRef
Development and validation of model for sparing adrenal venous sampling in diagnosing unilateral primary aldosteronism
Ying Song, Jun Yang, Hang Shen, Elisabeth Ng, Peter J. Fuller, Zhengping Feng, Jinbo Hu, Linqiang Ma, Yi Yang, Zhipeng Du, Yue Wang, Ting Luo, Wenwen He, Qifu Li, Fei-Fei Wu, Shumin Yang
Journal of Hypertension.2022; 40(9): 1692. CrossRef
Validation of Existing Clinical Prediction Tools for Primary Aldosteronism Subtyping
Barbora Kološová, Petr Waldauf, Dan Wichterle, Jan Kvasnička, Tomáš Zelinka, Ondřej Petrák, Zuzana Krátká, Lubomíra Forejtová, Jan Kaván, Jiří Widimský, Robert Holaj
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Fully automatic volume measurement of the adrenal gland on CT using deep learning to classify adrenal hyperplasia
Taek Min Kim, Seung Jae Choi, Ji Yeon Ko, Sungwan Kim, Chang Wook Jeong, Jeong Yeon Cho, Sang Youn Kim, Young-Gon Kim
European Radiology.2022; 33(6): 4292. CrossRef
Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age (Endocrinol Metab 2021;36:401-12, Seung Hun Lee et al.)
Seung Hun Lee, Jong Woo Kim, Hyun-Ki Yoon, Jung-Min Koh, Chan Soo Shin, Sang Wan Kim, Jung Hee Kim
Endocrinology and Metabolism.2021; 36(4): 914. CrossRef
Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age (Endocrinol Metab 2021;36:401-12, Seung Hun Lee et al.)
Pankaj Singhania
Endocrinology and Metabolism.2021; 36(4): 912. CrossRef

Brief Report

Hypothalamus and Pituitary gland
Reference Ranges of Serum Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3: Results from a Multicenter Study in Healthy Korean Adults: In-Kyung Jeong, Jong Kyu Byun, Junghyun Noh, Sang Wan Kim, Yoon-Sok Chung, Tae Sun Park, Sung-Woon Kim; Endocrinol Metab. 2020;35(4):954-959. Published online December 1, 2020; DOI: https://doi.org/10.3803/EnM.2020.785

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Insulin-like growth factor-I (IGF-I) plays a pivotal role in the diagnosis and treatment of growth hormone (GH) excess or deficiency. The GH study group of the Korean Endocrine Society aims to establish the Korean reference ranges of serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) and assess the relationship between IGF-I and IGFBP-3 and clinical parameters. Fasting serum was collected from healthy Korean adults at health promotion centers of five hospitals nationwide. Serum IGF-I and IGFBP-3 were measured via an immunoradiometric assay using a DSL kit (Diagnostic Systems Laboratories). Serum samples from 354 subjects (180 male, 174 female) were analyzed based on sex at 10-year intervals from 21 to 70 years. IGF-I levels were inversely correlated with age. After adjustment of age, the IGF-I/IGFBP-3 ratio was significantly negatively associated with blood pressure and free thyroxine and positively associated with weight, hemoglobin, creatinine, alanine transferase, fasting glucose, and thyroid stimulating hormone. Therefore, age- and sex-specific reference ranges of serum IGF-I and IGFBP-3 can be efficient in evaluating GH excess or deficiency in Korean population.

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Association of Uterine Leiomyoma with Type 2 Diabetes Mellitus in Young Women: A Population-Based Cohort Study
Ji-Hee Sung, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park
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Original Article

Clinical Study
Stimulated Salivary Cortisol as a Noninvasive Diagnostic Tool for Adrenal Insufficiency: Yoon Ji Kim, Jung Hee Kim, A Ram Hong, Kyeong Seon Park, Sang Wan Kim, Chan Soo Shin, Seong Yeon Kim; Endocrinol Metab. 2020;35(3):628-635. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.707

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Background
Salivary cortisol is routinely used as a diagnostic test for Cushing syndrome. The diagnostic use of salivary cortisol for adrenal insufficiency (AI), however, is less established. We aimed to investigate the utility of morning basal and adrenocorticotropic hormone-stimulated salivary cortisol in diagnosing AI in Korean adults.
Methods
We prospectively included 120 subjects (female, n=70) from Seoul National University Hospital. AI was defined as a stimulated serum cortisol level of <496.8 nmol/L during the short Synacthen test (SST). Serum and saliva samples were drawn between 8:00 AM and 10:00 AM. Salivary cortisol levels were measured using an enzyme immunoassay kit.
Results
Thirty-four patients were diagnosed with AI according to the SST results. Age, sex, body mass index, serum albumin levels, and serum creatinine levels did not significantly differ between the normal and AI groups. Basal and stimulated salivary cortisol levels were positively correlated with basal (r=0.538) and stimulated serum cortisol levels (r=0.750), respectively (all P<0.001). Receiver operating characteristic curve analysis yielded a cutoff level of morning basal salivary cortisol of 3.2 nmol/L (sensitivity, 84.9%; specificity, 73.5%; area under the curve [AUC]=0.822). The optimal cutoff value of stimulated salivary cortisol was 13.2 nmol/L (sensitivity, 90.7%; specificity, 94.1%; AUC=0.959). Subjects with a stimulated salivary cortisol level above 13.2 nmol/L but a stimulated serum cortisol level below 496.8 nmol/L (n=2) had lower serum albumin levels than those showing a concordant response.
Conclusion
The diagnostic performance of stimulated salivary cortisol measurements after the SST was comparable to serum cortisol measurements for diagnosing AI.

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