Endocrinology and Metabolism

Original Articles

⁶⁸Ga-DOTATOC PET/CT in the Localization of Pituitary Tumors in Cushing’s Disease: Kyungwon Kim, Dongwoo Kim, Min-Ho Lee, Yae Won Park, Sung Soo Ahn, Ju Hyung Moon, Eui Hyun Kim, Sun Ho Kim, Cheol Ryong Ku, Eun Jig Lee; Received November 20, 2024 Accepted January 21, 2025 Published online March 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2249 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
This study aimed to determine the value of ⁶⁸Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) in localizing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas.
Methods
In this retrospective cohort study, we enrolled 30 patients with Cushing’s disease and positive ACTH immunoreactivity. All patients underwent ⁶⁸Ga-DOTATOC PET/CT and pituitary magnetic resonance imaging (MRI) before transsphenoidal adenomectomy.
Results
Twenty-five patients showed ⁶⁸Ga-DOTATOC uptake in their pituitary glands on PET/CT. Median age, pre-operative ACTH levels, pre-operative cortisol, and tumor size on MRI were comparable irrespective of DOTATOC uptake. ⁶⁸Ga-DOTATOC PET/CT showed a 77% success rate for localizing adenomas, which was not statistically different from that of MRI. The ACTH level in the successful localization group was significantly higher than that in the failed group (84.41 pg/mL vs. 37.26 pg/mL, P=0.001). The ACTH level was statistically significant predictor of successful localization using ⁶⁸Ga-DOTATOC PET/CT (P=0.013). The area under the curve was 0.932 with a cutoff of 53.86 pg/mL for ACTH levels to determine successful localization. Pre-operative ACTH levels above 53.86 pg/mL showed the best diagnostic accuracy in predicting the success of localizing adenomas (sensitivity, 91.3%; specificity, 85.7%). Mean and maximum standardized uptake value of adenoma negatively correlated to pre-operative ACTH level.
Conclusion
Plasma ACTH level is a favorable predictor for the successful localization and negative correlation with ⁶⁸Ga-DOTATOC uptake of corticotroph adenomas in ⁶⁸Ga-DOTATOC PET/CT. ⁶⁸Ga-DOTATOC PET/CT did not improve tumor localization for Cushing’s disease compared with MRI alone.

Mineral, Bone & Muscle
Carnitine Metabolite as a Potential Circulating Biomarker for Sarcopenia in Men: Je Hyun Seo, Jung-Min Koh, Han Jin Cho, Hanjun Kim, Young‑Sun Lee, Su Jung Kim, Pil Whan Yoon, Won Kim, Sung Jin Bae, Hong-Kyu Kim, Hyun Ju Yoo, Seung Hun Lee; Endocrinol Metab. 2025;40(1):93-102. Published online November 28, 2024; DOI: https://doi.org/10.3803/EnM.2024.2117

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Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia.
Methods
Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort.
Results
An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027).
Conclusion
C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Review Article

Hypothalamus and pituitary gland
Elucidating Clinical Queries for Tailored Therapy in Patients with Prolactinoma: Min-Ho Lee, Jae Won Hong, Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2024;39(6):819-826. Published online October 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.2057

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Prolactinomas are the most prevalent type of pituitary neuroendocrine adenomas, primarily affecting women of reproductive age. Unlike other pituitary tumors, the first-line management has traditionally been pharmacological rather than surgical. This preference is due to the effectiveness of dopamine agonists (DAs), which typically reduce tumor size and normalize prolactin levels in most patients. However, this does not imply that there is no room for improvement; the duration of treatment and medication side effects often lead to compliance issues among patients. Recent advances in surgical techniques and molecular biology have paved the way for the development of precision medicine, allowing for more flexible and personalized treatment strategies for prolactinomas. This review aims to enhance clinical decision-making and patient care for endocrinologists by focusing on several key factors: predictive markers of DA sensitivity, clinical characteristics and suitability for transsphenoidal adenomectomy as a potential first-line treatment, factors determining the successful withdrawal of DAs after prolonged use, safety concerns during pre/post-pregnancy and breastfeeding, and determinants of tumor aggressiveness. Through tailored therapy—a patient-focused, multidisciplinary approach— we aim to improve the management of prolactinoma patients.

Citations

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When to embark on surgery for prolactin-secreting pituitary adenoma?
Nazmin Ahmed, Subodh Gautam, Bipin Chaurasia
Annals of Medicine & Surgery.2025; 87(4): 1798. CrossRef

Original Articles

Diabetes, obesity and metabolism
FoxO6-Mediated TXNIP Induces Lipid Accumulation in the Liver through NLRP3 Inflammasome Activation: Mi Eun Kim, Jun Sik Lee, Tae Won Kim, Min Hi Park, Dae Hyun Kim; Endocrinol Metab. 2024;39(1):127-139. Published online February 22, 2024; DOI: https://doi.org/10.3803/EnM.2023.1826

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Background
Hepatic steatosis, which involves the excessive accumulation of lipid droplets in hepatocytes, presents a significant global health concern due to its association with obesity and metabolic disorders. Inflammation plays a crucial role in the progression of hepatic steatosis; however, the precise molecular mechanisms responsible for this process remain unknown.
Methods
This study investigated the involvement of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome and the forkhead box O6 (FoxO6) transcription factor in the pathogenesis of hepatic steatosis. We monitored the NLRP3 inflammasome and lipogenesis in mice overexpressing the constitutively active (CA)-FoxO6 allele and FoxO6-null mice. In an in vitro study, we administered palmitate to liver cells overexpressing CA-FoxO6 and measured changes in lipid metabolism.
Results
We administered palmitate treatment to clarify the mechanisms through which FoxO6 activates cytokine interleukin (IL)-1β through the NLRP3 inflammasome. The initial experiments revealed that dephosphorylation led to palmitate-induced FoxO6 transcriptional activity. Further palmitate experiments showed increased expression of IL-1β and the hepatic NLRP3 inflammasome complex, including adaptor protein apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Furthermore, thioredoxin-interacting protein (TXNIP), a key regulator of cellular redox conditions upstream of the NLRP3 inflammasome, was induced by FoxO6 in the liver and HepG2 cells.
Conclusion
The findings of this study shed light on the molecular mechanisms underpinning the FoxO6-NLRP3 inflammasome axis in promoting inflammation and lipid accumulation in the liver.

Citations

Citations to this article as recorded by

FOXO6: A unique transcription factor in disease regulation and therapeutic potential
Songzhe Li, Ting Ye, Zhitao Hou, Yuqing Wang, Zhihua Hao, Jing Chen
Pharmacological Research.2025; 214: 107691. CrossRef
Identifying differentially expressed genes in goat mammary epithelial cells induced by overexpression of SOCS3 gene using RNA sequencing
Ning Song, Cunxia Ma, Yuzhu Guo, Shuangshuang Cui, Shihao Chen, Zhi Chen, Yinghui Ling, Yunhai Zhang, Hongyu Liu
Frontiers in Veterinary Science.2024;[Epub] CrossRef

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.

Citations

Citations to this article as recorded by

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
Discovery of potent free fatty acid receptor 1 full agonists with a novel scaffold bearing conjugated double bond linker
Ziwei Yang, Jun Sun, Tifei Xu, Yu Wang, Jiahui Fang, Kai Wang, Shimeng Guo, Xin Xie, Jianhua Shen
Bioorganic & Medicinal Chemistry.2025; 123: 118158. CrossRef
GPR40-full agonist AM1638 alleviates palmitate-induced oxidative damage in H9c2 cells via an AMPK-dependent pathway
SukHwan Yun, Joo Won Kim, Min Jeong Park, Eyun Song, Soo Yeon Jang, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hwan-Jin Hwang, Hye Jin Yoo
BMB Reports.2025; 58(3): 133. CrossRef
HD6277 Suppresses Muscle Atrophy by Promoting Myogenic Factors and Inhibiting Proteolysis in Aged Mice
Joo Won Kim, SukHwan Yun, Min Jeong Park, Eyun Song, Sooyeon Jang, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hwan‐Jin Hwang, Hye Jin Yoo
Journal of Cachexia, Sarcopenia and Muscle.2025;[Epub] 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

Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
Increased Risk of Hip Fracture in Patients with Acromegaly: A Nationwide Cohort Study in Korea: Jiwon Kim, Namki Hong, Jimi Choi, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Sin Gon Kim, Cheol Ryong Ku; Endocrinol Metab. 2023;38(6):690-700. Published online October 30, 2023; DOI: https://doi.org/10.3803/EnM.2023.1782

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Background
Acromegaly leads to various skeletal complications, and fragility fractures are emerging as a new concern in patients with acromegaly. Therefore, this study investigated the risk of fractures in Korean patients with acromegaly.
Methods
We used the Korean nationwide claims database from 2009 to 2019. A total of 931 patients with acromegaly who had never used an osteoporosis drug before and were treated with surgery alone were selected as study participants, and a 1:29 ratio of 26,999 age- and sex-matched osteoporosis drug-naïve controls without acromegaly were randomly selected from the database.
Results
The mean age was 46.2 years, and 50.0% were male. During a median follow-up of 54.1 months, there was no difference in the risks of all, vertebral, and non-vertebral fractures between the acromegaly and control groups. However, hip fracture risk was significantly higher (hazard ratio [HR], 2.73; 95% confidence interval [CI], 1.32 to 5.65), and non-hip and non-vertebral fractures risk was significantly lower (HR, 0.40; 95% CI, 0.17 to 0.98) in patients with acromegaly than in controls; these results remained robust even after adjustment for socioeconomic status and baseline comorbidities. Age, type 2 diabetes mellitus, cardio-cerebrovascular disease, fracture history, recent use of acid-suppressant medication, psychotropic medication, and opioids were risk factors for all fractures in patients with acromegaly (all P<0.05).
Conclusion
Compared with controls, patients surgically treated for acromegaly had a higher risk of hip fractures. The risk factors for fracture in patients with acromegaly were consistent with widely accepted risk factors in the general population.

Citations

Citations to this article as recorded by

Long-Term Prognosis and Systemic Impact of Acromegaly: Analyses Utilizing Korean National Health Insurance Data
Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2025; 40(1): 1. CrossRef
Musculoskeletal disease in acromegaly—a population-based registry study
Christian Rosendal, Mai Christiansen Arlien-Søborg, Eigil Husted Nielsen, Claus Larsen Feltoft, Åse Krogh Rasmussen, Marianne Skovsager Andersen, Jens Otto Lunde Jørgensen, Jakob Dal
European Journal of Endocrinology.2025; 192(3): 308. CrossRef
Novel approach to bone comorbidity in resistant acromegaly
Stefano Frara, Matteo Acanfora, Vincenzo Franzese, Maria Luisa Brandi, Marco Losa, Andrea Giustina
Pituitary.2024; 27(6): 813. 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.

Citations

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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

Brief Report

Diabetes, Obesity and Metabolism
Sestrin2 Regulates Beneficial β3-Adrenergic Receptor-Mediated Effects Observed in Inguinal White Adipose Tissue and Soleus Muscle: Min Jeong Park, Joo Won Kim, Eun Roh, Kyung Mook Choi, Sei Hyun Baik, Hwan-Jin Hwang, Hye Jin Yoo; Endocrinol Metab. 2022;37(3):552-557. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1421

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Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The β3-adrenergic receptor (β3AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with β3AR in body composition changes. In this study, CL 316,243 (CL), a β3AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2-KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial β3AR-mediated changes in body composition, especially in iWAT and in the soleus.

Citations

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Sestrin2 levels in patients with anxiety and depression myocardial infarction was up-regulated and suppressed inflammation and ferroptosis by LKB1-mediated AMPK activation
Yufeng Qian, Lian Chen, Beibei Gao, Xianhua Ye
Clinical and Experimental Hypertension.2023;[Epub] CrossRef
Sestrin2 in diabetes and diabetic complications
Xiaodan Zhang, Zirui Luo, Jiahong Li, Yaxuan Lin, Yu Li, Wangen Li
Frontiers in Endocrinology.2023;[Epub] CrossRef

Original Articles

Diabetes, Obesity and Metabolism
Effect of the Concomitant Use of Subcutaneous Basal Insulin and Intravenous Insulin Infusion in the Treatment of Severe Hyperglycemic Patients: Yejee Lim, Jung Hun Ohn, Joo Jeong, Jiwon Ryu, Sun-wook Kim, Jae Ho Cho, Hee-Sun Park, Hye Won Kim, Jongchan Lee, Eun Sun Kim, Nak-Hyun Kim, You Hwan Jo, Hak Chul Jang; Endocrinol Metab. 2022;37(3):444-454. Published online June 3, 2022; DOI: https://doi.org/10.3803/EnM.2021.1341

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Background
No consensus exists regarding the early use of subcutaneous (SC) basal insulin facilitating the transition from continuous intravenous insulin infusion (CIII) to multiple SC insulin injections in patients with severe hyperglycemia other than diabetic ketoacidosis. This study evaluated the effect of early co-administration of SC basal insulin with CIII on glucose control in patients with severe hyperglycemia.
Methods
Patients who received CIII for the management of severe hyperglycemia were divided into two groups: the early basal insulin group (n=86) if they received the first SC basal insulin 0.25 U/kg body weight within 24 hours of CIII initiation and ≥4 hours before discontinuation, and the delayed basal insulin group (n=79) if they were not classified as the early basal insulin group. Rebound hyperglycemia was defined as blood glucose level of >250 mg/dL in 24 hours following CIII discontinuation. Propensity score matching (PSM) methods were additionally employed for adjusting the confounding factors (n=108).
Results
The rebound hyperglycemia incidence was significantly lower in the early basal insulin group than in the delayed basal insulin group (54.7% vs. 86.1%), despite using PSM methods (51.9%, 85.2%). The length of hospital stay was shorter in the early basal insulin group than in the delayed basal insulin group (8.5 days vs. 9.6 days, P=0.027). The hypoglycemia incidence did not differ between the groups.
Conclusion
Early co-administration of basal insulin with CIII prevents rebound hyperglycemia and shorten hospital stay without increasing the hypoglycemic events in patients with severe hyperglycemia.

Citations

Citations to this article as recorded by

16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2025
Nuha A. ElSayed, Rozalina G. McCoy, Grazia Aleppo, Kirthikaa Balapattabi, Elizabeth A. Beverly, Kathaleen Briggs Early, Dennis Bruemmer, Justin B. Echouffo-Tcheugui, Laya Ekhlaspour, Rodolfo J. Galindo, Rajesh Garg, Kamlesh Khunti, Rayhan Lal, Ildiko Ling
Diabetes Care.2025; 48(Supplement): S321. CrossRef
Evaluation of hyperglycaemic emergency admissions to a major tertiary centre over a two‐year period
Serena Chong, Hannah Rubinstein, Tang Wong, Ann Poynten
Diabetic Medicine.2025;[Epub] CrossRef
16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2024
Nuha A. ElSayed, Grazia Aleppo, Raveendhara R. Bannuru, Dennis Bruemmer, Billy S. Collins, Laya Ekhlaspour, Rodolfo J. Galindo, Marisa E. Hilliard, Eric L. Johnson, Kamlesh Khunti, Ildiko Lingvay, Glenn Matfin, Rozalina G. McCoy, Mary Lou Perry, Scott J.
Diabetes Care.2024; 47(Supplement): S295. CrossRef
Retrospective Comparison of Early Versus Late Initiation of Long-Acting Insulin in Critically Ill Pediatric Patients in Diabetic Ketoacidosis
Emily S. Cormack, Amber Howard, Derrick Eddy, Nick Schulte
The Journal of Pediatric Pharmacology and Therapeutics.2024; 29(6): 614. CrossRef
16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2023
Nuha A. ElSayed, Grazia Aleppo, Vanita R. Aroda, Raveendhara R. Bannuru, Florence M. Brown, Dennis Bruemmer, Billy S. Collins, Marisa E. Hilliard, Diana Isaacs, Eric L. Johnson, Scott Kahan, Kamlesh Khunti, Jose Leon, Sarah K. Lyons, Mary Lou Perry, Priya
Diabetes Care.2023; 46(Supplement): S267. CrossRef
Effectiveness and safety of early insulin glargine administration in combination with continuous intravenous insulin infusion in the management of diabetic ketoacidosis: A randomized controlled trial
Kitti Thammakosol, Chutintorn Sriphrapradang
Diabetes, Obesity and Metabolism.2023; 25(3): 815. CrossRef

Diabetes, Obesity and Metabolism
Non-Laboratory-Based Simple Screening Model for Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Developed Using Multi-Center Cohorts: Jiwon Kim, Minyoung Lee, Soo Yeon Kim, Ji-Hye Kim, Ji Sun Nam, Sung Wan Chun, Se Eun Park, Kwang Joon Kim, Yong-ho Lee, Joo Young Nam, Eun Seok Kang; Endocrinol Metab. 2021;36(4):823-834. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1074

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Background
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is a risk factor that accelerates NAFLD progression, leading to fibrosis and cirrhosis. Thus, here we aimed to develop a simple model to predict the presence of NAFLD based on clinical parameters of patients with T2DM.
Methods
A total of 698 patients with T2DM who visited five medical centers were included. NAFLD was evaluated using transient elastography. Univariate logistic regression analyses were performed to identify potential contributors to NAFLD, followed by multivariable logistic regression analyses to create the final prediction model for NAFLD.
Results
Two NAFLD prediction models were developed, with and without serum biomarker use. The non-laboratory model comprised six variables: age, sex, waist circumference, body mass index (BMI), dyslipidemia, and smoking status. For a cutoff value of ≥60, the prediction accuracy was 0.780 (95% confidence interval [CI], 0.743 to 0.817). The second comprehensive model showed an improved discrimination ability of up to 0.815 (95% CI, 0.782 to 0.847) and comprised seven variables: age, sex, waist circumference, BMI, glycated hemoglobin, triglyceride, and alanine aminotransferase to aspartate aminotransferase ratio. Our non-laboratory model showed non-inferiority in the prediction of NAFLD versus previously established models, including serum parameters.
Conclusion
The new models are simple and user-friendly screening methods that can identify individuals with T2DM who are at high-risk for NAFLD. Additional studies are warranted to validate these new models as useful predictive tools for NAFLD in clinical practice.

Citations

Citations to this article as recorded by

Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus—The Chicken or the Egg Dilemma
Marcin Kosmalski, Agnieszka Śliwińska, Józef Drzewoski
Biomedicines.2023; 11(4): 1097. CrossRef

Diabetes, Obesity and Metabolism
Reference Values for Skeletal Muscle Mass at the Third Lumbar Vertebral Level Measured by Computed Tomography in a Healthy Korean Population: Ja Kyung Yoon, Sunyoung Lee, Kyoung Won Kim, Ji Eun Lee, Jeong Ah Hwang, Taeyong Park, Jeongjin Lee; Endocrinol Metab. 2021;36(3):672-677. Published online June 8, 2021; DOI: https://doi.org/10.3803/EnM.2021.1041

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Background
Sarcopenia is defined as the loss of skeletal muscle mass and is associated with negative clinical outcomes. This study aimed to establish sex-specific cutoff values for the skeletal muscle area (SMA) and skeletal muscle index (SMI) at the third lumbar vertebral (L3) level using computed tomography (CT) imaging to identify sarcopenia in healthy Korean liver donors.
Methods
This retrospective study included 659 healthy liver donors (408 men and 251 women) aged 20 to 60 years who had undergone abdominal CT examinations between January 2017 and December 2018. Assessment of body composition was performed with an automated segmentation technique using a deep-learning system. Sex-specific SMA and SMI distributions were assessed, and cutoff values for determining sarcopenia were defined as values at either two standard deviations (SDs) below the mean reference value or below the fifth percentile.
Results
Using the SD definition, cutoff values for SMA and SMI were 117.04 cm² and 39.33 cm²/m², respectively, in men and 71.39 cm² and 27.77 cm²/m², respectively, in women. Using the fifth percentile definition, cutoff values for SMA and SMI were 126.88 cm² and 40.96 cm²/m², respectively, in men and 78.85 cm² and 30.60 cm²/m², respectively, in women.
Conclusion
Our data provide sex-specific cutoff values for the SMA and SMI at the L3 level measured by CT imaging in a healthy Korean population, which may be applicable for identifying sarcopenia in this population.

Citations

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Association of Sarcopenia With Toxicity and Survival in Patients With Lung Cancer, a Multi-Institutional Study With External Dataset Validation
Anurag Saraf, John He, Kee-Young Shin, Jakob Weiss, Mark M. Awad, Justin Gainor, Benjamin H. Kann, David C. Christiani, Hugo J.W.L. Aerts, Raymond H. Mak
Clinical Lung Cancer.2025;[Epub] CrossRef
Sarcopenia is independently associated with mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy
Il Young Kim, Byung Min Ye, Seo Rin Kim, Dong Won Lee, Soo Bong Lee
Kidney Research and Clinical Practice.2025; 44(2): 324. CrossRef
Myosteatosis is associated with poor survival after kidney transplantation: a large retrospective cohort validation
Jie Chen, Yue Li, Chengjie Li, Turun Song
Abdominal Radiology.2024; 49(4): 1210. CrossRef
Relative muscle indices and healthy reference values for sarcopenia assessment using T10 through L5 computed tomography skeletal muscle area
Brian A. Derstine, Sven A. Holcombe, Nicholas C. Wang, Brian E. Ross, June A. Sullivan, Stewart C. Wang, Grace L. Su
Scientific Reports.2024;[Epub] CrossRef
Prognostic Value of Sarcopenia in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer Undergoing Radiotherapy
Valerio Nardone, Alfonso Reginelli, Vittorio Patanè, Angelo Sangiovanni, Roberta Grassi, Anna Russo, Pierpaolo Correale, Diego Sandro Giordano, Carmine Zaccaria, Maria Paola Belfiore, Salvatore Cappabianca
Current Oncology.2024; 31(11): 6673. CrossRef
Preoperative low skeletal muscle mass index assessed using L3-CT as a prognostic marker of clinical outcomes in pancreatic cancer patients undergoing surgery: a systematic review and meta-analysis
Pauline Raoul, Marco Cintoni, Alessandro Coppola, Sergio Alfieri, Giampaolo Tortora, Antonio Gasbarrini, Maria Cristina Mele, Emanuele Rinninella
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Clinical Study
Associations of GNAS Mutations with Surgical Outcomes in Patients with Growth Hormone-Secreting Pituitary Adenoma: Hyein Jung, Kyungwon Kim, Daham Kim, Ju Hyung Moon, Eui Hyun Kim, Se Hoon Kim, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2021;36(2):342-350. Published online March 23, 2021; DOI: https://doi.org/10.3803/EnM.2020.875

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Background
The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics.
Methods
We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor.
Results
GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively).
Conclusion
GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

Citations

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Contract to kill: GNAS mutation
Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy
Molecular Cancer.2025;[Epub] CrossRef
Genetic diagnosis in acromegaly and gigantism: From research to clinical practice
Claudia Ramírez-Rentería, Laura C. Hernández-Ramírez
Best Practice & Research Clinical Endocrinology & Metabolism.2024; 38(3): 101892. CrossRef
Unlocking the Genetic Secrets of Acromegaly: Exploring the Role of Genetics in a Rare Disorder
Ioana Balinisteanu, Lavinia Caba, Andreea Florea, Roxana Popescu, Laura Florea, Maria-Christina Ungureanu, Letitia Leustean, Eusebiu Vlad Gorduza, Cristina Preda
Current Issues in Molecular Biology.2024; 46(8): 9093. CrossRef
Advancements in Molecular Diagnosis and Pharmacotherapeutic Strategies for Invasive Pituitary Adenomas
Dingkai Xu, Ling Wang, Maohua Zheng
Immunity, Inflammation and Disease.2024;[Epub] CrossRef
GNAS mutations suppress cell invasion by activating MEG3 in growth hormone–secreting pituitary adenoma
CHAO TANG, CHUNYU ZHONG, JUNHAO ZHU, FENG YUAN, JIN YANG, YONG XU, CHIYUAN MA
Oncology Research.2024; 32(6): 1079. CrossRef
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Endocrine Research
Suppression of Fibrotic Reactions of Chitosan-Alginate Microcapsules Containing Porcine Islets by Dexamethasone Surface Coating: Min Jung Kim, Heon-Seok Park, Ji-Won Kim, Eun-Young Lee, Marie Rhee, Young-Hye You, Gilson Khang, Chung-Gyu Park, Kun-Ho Yoon; Endocrinol Metab. 2021;36(1):146-156. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.879

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Background
The microencapsulation is an ideal solution to overcome immune rejection without immunosuppressive treatment. Poor biocompatibility and small molecular antigens secreted from encapsulated islets induce fibrosis infiltration. Therefore, the aims of this study were to improve the biocompatibility of microcapsules by dexamethasone coating and to verify its effect after xenogeneic transplantation in a streptozotocin-induced diabetes mice.
Methods
Dexamethasone 21-phosphate (Dexa) was dissolved in 1% chitosan and was cross-linked with the alginate microcapsule surface. Insulin secretion and viability assays were performed 14 days after microencapsulation. Dexa-containing chitosan-coated alginate (Dexa-chitosan) or alginate microencapsulated porcine islets were transplanted into diabetic mice. The fibrosis infiltration score was calculated from the harvested microcapsules. The harvested microcapsules were stained with trichrome and for insulin and macrophages.
Results
No significant differences in glucose-stimulated insulin secretion and islet viability were noted among naked, alginate, and Dexa-chitosan microencapsulated islets. After transplantation of microencapsulated porcine islets, nonfasting blood glucose were normalized in both the Dexa-chitosan and alginate groups until 231 days. The average glucose after transplantation were lower in the Dexa-chitosan group than the alginate group. Pericapsular fibrosis and inflammatory cell infiltration of microcapsules were significantly reduced in Dexa-chitosan compared with alginate microcapsules. Dithizone and insulin were positive in Dexa-chitosan capsules. Although fibrosis and macrophage infiltration was noted on the surface, some alginate microcapsules were stained with insulin.
Conclusion
Dexa coating on microcapsules significantly suppressed the fibrotic reaction on the capsule surface after transplantation of xenogenic islets containing microcapsules without any harmful effects on the function and survival of the islets.

Citations

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Xin Tan, Renwang Sheng, Liqin Ge
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Carbohydrate Polymers.2024; 323: 121425. CrossRef
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The Canadian Journal of Chemical Engineering.2024; 102(2): 561. CrossRef
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Immunoprotection Strategies in β‐Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation
Sarah Grimus, Victoria Sarangova, Petra B. Welzel, Barbara Ludwig, Jochen Seissler, Elisabeth Kemter, Eckhard Wolf, Asghar Ali
Advanced Science.2024;[Epub] CrossRef
A Case for Material Stiffness as a Design Parameter in Encapsulated Islet Transplantation
Courtney D. Johnson, Helim Aranda-Espinoza, John P. Fisher
Tissue Engineering Part B: Reviews.2023; 29(4): 334. CrossRef
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Li Chen, Fang Jiang, Haidan Xu, Yaoyao Fan, Cunbin Du
Biotechnology Letters.2023; 45(8): 1039. CrossRef
Advances in alginate encapsulation of pancreatic islets for immunoprotection in type 1 diabetes
Dinesh Chaudhary, Tiep Tien Nguyen, Simmyung Yook, Jee-Heon Jeong
Journal of Pharmaceutical Investigation.2023; 53(5): 601. CrossRef
Emerging strategies for beta cell transplantation to treat diabetes
Jesus Paez-Mayorga, Izeia Lukin, Dwaine Emerich, Paul de Vos, Gorka Orive, Alessandro Grattoni
Trends in Pharmacological Sciences.2022; 43(3): 221. CrossRef
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β cell replacement therapy for the cure of diabetes
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Modern pancreatic islet encapsulation technologies for the treatment of type 1 diabetes
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Russian Journal of Transplantology and Artificial Organs.2021; 23(4): 95. CrossRef

Case Reports

A Case of Diabetes Insipidus with Langerhans Cell Histiocytosis in Adult.: Jae Hoon Chung, Kwang Won Kim, Kyu Jeung Ahn, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Eun Mi Koh, Choon Kwan Kim, Mann Pyo Jung; J Korean Endocr Soc. 1996;11(3):330-335. Published online November 7, 2019

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Abstract PDF: In Langerhans cell histiocytosis, diabetes insipidus is the most common endocrinologic complication. We experienced a case of Langerhans cell histiocytosis, involving pituitary stalk and lung. The patient was a 43 year old male with complaint of polyuria and polydipsia. The water deprivation test was carried out to confirm the diagnosis of diabetes insipidus. We found multiple small cysts and nodules in HRCT of lung, and diagnosed Langerhans cell histiocytosis by transbronchial lung biopsy, The patient was managed conservatively with DDAVP nasal spray. The polyuria,polydipsia was relieved completely. After that, we follow up and observe closely the patients lung and pituitary lesion.

Two cases of 111Indium Pentetreotide Scan for the Pre- and Post-Operative Evaluation of Localization and Metastasis in Medullary Thyroid Carcinoma.: Jae Hoon Chung, Kwang Won Kim, Kyu Jeung Ahn, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kyoung Ah Kim, Yeun Sun Kim, Eun Mi Koh; J Korean Endocr Soc. 1996;11(1):85-92. Published online November 7, 2019

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Abstract PDF: Medullary carcinoma of the thyroid gland(MTC) constitutes approximatesly 3% to 10% of all malignant thyroid tumors. It appears in both familial and sporadic forms. Metastases are frequently present at diagnosis and are resistant to chemotherapy and radiotherapy. Surgical resection of the primary tumor and the metastases is the mainstay of treatment. Although MTC can be detected by elevated serum calcitonin, localization of residual or metastatic foci may be difficult. Many scintigraphic methods have been used for identification of the residual tumor or metastasis. However, most of them have either low sensitivity or low specificity. MTC frequently secretes somatostatin and may express somatostatin receptors. Recently, somatostatin-receptor imaging has been known to be useful for the detection of residual and recurrent medullary thyroid carcinoma. A 25 year-old woman who was dignosed as medullary carcinoma by biopsy of thyroid mass is presented. Thirteen years ago, she underwent left thyroidectomy due to thyroid cancer(MTC). Laboratory tests revealed an increase in the levels in serum CEA(CEA=557.6 ng/ml) and calcitonin(calcitonin= 720 pg/ml). The second patient, a 30 year-old female, complained of a palpable mass in the left anterior neck. Ten years ago, she underwent a right lobectomy of thyroid gland due to adenomatous goiter. Laboratory tests revealed an increase in the levels in serum CEA(CEA=617 ng/ml) and Calcitonin (Calcitonin=2,300 pg/ml). In both cases, pre- and postoperative In-111 pentetreotide scintigraphy were done and compared with "'I scintigraphy. In-111 pentetreotide scan may be useful for the localization of residual or metastatic medullary thyroid carcinoma. Further study is warranted to define the sensitivity and specificity of the technique.

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