Endocrinology and Metabolism

Review Article

Miscellaneous
Brown Adipose Tissue: Activation and Metabolism in Humans: Imane Hachemi, Mueez U-Din; Endocrinol Metab. 2023;38(2):214-222. Published online March 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1659

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Brown adipose tissue (BAT) is a thermogenic organ contributing to non-shivering thermogenesis. BAT becomes active under cold stress via sympathetic nervous system activation. However, recent evidence has suggested that BAT may also be active at thermoneutrality and in a postprandial state. BAT has superior energy dissipation capacity compared to white adipose tissue (WAT) and muscles. Thus, it has been proposed that the recruitment and activation of additional BAT may increase the overall energy-expending capacity in humans, potentially improving current whole-body weight management strategies. Nutrition plays a central role in obesity and weight management. Thus, this review discusses human studies describing BAT hyper-metabolism after dietary interventions. Nutritional agents that can potentially recruit brown adipocytes via the process of BAT-WAT transdifferentiation are also discussed.

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Identification and functional analysis of a new cold induced LncRNA44154
Dongjie Zhang, Shouzheng Ma, Liang Wang, Di Liu
Gene.2025; 933: 148921. CrossRef
Spermidine activates adipose tissue thermogenesis through autophagy and fibroblast growth factor 21
Yinhua Ni, Liujie Zheng, Liqian Zhang, Jiamin Li, Yuxiang Pan, Haimei Du, Zhaorong Wang, Zhengwei Fu
The Journal of Nutritional Biochemistry.2024; 125: 109569. CrossRef
A natural sustained-intestinal release formulation of red chili pepper extracted capsaicinoids (Capsifen®) safely modulates energy balance and endurance performance: a randomized, double-blind, placebo-controlled study
N. Roopashree, Das S. Syam, I. M. Krishnakumar, K. N. Mala, Bradley S. Fleenor, Jestin Thomas
Frontiers in Nutrition.2024;[Epub] CrossRef
Thermogenic Fat as a New Obesity Management Tool: From Pharmaceutical Reagents to Cell Therapies
Ying Cheng, Shiqing Liang, Shuhan Zhang, Xiaoyan Hui
Biomedicines.2024; 12(7): 1474. CrossRef
Ling-gui-zhu-gan granules reduces obesity and ameliorates metabolic disorders by inducing white adipose tissue browning in obese mice
Yuxiu Li, Zimengwei Ye, Yi Zhao, Bingrui Xu, Wanying Xue, Zhufeng Wang, Ran An, Fan Wang, Rui Wu
Frontiers in Physiology.2024;[Epub] CrossRef
When Being Lean Is Not Enough: The Metabolically Unhealthy Normal Weight Phenotype and Cardiometabolic Disease
Dahyun Park, Min-Jeong Shin, Faidon Magkos
CardioMetabolic Syndrome Journal.2024; 4(2): 57. CrossRef
The Interplay between Liver and Adipose Tissue in the Onset of Liver Diseases: Exploring the Role of Vitamin Deficiency
Ivan Tattoli, Aimee Rachel Mathew, Antonella Verrienti, Lucia Pallotta, Carola Severi, Fausto Andreola, Virve Cavallucci, Mauro Giorgi, Mara Massimi, Lapo Bencini, Marco Fidaleo
Cells.2024; 13(19): 1631. CrossRef
Nutrition, hydration and supplementation considerations for mountaineers in high-altitude conditions: a narrative review
Ewa Karpęcka-Gałka, Barbara Frączek
Frontiers in Sports and Active Living.2024;[Epub] CrossRef
Whole-Body Cold Stimulation Improves Cardiac Autonomic Control Independently of the Employed Temperature
Nadia Solaro, Luca Giovanelli, Laura Bianchi, Paolo Piterà, Federica Verme, Mara Malacarne, Massimo Pagani, Jacopo Maria Fontana, Paolo Capodaglio, Daniela Lucini
Journal of Clinical Medicine.2024; 13(24): 7728. CrossRef
Brown Fat and Metabolic Health: The Diverse Functions of Dietary Components
Zachary Brown, Takeshi Yoneshiro
Endocrinology and Metabolism.2024; 39(6): 839. CrossRef
MRI Methods to Visualize and Quantify Adipose Tissue in Health and Disease
Katerina Nikiforaki, Kostas Marias
Biomedicines.2023; 11(12): 3179. CrossRef

Special Article

Adrenal gland
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, The Committee of Clinical Practice Guideline of Korean Endocrine Society, The Korean Adrenal Study Group of Korean Endocrine Society; Endocrinol Metab. 2023;38(6):597-618. Published online October 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1789

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Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.

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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
Primary aldosteronism: An underdiagnosed clinical entity
Peeyush Jain, Atul Kaushik, Nilashish Dey, Ashwani Mehta, Shaloo Kapoor, Chhavi Agrawal
Journal of Current Cardiology.2024; 2(2): 65. CrossRef
Historical changes in the clinical features of primary aldosteronism
Takamasa Ichijo
Hypertension Research.2024; 47(10): 2926. CrossRef
Comparing ARR Versus Suppressed PRA as Screening Tests for Primary Aldosteronism
Marco Marcelli, Caixia Bi, John W. Funder, Michael J. McPhaul
Hypertension.2024; 81(10): 2072. CrossRef
Screening and treatment of endocrine hypertension focusing on adrenal gland disorders: a narrative review
Seung Min Chung
Journal of Yeungnam Medical Science.2024; 41(4): 269. CrossRef
Differences in target organ damage between captopril challenge test-defined definitive-positive and borderline-range groups among patients with primary aldosteronism
Naoki Fujiwara, Tatsuya Haze, Hiromichi Wakui, Kouichi Tamura, Mika Tsuiki, Kohei Kamemura, Daisuke Taura, Takamasa Ichijo, Yutaka Takahashi, Minemori Watanabe, Hiroki Kobayashi, Toshifumi Nakamura, Shoichiro Izawa, Norio Wada, Tetsuya Yamada, Kenichi Yok
Hypertension Research.2024;[Epub] CrossRef
Diagnostic efficacy of aldosterone-to-renin ratio to screen primary aldosteronism in hypertension: a systemic review and meta-analysis
Ting-Wei Kao, Jui-Yi Chen, Jung-Hua Liu, Wen-Hsin Tseng, Chih-Chia Hsieh, Vin-Cent Wu, Yen-Hung Lin, Zheng-Wei Chen
Therapeutic Advances in Endocrinology and Metabolism.2024;[Epub] CrossRef
Comparative Analysis of Liquid Chromatography-Tandem Mass Spectrometry and Radioimmunoassay in Determining Plasma Aldosterone Concentration and Plasma Renin Activity for Primary Aldosteronism Screening
So Yoon Kwon, Kyeong-Jin Kim, Soo-Youn Lee, Jae Hyeon Kim
Endocrinology and Metabolism.2024; 39(6): 965. CrossRef

Review Articles

Adrenal gland
The Fascinating Interplay between Growth Hormone, Insulin-Like Growth Factor-1, and Insulin: Eline C. Nijenhuis-Noort, Kirsten A. Berk, Sebastian J. C. M. M. Neggers, Aart J. van der Lely; Endocrinol Metab. 2024;39(1):83-89. Published online January 9, 2024; DOI: https://doi.org/10.3803/EnM.2024.101

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This review intends to provide the reader with a practical overview of several (patho)physiological conditions in which knowledge of the interplay between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin is important. This might help treating physicians in making the right decisions on how to intervene and improve metabolism for the benefit of patients, and to understand why and how metabolism responds in their specific cases. We will specifically address the interplay between GH, IGF-1, and insulin in type 1 and 2 diabetes mellitus, liver cirrhosis, and acromegaly as examples in which this knowledge is truly necessary.

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Signaling pathways and targeted therapies in Ewing sarcoma
Ke Jia, Li Cao, Yihan Yu, Doudou Jing, Wei Wu, Brian Andrew Van Tine, Zengwu Shao
Pharmacology & Therapeutics.2025; 266: 108765. CrossRef
IGF-1 and IGF-2 as Molecules Linked to Causes and Consequences of Obesity from Fetal Life to Adulthood: A Systematic Review
Justyna Szydlowska-Gladysz, Adrianna Edyta Gorecka, Julia Stepien, Izabela Rysz, Iwona Ben-Skowronek
International Journal of Molecular Sciences.2024; 25(7): 3966. CrossRef
Insulin resistance reduction, intermittent fasting, and human growth hormone: secondary analysis of a randomized trial
Benjamin D. Horne, Jeffrey L. Anderson, Heidi T. May, Tami L. Bair, Viet T. Le, Leslie Iverson, Kirk U. Knowlton, Joseph B. Muhlestein
npj Metabolic Health and Disease.2024;[Epub] CrossRef
Insulin-Like Growth Factor Signaling in Alzheimer’s Disease: Pathophysiology and Therapeutic Strategies
Jie Miao, Yanli Zhang, Chen Su, Qiandan Zheng, Junhong Guo
Molecular Neurobiology.2024;[Epub] CrossRef
GHRH in diabetes and metabolism
Charlotte Steenblock, Stefan R. Bornstein
Reviews in Endocrine and Metabolic Disorders.2024;[Epub] CrossRef
Growth hormone/insulin-like growth factor I axis in health and disease states: an update on the role of intra-portal insulin
Kevin C. J. Yuen, Rikke Hjortebjerg, Ashok Ainkaran Ganeshalingam, David R. Clemmons, Jan Frystyk
Frontiers in Endocrinology.2024;[Epub] CrossRef
Expanding the Clinical and Mutational Spectrum of Biallelic POC1A Variants: Characterization of Four Patients and a Comprehensive Review of POC1A‐Related Phenotypes
Umut Altunoglu, Gozde Tutku Turgut, Esin Karakılıç Özturan, Tuğba Kalaycı, Mert Kaya, Güven Toksoy, Firdevs Baş, Hülya Kayserili, Feyza Darendeliler
Clinical Genetics.2024;[Epub] CrossRef

Adrenal Gland
Recent Updates on the Management of Adrenal Incidentalomas: Seung Shin Park, Jung Hee Kim; Endocrinol Metab. 2023;38(4):373-380. Published online August 16, 2023; DOI: https://doi.org/10.3803/EnM.2023.1779

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Adrenal incidentalomas represent an increasingly common clinical conundrum with significant implications for patients. The revised 2023 European Society of Endocrinology (ESE) guideline incorporates cutting-edge evidence for managing adrenal incidentalomas. This paper provides a concise review of the updated contents of the revised guideline. In the 2023 guideline, in patients without signs and symptoms of overt Cushing’s syndrome, a post-dexamethasone cortisol level above 50 nmol/L (>1.8 μg/dL) should be considered as mild autonomous cortisol secretion. Regarding the criteria of benign adrenal adenomas, a homogeneous adrenal mass with ≤10 Hounsfield units on non-contrast computed tomography requires no further follow-up, irrespective of its size. The updated guideline also discusses steroid metabolomics using tandem mass spectrometry to discriminate malignancy. It underscores the importance of high-volume surgeons performing adrenalectomy and emphasizes the pivotal role of a multidisciplinary team approach in deciding the treatment plan for indeterminate adrenal masses. The guideline advocates for more proactive surgical treatment for indeterminate adrenal masses in young patients (<40 years) and pregnant women. This review of the 2023 ESE guideline underscores the ongoing evolution of the adrenal incidentaloma management landscape, emphasizing the need for further research and adaptation of diagnostic and therapeutic strategies.

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Personalized Management of Malignant and Non-Malignant Ectopic Mediastinal Thyroid: A Proposed 10-Item Algorithm Approach
Mara Carsote, Mihai-Lucian Ciobica, Oana-Claudia Sima, Adrian Ciuche, Ovidiu Popa-Velea, Mihaela Stanciu, Florina Ligia Popa, Claudiu Nistor
Cancers.2024; 16(10): 1868. 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
Steroid Profiling in the Differential Diagnosis of Cushing's Syndrome and Diagnosis of MACS
A. Nankova, T. Kamenova, V. Vasilev, At. Elenkova, D. Svinarov, G. Kirilov, S. Zaharieva
Acta Medica Bulgarica.2024; 51(2): 1. CrossRef
Adrenal incidentalomas
Ivana Ságová
Vnitřní lékařství.2024; 70(5): E9. CrossRef
Ectopic Mediastinal Thyroid: A Crossroad Between a Multi-Layered Endocrine Perspective and a Contemporary Approach in Thoracic Surgery
Claudiu Nistor, Mihai-Lucian Ciobica, Oana-Claudia Sima, Anca-Pati Cucu, Florina Vasilescu, Lucian-George Eftimie, Dana Terzea, Mihai Costachescu, Adrian Ciuche, Mara Carsote
Life.2024; 14(11): 1374. CrossRef
Mature Adrenal Ganglioneuroma With Lipomatous Content: A Radiological and Histopathological Diagnostic Challenge
Mohammed Lameir Hussein, Shams O Alkhateeb, Jouhar J Kolleri, Ala' Saleem Abu-Dayeh, Khaled Murshed, Nabil Sherif Mahmood
Cureus.2024;[Epub] CrossRef
Comparative Analysis of Liquid Chromatography-Tandem Mass Spectrometry and Radioimmunoassay in Determining Plasma Aldosterone Concentration and Plasma Renin Activity for Primary Aldosteronism Screening
So Yoon Kwon, Kyeong-Jin Kim, Soo-Youn Lee, Jae Hyeon Kim
Endocrinology and Metabolism.2024; 39(6): 965. CrossRef

Original Article

Miscellaneous
Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review: Won Sang Yoo, Eu Jeong Ku, Eun Kyung Lee, Hwa Young Ahn; Endocrinol Metab. 2023;38(6):750-759. Published online November 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1785

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Background
This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs.
Methods
We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published.
Results
A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone.
Conclusion
Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.

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Management, biomarkers and prognosis in people developing endocrinopathies associated with immune checkpoint inhibitors
Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima
Nature Reviews Endocrinology.2025;[Epub] CrossRef
Start codon variant in LAG3 is associated with decreased LAG-3 expression and increased risk of autoimmune thyroid disease
Saedis Saevarsdottir, Kristbjörg Bjarnadottir, Thorsteinn Markusson, Jonas Berglund, Thorunn A. Olafsdottir, Gisli H. Halldorsson, Gudrun Rutsdottir, Kristbjorg Gunnarsdottir, Asgeir Orn Arnthorsson, Sigrun H. Lund, Lilja Stefansdottir, Julius Gudmundsson
Nature Communications.2024;[Epub] CrossRef
Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study
Tomoko Kobayashi, Shintaro Iwama, Ayana Yamagami, Tetsushi Izuchi, Koji Suzuki, Koki Otake, Yoshinori Yasuda, Masahiko Ando, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Naoki Nishio, Shoi
Cancer Immunology, Immunotherapy.2024;[Epub] CrossRef
Pituitary Complications of Checkpoint Inhibitor Use
Natalia Chamorro-Pareja, Alexander T Faje, Karen K Miller
Endocrinology.2024;[Epub] CrossRef
Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics
Ziyang Ye, Genpeng Li, Jianyong Lei
Experimental & Molecular Medicine.2024; 56(11): 2365. CrossRef
Neoadjuvant immunotherapy plus chemotherapy in high altitude natives with resectable esophageal squamous cell carcinoma in Tibet
Xizhao Sui, Duoji Danzeng, Ping Ni, Jiayi Geng, Pingcuo Gesang, Renqing Zhaxi, Yuling Wei
Asian Journal of Surgery.2024;[Epub] CrossRef

Review Articles

Adrenal gland
A Contemporary Approach to the Diagnosis and Management of Adrenal Insufficiency: Suranut Charoensri, Richard J. Auchus; Endocrinol Metab. 2024;39(1):73-82. Published online January 22, 2024; DOI: https://doi.org/10.3803/EnM.2024.1894

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Adrenal insufficiency (AI) can be classified into three distinct categories based on its underlying causes: primary adrenal disorders, secondary deficiencies in adrenocorticotropin, or hypothalamic suppression from external factors, most commonly glucocorticoid medications used for anti-inflammatory therapy. The hallmark clinical features of AI include fatigue, appetite loss, unintentional weight loss, low blood pressure, and hyponatremia. Individuals with primary AI additionally manifest skin hyperpigmentation, hyperkalemia, and salt craving. The diagnosis of AI is frequently delayed due to the non-specific symptoms and signs early in the disease course, which poses a significant challenge to its early detection prior to an adrenal crisis. Despite the widespread availability of lifesaving glucocorticoid medications for decades, notable challenges persist, particularly in the domains of timely diagnosis while simultaneously avoiding misdiagnosis, patient education for averting adrenal crises, and the determination of optimal replacement therapies. This article reviews recent advancements in the contemporary diagnostic strategy and approaches to optimal treatment for AI.

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Adrenal insufficiency in severely wounded men with combat gunshot injury
N.Yu. Seliukova, K.V. Misiura, E.M. Khoroshun, V.V. Makarov, V.V. Nehoduiko, O.I. Zalyubovska, E. Szucsik
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2025; 20(8): 573. CrossRef
Post-Traumatic Hypopituitarism
Nissa Blocher
Current Physical Medicine and Rehabilitation Reports.2024; 12(4): 405. CrossRef
Severe Fatigue in Uncontrolled Asthma: Contributing Factors and Impact of Rehabilitation
Karin B. Fieten, Lianne ten Have, Linde N. Nijhof, Lucia Rijssenbeek-Nouwens, Anneke ten Brinke
The Journal of Allergy and Clinical Immunology: In Practice.2024; 12(12): 3292. CrossRef
Adrenal Insufficiency in Patients with Beta Thalassemia: A Meta-Analysis
Christos Savvidis, Dimitra Ragia, Sophia Delicou, Aikaterini Xydaki, Manfredi Rizzo, Ioannis Ilias
Medicina.2024; 60(10): 1571. CrossRef
長期間の呼吸管理および遷延する低血圧から診断に至ったACTH単独欠損症の1例(A case of isolated ACTH deficiency diagnosed after long–term respiratory management and persistent hypotension)
古谷慎太郎, 神山治郎, 多喜亘, 山本大輔, 五木田昌士, 田口茂正, 清田和也
Nihon Kyukyu Igakukai Zasshi: Journal of Japanese Association for Acute Medicine.2024; 35(12): 965. CrossRef

Hypothalamus and pituitary gland
Update on Current Evidence for the Diagnosis and Management of Nonfunctioning Pituitary Neuroendocrine Tumors: Elizabeth Whyte, Masahiro Nezu, Constance Chik, Toru Tateno; Endocrinol Metab. 2023;38(6):631-654. Published online November 15, 2023; DOI: https://doi.org/10.3803/EnM.2023.1838

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Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all pituitary tumors and representing the most common type of macroPitNETs. NfPitNETs are usually benign tumors with no evidence of hormone oversecretion except for hyperprolactinemia secondary to pituitary stalk compression. Due to this, they do not typically present with clinical syndromes like acromegaly, Cushing’s disease or hyperthyroidism and instead are identified incidentally on imaging or from symptoms of mass effects (headache, vision changes, apoplexy). With the lack of effective medical interventions, first-line treatment is transsphenoidal surgical resection, however, nfPitNETs often have supra- or parasellar extension, and total resection of the tumor is often not possible, resulting in residual tumor regrowth or reoccurrence. While functional PitNETs can be easily followed for recurrence using hormonal biomarkers, there is no similar parameter to predict recurrence in nfPitNETs, hence delaying early recognition and timely management. Therefore, there is a need to identify prognostic biomarkers that can be used for patient surveillance and as therapeutic targets. This review focuses on summarizing the current evidence on nfPitNETs, with a special focus on potential new biomarkers and therapeutics.

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Phenotype Transformation of PitNETs
Zhenwei Li, Yinzi Wu, Guannan He, Renzhi Wang, Xinjie Bao
Cancers.2024; 16(9): 1731. CrossRef
Donor–Acceptor–Donor Strategy Rouses the Photodynamic Therapy Anticancer Activity of a Bis-terpyridyl Ru(II) Complex
Zhongyu Wang, Li Wei, Junfeng Lin, Can Huang, Huitong Chen, Dong Fan, Weiyu Hu, Jing Liu, Huaiyi Huang, Zongming Wang, Xin Wang
Journal of Medicinal Chemistry.2024; 67(15): 13435. CrossRef
A Study in Pituitary Neuroendocrine Tumors (PitNETs): Real-Life Data Amid Baseline and Serial CT Scans
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Cancers.2024; 16(20): 3477. CrossRef
Editorial: Prognostic factors in pituitary tumors: clinical, biochemical, imaging, and pathological aspects
Toru Tateno, Roxana-Ioana Dumitriu Stan, Stephanie Du Four
Frontiers in Endocrinology.2024;[Epub] CrossRef
Adaptive evaluation of gross total resection rates for endoscopic endonasal approach based on preoperative MRI morphological features of pituitary adenomas
Ao Shen, Yue Min, Dongjie Zhou, Lirui Dai, Liang Lyu, Wenyi Zhan, Shu Jiang, Peizhi Zhou
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Original Articles

Miscellaneous
Lipid Variability Induces Endothelial Dysfunction by Increasing Inflammation and Oxidative Stress: Marie Rhee, Joonyub Lee, Eun Young Lee, Kun-Ho Yoon, Seung-Hwan Lee; Endocrinol Metab. 2024;39(3):511-520. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2023.1915

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Background
This study investigates the impact of fluctuating lipid levels on endothelial dysfunction.
Methods
Human aortic and umbilical vein endothelial cells were cultured under varying palmitic acid (PA) concentrations: 0, 50, and 100 μM, and in a variability group alternating between 0 and 100 μM PA every 8 hours for 48 hours. In the lipid variability group, cells were exposed to 100 μM PA during the final 8 hours before analysis. We assessed inflammation using real-time polymerase chain reaction, Western blot, and cytokine enzyme-linked immunosorbent assay (ELISA); reactive oxygen species (ROS) levels with dichlorofluorescin diacetate assay; mitochondrial function through oxygen consumption rates via XF24 flux analyzer; and endothelial cell functionality via wound healing and cell adhesion assays. Cell viability was evaluated using the MTT assay.
Results
Variable PA levels significantly upregulated inflammatory genes and adhesion molecules (Il6, Mcp1, Icam, Vcam, E-selectin, iNos) at both transcriptomic and protein levels in human endothelial cells. Oscillating lipid levels reduced basal respiration, adenosine triphosphate synthesis, and maximal respiration, indicating mitochondrial dysfunction. This lipid variability also elevated ROS levels, contributing to a chronic inflammatory state. Functionally, these changes impaired cell migration and increased monocyte adhesion, and induced endothelial apoptosis, evidenced by reduced cell viability, increased BAX, and decreased BCL2 expression.
Conclusion
Lipid variability induce endothelial dysfunction by elevating inflammation and oxidative stress, providing mechanistic insights into how lipid variability increases cardiovascular risk.

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Association between triglyceride glucose index-related indices and kidney stones in adults based on NHANES 2007–2020
Ming Liu, Ping Yang, Yunpeng Gou
Frontiers in Endocrinology.2025;[Epub] CrossRef
Can Daily Dietary Choices Have a Cardioprotective Effect? Food Compounds in the Prevention and Treatment of Cardiometabolic Diseases
Elżbieta Szczepańska, Barbara Janota, Marika Wlazło, Magdalena Gacal
Metabolites.2024; 14(6): 296. CrossRef
Lipid Swings Provoke Vascular Inflammation
Jae-Han Jeon
Endocrinology and Metabolism.2024; 39(3): 448. CrossRef
Relationship between Oral Lichen Planus and Cardiovascular Disease of Atherosclerotic Origin: Systematic Review and Meta-Analysis
Beatriz Gonzalez Navarro, Sonia Egido Moreno, Carlos Omaña Cepeda, Albert Estrugo Devesa, Enric Jane Salas, Jose Lopez Lopez
Journal of Clinical Medicine.2024; 13(16): 4630. CrossRef

Adrenal gland Big Data Articles (National Health Insurance Service Database)
Mortality and Severity of Coronavirus Disease 2019 in Patients with Long-Term Glucocorticoid Therapy: A Korean Nationwide Cohort Study: Eu Jeong Ku, Keeho Song, Kyoung Min Kim, Gi Hyeon Seo, Soon Jib Yoo; Endocrinol Metab. 2023;38(2):253-259. Published online March 21, 2023; DOI: https://doi.org/10.3803/EnM.2022.1607

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Background
The severity of coronavirus disease 2019 (COVID-19) among patients with long-term glucocorticoid treatment (LTGT) has not been established. We aimed to evaluate the association between LTGT and COVID-19 prognosis.
Methods
A Korean nationwide cohort database of COVID-19 patients between January 2019 and September 2021 was used. LTGT was defined as exposure to at least 150 mg of prednisolone (≥5 mg/day and ≥30 days) or equivalent glucocorticoids 180 days before COVID-19 infection. The outcome measurements were mortality, hospitalization, intensive care unit (ICU) admission, length of stay, and mechanical ventilation.
Results
Among confirmed patients with COVID-19, the LTGT group (n=12,794) was older and had a higher proportion of comorbidities than the control (n=359,013). The LTGT group showed higher in-hospital, 30-day, and 90-day mortality rates than the control (14.0% vs. 2.3%, 5.9% vs. 1.1%, and 9.9% vs. 1.8%, respectively; all P<0.001). Except for the hospitalization rate, the length of stay, ICU admission, and mechanical ventilation proportions were significantly higher in the LTGT group than in the control (all P<0.001). Overall mortality was higher in the LTGT group than in the control group, and the significance remained in the fully adjusted model (odds ratio [OR], 5.75; 95% confidence interval [CI], 5.31 to 6.23) (adjusted OR, 1.82; 95% CI, 1.67 to 2.00). The LTGT group showed a higher mortality rate than the control within the same comorbidity score category.
Conclusion
Long-term exposure to glucocorticoids increased the mortality and severity of COVID-19. Prevention and early proactive measures are inevitable in the high-risk LTGT group with many comorbidities.

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Outpatient glucocorticoid use and COVID-19 outcomes: a population-based study
Almudena Rodríguez-Fernández, Irene Visos-Varela, Maruxa Zapata-Cachafeiro, Samuel Pintos-Rodríguez, Rosa M. García-Álvarez, Teresa M. Herdeiro, María Piñeiro-Lamas, Adolfo Figueiras, Ángel Salgado-Barreira, Rosendo Bugarín-González, Eduardo Carracedo-Mar
Inflammopharmacology.2024; 32(4): 2305. CrossRef
Glucocorticoids as a Double-Edged Sword in the Treatment of COVID-19: Mortality and Severity of COVID-19 in Patients Receiving Long-Term Glucocorticoid Therapy
Eun-Hee Cho
Endocrinology and Metabolism.2023; 38(2): 223. CrossRef
Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study
Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
Journal of Clinical Medicine.2023; 12(14): 4799. CrossRef

Review Article

Miscellaneous
Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer: Aliya Lakhani, Da Hyun Kang, Yea Eun Kang, Junyoung O. Park; Endocrinol Metab. 2023;38(6):619-630. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1814

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Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushing’s syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushing’s syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.

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Editorial: Tumor metabolism and programmed cell death
Dan-Lan Pu, Qi-Nan Wu
Frontiers in Endocrinology.2024;[Epub] CrossRef
Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies
Han Wang, Yang Liu, Aifa Tang, Xiansheng Zhang
European Journal of Medical Research.2024;[Epub] CrossRef

Original Article

Miscellaneous
AM1638, a GPR40-Full Agonist, Inhibited Palmitate- Induced ROS Production and Endoplasmic Reticulum Stress, Enhancing HUVEC Viability in an NRF2-Dependent Manner: Hwan-Jin Hwang, Joo Won Kim, SukHwan Yun, Min Jeong Park, Eyun Song, Sooyeon Jang, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo; Endocrinol Metab. 2023;38(6):760-769. Published online November 2, 2023; DOI: https://doi.org/10.3803/EnM.2023.1774

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Background
G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress.
Methods
Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium.
Results
In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2–related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. We also found that palmitate-induced CCAAT/enhancer‐binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner.
Conclusion
GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis.

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From oxidative stress to metabolic dysfunction: The role of TRPM2
Ying-Shuang Li, Hua-Cheng Ren, Hui Li, Man Xing, Jian-Hua Cao
International Journal of Biological Macromolecules.2025; 284: 138081. CrossRef
Free Fatty Acids and Free Fatty Acid Receptors: Role in Regulating Arterial Function
Fengzhi Yu, Boyi Zong, Lili Ji, Peng Sun, Dandan Jia, Ru Wang
International Journal of Molecular Sciences.2024; 25(14): 7853. CrossRef

Songwon Lecture 2022

Hypothalamus and pituitary gland
Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine: Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2023;38(5):463-471. Published online October 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1820

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The clinical characteristics and prognoses of acromegaly vary among patients. Assessment of current and novel predictors can lead to multilevel categorization of patients, allowing integration into new clinical guidelines and a reduction in the increased morbidity and mortality associated with acromegaly. Despite advances in the diagnosis and treatment of acromegaly, its pathophysiology remains unclear. Recent advancements in multiomics technologies, including genomics, transcriptomics, proteomics, metabolomics, and radiomics, have offered new opportunities to unravel the complex pathophysiology of acromegaly. This review comprehensively explores the emerging role of multiomics approaches in elucidating the molecular landscape of acromegaly. We discuss the potential implications of multiomics data integration in the development of novel diagnostic tools, identification of therapeutic targets, and the prospects of precision medicine in acromegaly management. By integrating diverse omics datasets, these approaches can provide valuable insights into disease mechanisms, facilitate the identification of diagnostic biomarkers, and identify potential therapeutic targets for precision medicine in the management of acromegaly.

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“Micromegaly”: Acromegaly with apparently normal GH, an entity on its own?
Lucio Vilar, Luciana Ansaneli Naves, Manoel Ricardo Alves Martins, Antônio Ribeiro-Oliveira Jr
Best Practice & Research Clinical Endocrinology & Metabolism.2024; 38(3): 101878. CrossRef

Original Articles

Miscellaneous
Association between N-Terminal Prohormone Brain Natriuretic Peptide and Decreased Skeletal Muscle Mass in a Healthy Adult Population: A Cross-Sectional Study: Tae Kyung Yoo, Marie Yung-Chen Wu, Moon Soo Kim, Mi-Yeon Lee, Yong-Taek Lee, Kyung Jae Yoon, Chul-Hyun Park; Endocrinol Metab. 2023;38(2):269-276. Published online March 13, 2023; DOI: https://doi.org/10.3803/EnM.2022.1588

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Background
Although an inverse association between the N-terminal prohormone brain natriuretic peptide (NT-proBNP) and obesity exists, only few major studies have assessed the association between NT-proBNP levels and skeletal muscle mass in asymptomatic healthy adults. Therefore, this cross-sectional study was conducted.
Methods
We assessed participants who underwent health examinations at Kangbuk Samsung Hospital in South Korea from January 2012 to December 2019. Appendicular skeletal muscle mass was measured using a bioelectrical impedance analyzer, and the skeletal muscle mass index (SMI) was calculated. Participants were divided into the control, mildly low skeletal muscle mass (LMM) (−2 standard deviation [SD] < SMI ≤−1 [SD]), and severely LMM groups (SD ≤−2) based on their SMI. The association between elevated NT-proBNP level (≥125 pg/mL) and skeletal muscle mass was assessed using multivariable logistic regression analysis with adjustment for confounding factors.
Results
This study enrolled 15,013 participants (mean age, 37.52±9.52; men, 54.24%; control, n=12,827; mildly LMM, n=1,998; severely LMM, n=188). Prevalence of elevated NT-proBNP was higher in mildly and severely LMM groups than in the control group (control, 1.19%; mildly LMM, 1.4%; severely LMM, 4.26%; P=0.001). The adjusted odds ratio (OR) of elevated NT-proBNP was significantly higher in severely LMM (OR, 2.87; 95% confidence interval [CI], 1.3 to 6.37) than in control (OR, 1.00; reference) or mildly LMM groups (OR, 1.24; 95% CI, 0.81 to 1.89).
Conclusion
Our results showed that NT-proBNP elevation were more prevalent in participants with LMM. In addition, our study showed an association between skeletal muscle mass and NT-proBNP level in a relatively young and healthy adult population.

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Differences in the Evaluation of Malnutrition and Body Composition Using Bioelectrical Impedance Analysis, Nutritional Ultrasound, and Dual-Energy X-ray Absorptiometry in Patients with Heart Failure
Ana Benitez-Velasco, Carlos Alzas-Teomiro, Carmen Zurera Gómez, Concepción Muñoz Jiménez, José López Aguilera, Manuel Crespin, Juan Antonio Vallejo-Casas, María Ángeles Gálvez-Moreno, María José Molina Puerta, Aura D. Herrera-Martínez
Nutrients.2024; 16(10): 1535. CrossRef

Hypothalamus and pituitary gland
Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience: Jung Heo, Yeon-Lim Suh, Se Hoon Kim, Doo-Sik Kong, Do-Hyun Nam, Won-Jae Lee, Sung Tae Kim, Sang Duk Hong, Sujin Ryu, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim, Kyu Yeon Hur; Endocrinol Metab. 2024;39(2):387-396. Published online February 5, 2024; DOI: https://doi.org/10.3803/EnM.2023.1877

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Background
Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity.
Methods
A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared.
Results
Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered.
Conclusion
The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

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TSH-secreting pituitary adenomas and bone
Marco Losa, Alberto Vassallo, Stefano Frara, Pietro Mortini, Andrea Giustina
Pituitary.2024; 27(6): 752. CrossRef

Miscellaneous
Differences in Type 2 Fiber Composition in the Vastus Lateralis and Gluteus Maximus of Patients with Hip Fractures: Jingwen Tian, Minchul Song, Kyu Jeong Cho, Ho Yeop Lee, Sang Hyeon Ju, Jung Ryul Lim, Ha Thi Nga, Thi Linh Nguyen, Ji Sun Moon, Hyo Ju Jang, Jung-Mo Hwang, Hyon-Seung Yi; Endocrinol Metab. 2024;39(3):521-530. Published online June 11, 2024; DOI: https://doi.org/10.3803/EnM.2024.1935

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Background
Aging leads to sarcopenia, which is characterized by reduced muscle mass and strength. Many factors, including altered muscle protein turnover, diminished neuromuscular function, hormonal changes, systemic inflammation, and the structure and composition of muscle fibers, play a crucial role in age-related muscle decline. This study explored differences in muscle fiber types contributing to overall muscle function decline in aging, focusing on individuals with hip fractures from falls.
Methods
A pilot study at Chungnam National University Hospital collected muscle biopsies from hip fracture patients aged 20 to 80 undergoing surgical treatment. Muscle biopsies from the vastus lateralis and gluteus maximus were obtained during hip arthroplasty or internal fixation. Handgrip strength, calf and thigh circumference, and bone mineral density were evaluated in individuals with hip fractures from falls. We analyzed the relationships between each clinical characteristic and muscle fiber type.
Results
In total, 26 participants (mean age 67.9 years, 69.2% male) were included in this study. The prevalence of sarcopenia was 53.8%, and that of femoral and lumbar osteoporosis was 19.2% and 11.5%, respectively. Vastus lateralis analysis revealed an age-related decrease in type IIx fibers, a higher proportion of type IIa fibers in women, and an association between handgrip strength and type IIx fibers in men. The gluteus maximus showed no significant correlations with clinical parameters.
Conclusion
This study identified complex associations between age, sex, handgrip strength, and muscle fiber composition in hip fracture patients, offering insights crucial for targeted interventions combating age-related muscle decline and improving musculoskeletal health.

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Tourniquet Use During ACL Reconstruction Is Associated With Postoperative Quadriceps Atrophy and Pain but No Negative Effects in the Long Term: A Systematic Review
Caleb V. Hayes, Saad M. Ibrahim, Anna E. Crawford, James R. Jones, Mathew D. Hargreaves, Clay A. Rahaman, Eugene W. Brabston, Thomas B. Evely, Aaron J. Casp, Kevin E. Wilk, Amit M. Momaya
Arthroscopy, Sports Medicine, and Rehabilitation.2024; : 101040. CrossRef

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