Endocrinology and Metabolism

Original Articles

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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Abstract PDF Supplementary Material PubReader ePub: Background
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.

Mineral, Bone & Muscle
Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health: Ji Yeon Baek, Seong Hee Ahn, Il-Young Jang, Hee-Won Jung, Eunhye Ji, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Seongbin Hong, Beom-Jun Kim; Endocrinol Metab. 2025;40(1):73-81. Published online October 24, 2024; DOI: https://doi.org/10.3803/EnM.2024.2100

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Abstract PDF Supplementary Material PubReader ePub: Background
Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty—a condition that best reflects biological age—has not been thoroughly investigated.
Methods
We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.
Results
After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).
Conclusion
These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.

Thyroid
Clinicopathological Features and Molecular Signatures of Lateral Neck Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: Jinsun Lim, Han Sai Lee, Jin-Hyung Heo, Young Shin Song; Endocrinol Metab. 2024;39(2):324-333. Published online April 4, 2024; DOI: https://doi.org/10.3803/EnM.2023.1885

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Background
The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development.
Methods
We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining.
Results
Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group.
Conclusion
Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs.

Citations

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Prediction of lymph node metastasis in papillary thyroid carcinoma using non-contrast CT-based radiomics and deep learning with thyroid lobe segmentation: A dual-center study
Hao Wang, Xuan Wang, Yusheng Du, You Wang, Zhuojie Bai, Di Wu, Wuliang Tang, Hanling Zeng, Jing Tao, Jian He
European Journal of Radiology Open.2025; 14: 100639. CrossRef

Review Article

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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Yang Jong Lee, Jae Won Hong, Yongjae Kim, Jisup Kim, Chan Woo Kang, Min-Ho Lee, Ju Hyung Moon, Eui Hyun Kim, Cheol Ryong Ku, Eun Jig Lee
European Journal of Endocrinology.2025; 192(4): 335. CrossRef
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Tarik Elhadd, Shahd I Ibrahim, Elabbass Abdelmahmuod, Susan M Webb
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Zhenwei Li, Yinzi Wu, Guannan He, Renzhi Wang, Xinjie Bao
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A Study in Pituitary Neuroendocrine Tumors (PitNETs): Real-Life Data Amid Baseline and Serial CT Scans
Mihai Costachescu, Oana-Claudia Sima, Mihaela Stanciu, Ana Valea, Mara Carsote, Claudiu Nistor, Mihai-Lucian Ciobica
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Editorial: Prognostic factors in pituitary tumors: clinical, biochemical, imaging, and pathological aspects
Toru Tateno, Roxana-Ioana Dumitriu Stan, Stephanie Du Four
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Adaptive evaluation of gross total resection rates for endoscopic endonasal approach based on preoperative MRI morphological features of pituitary adenomas
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Original Articles

Mineral, Bone & Muscle
Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults: Sunghwan Ji, Kyunggon Kim, So Jeong Park, Jin Young Lee, Hee-Won Jung, Hyun Ju Yoo, Il-Young Jang, Eunju Lee, Ji Yeon Baek, Beom-Jun Kim; Endocrinol Metab. 2023;38(6):701-708. Published online October 18, 2023; DOI: https://doi.org/10.3803/EnM.2023.1783

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Background
Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults.
Methods
This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay.
Results
After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012).
Conclusion
These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF- 1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.

Citations

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Circulating BMP-7 Level is Independent of Sarcopenia in Older Asian Adults
Ahin Choi, Ji Yeon Baek, Eunhye Ji, Il-Young Jang, Hee-Won Jung, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Beom-Jun Kim
Annals of Geriatric Medicine and Research.2025; 29(1): 75. CrossRef
Unlocking diagnosis of sarcopenia: The role of circulating biomarkers – A clinical systematic review
F. Veronesi, F. Salamanna, V. Borsari, A. Ruffilli, C. Faldini, G. Giavaresi
Mechanisms of Ageing and Development.2024; 222: 112005. CrossRef

Diabetes, Obesity and Metabolism
Human Leukocyte Antigens and Biomarkers in Type 1 Diabetes Mellitus Induced by Immune-Checkpoint Inhibitors: Hidefumi Inaba, Yosuke Kaido, Saya Ito, Tomonao Hirobata, Gen Inoue, Takakazu Sugita, Yuki Yamamoto, Masatoshi Jinnin, Hiroaki Kimura, Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima, Takaaki Matsuoka; Endocrinol Metab. 2022;37(1):84-95. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1282

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Background
Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear.
Methods
In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021.
Results
Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset.
Conclusion
Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

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Fumika Kamitani, Yuichi Nishioka, Miyuki Koizumi, Hiroki Nakajima, Yukako Kurematsu, Sadanori Okada, Shinichiro Kubo, Tomoya Myojin, Tatsuya Noda, Tomoaki Imamura, Yutaka Takahashi
Journal of Diabetes Investigation.2025; 16(2): 334. CrossRef
Immune checkpoint inhibitor-related diabetes mellitus associated with high signal intensity in diffusion-weighted magnetic resonance imaging of the pancreas at an early clinical stage
Masaki Suzuki, Yushi Hirota, Shin Urai, Masaaki Yamamoto, Keitaro Sofue, Wataru Ogawa
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Durvalumab-induced Type 1 Diabetes in a Patient With Pre-existing GADA-positive Diabetes and Preserved Insulin Secretion
Nobuhiro Nakatake, Megumi Matsuda, Hiroki Kontani
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Seok Jun Park, Seungwon Yang, Suhyun Lee, Sung Hwan Joo, Taemin Park, Dong Hyun Kim, Hyeonji Kim, Soyun Park, Jung-Tae Kim, Won Gun Kwack, Sung Wook Kang, Yun-Kyoung Song, Jae Myung Cha, Sang Youl Rhee, Eun Kyoung Chung
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Yuma Motomura, Shin Urai, Yushi Hirota, Naoki Takegawa, Hironori Bando, Masaaki Yamamoto, Hidenori Fukuoka, Masahiro Tsuda, Wataru Ogawa
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Thyroid
Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis: Mijin Kim, Chae Hwa Kwon, Min Hee Jang, Jeong Mi Kim, Eun Heui Kim, Yun Kyung Jeon, Sang Soo Kim, Kyung-Un Choi, In Joo Kim, Meeyoung Park, Bo Hyun Kim; Endocrinol Metab. 2021;36(5):1086-1094. Published online October 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1132

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Background
Early identification of patients with high-risk papillary thyroid microcarcinoma (PTMC) that is likely to progress has become a critical challenge. We aimed to identify somatic mutations associated with lateral neck lymph node (LN) metastasis (N1b) in patients with PTMC.
Methods
Whole-exome sequencing (WES) of 14 PTMCs with no LN metastasis (N0) and 13 N1b PTMCs was performed using primary tumors and matched normal thyroid tissues.
Results
The mutational burden was comparable in N0 and N1b tumors, as the median number of mutations was 23 (range, 12 to 46) in N0 and 24 (range, 12 to 50) in N1b PTMC (P=0.918). The most frequent mutations were detected in PGS1, SLC4A8, DAAM2, and HELZ in N1b PTMCs alone, and the K158Q mutation in PGS1 (four patients, Fisher’s exact test P=0.041) was significantly enriched in N1b PTMCs. Based on pathway analysis, somatic mutations belonging to the receptor tyrosine kinase-RAS and NOTCH pathways were most frequently affected in N1b PTMCs. We identified four mutations that are predicted to be pathogenic in four genes based on Clinvar and Combined Annotation-Dependent Depletion score: BRAF, USH2A, CFTR, and PHIP. A missense mutation in CFTR and a nonsense mutation in PHIP were detected in N1b PTMCs only, although in one case each. BRAF mutation was detected in both N0 and N1b PTMCs.
Conclusion
This first comprehensive WES analysis of the mutational landscape of N0 and N1b PTMCs identified pathogenic genes that affect biological functions associated with the aggressive phenotype of PTMC.

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Transcriptome sequencing revealed that lymph node metastasis of papillary thyroid microcarcinoma is associated with high THBS4 expression and PDGFRA+ cancer-associated fibroblasts
LeYin Hu, Yi Lin, JingYu Zheng, Li Wan, Rui Zhao, Yi Ma, JianMin Li
Frontiers in Oncology.2025;[Epub] CrossRef
What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?
Bobby White, Pawel Swietach
Pflügers Archiv - European Journal of Physiology.2024; 476(4): 673. CrossRef
Comprehensive Long-Read Sequencing Analysis Discloses the Transcriptome Features of Papillary Thyroid Microcarcinoma
Yanqiang Wang, Binbin Zou, Yanyan Zhang, Jin Zhang, Shujing Li, Bo Yu, Zhekun An, Lei Li, Siqian Cui, Yutong Zhang, Jiali Yao, Xiuzhi Shi, Jing Liu
The Journal of Clinical Endocrinology & Metabolism.2024; 109(5): 1263. CrossRef
Feasibility of whole‐exome sequencing in fine‐needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations
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Diabetes, Obesity and Metabolism
Association of Protein Z with Prediabetes and Type 2 Diabetes: Yun-Ui Bae, Ji Hong You, Nan Hee Cho, Leah Eunjung Kim, Hye Min Shim, Jae-Hyung Park, Ho Chan Cho; Endocrinol Metab. 2021;36(3):637-646. Published online June 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.962

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Background
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease. Early detection of prediabetes is important to reduce the risk of T2DM. Some cytokines are known to be associated with T2DM. Therefore, we aimed to identify cytokines as novel biomarkers of glucose dysmetabolism.
Methods
The first stage of the study included 43 subjects (13 subjects with newly diagnosed T2DM, 13 with prediabetes, and 16 with normoglycemia) for cytokine microarray analysis. Blood samples of the subjects were assessed for 310 cytokines to identify potential indicators of prediabetes. The second stage included 142 subjects (36 subjects with T2DM, 35 with prediabetes, and 71 with normoglycemia) to validate the potential cytokines associated with prediabetes.
Results
We identified 41 cytokines that differed by 1.5-fold or more in at least one out of the three comparisons (normoglycemia vs. prediabetes, normoglycemia vs. T2DM, and prediabetes vs. T2DM) among 310 cytokines. Finally, we selected protein Z (PROZ) and validated this finding to determine its association with prediabetes. Plasma PROZ levels were found to be decreased in patients with prediabetes (1,490.32±367.19 pg/mL) and T2DM (1,583.34±465.43 pg/mL) compared to those in subjects with normoglycemia (1,864.07±450.83 pg/mL) (P<0.001). There were significantly negative correlations between PROZ and fasting plasma glucose (P=0.001) and hemoglobin A1c (P=0.010).
Conclusion
PROZ levels were associated with prediabetes and T2DM. We suggest that PROZ may be a promising biomarker for the early detection of prediabetes. Further large-scale studies are needed to evaluate the relationship and mechanism between PROZ and prediabetes and T2DM.

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Ronglin Li, Zhenniu Lei, Zhaoke Wen, Yifan Zhou, Yunzhi Ma, Junqi Qin, Xiaoyan Huang, Shuping Huang, Shucong Peng, Shengjing Liang, Yonglong Zhong
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Endocrine Research
Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults: Da Ae Kim, So Jeong Park, Jin Young Lee, Jeoung Hee Kim, Seungjoo Lee, Eunju Lee, Il-Young Jang, Hee-Won Jung, Jin Hoon Park, Beom-Jun Kim; Endocrinol Metab. 2021;36(2):455-465. Published online April 14, 2021; DOI: https://doi.org/10.3803/EnM.2020.942

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Background
The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults.
Methods
Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline.
Results
Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index.
Conclusion
Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.

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MEGF6 knockdown ameliorates lenvatinib-induced muscle differentiation suppression and enhances the antitumor effect of lenvatinib on hepatocellular carcinoma
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C–C motif chemokine CCL11 is a novel regulator and a potential therapeutic target in non-alcoholic fatty liver disease
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Clinical Study
Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer: Eun Jeong Ban, Daham Kim, Jin Kyong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung, Kunhong Kim; Endocrinol Metab. 2021;36(1):96-105. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.819

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Background
Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV^600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker.
Methods
LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV^600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results.
Results
LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV^600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV^600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages.
Conclusion
LDHA overexpression is associated with the BRAFV^600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

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Review Articles

Obesity and Metabolism
Noninvasive Evaluation of Nonalcoholic Fatty Liver Disease: Dae Ho Lee; Endocrinol Metab. 2020;35(2):243-259. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.243

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Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver diseases and can progress to advanced fibrosis and end-stage liver disease. Thus, intensive research has been performed to develop noninvasive methods for the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis. Currently, no single noninvasive tool covers all of the stages of pathologies and conditions of NAFLD, and the cost and feasibility of known techniques are also important issues. Blood biomarkers for NAFLD may be useful to select subjects who need ultrasonography (US) screening for NAFLD, and noninvasive tools for assessing fibrosis may be helpful to exclude the probability of significant fibrosis and to predict advanced fibrosis, thus guiding the decision of whether to perform liver biopsy in patients with NAFLD. Among various methods, magnetic resonance-based methods have been shown to perform better than other methods in assessing steatosis as well as in detecting hepatic fibrosis. Many genetic markers are associated with the development and progression of NAFLD. Further well-designed studies are needed to determine which biomarker panels, imaging studies, genetic marker panels, or combinations thereof perform well for diagnosing NAFLD, differentiating NASH and fibrosis, and following-up NAFLD, respectively.

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Intact ketogenesis predicted reduced risk of moderate-severe metabolic-associated fatty liver disease assessed by liver transient elastography in newly diagnosed type 2 diabetes
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Diabetes & Metabolism.2024; 50(3): 101534. CrossRef
Noninvasive Tests to Assess Fibrosis and Disease Severity in Metabolic Dysfunction-Associated Steatotic Liver Disease
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A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease
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Diabetes & Metabolism Journal.2024; 48(4): 740. CrossRef
Evaluating the role of IER3+ macrophages in the prognosis of liver fibrosis by bulk and single-cell transcriptional analyses
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Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
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Non-invasive diagnosis and monitoring of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis
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The Impact of Insulin Resistance on Hepatic Fibrosis among United States Adults with Non-Alcoholic Fatty Liver Disease: NHANES 2017 to 2018
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Mauro Viganò, Nicola Pugliese, Federica Cerini, Federica Turati, Vincenzo Cimino, Sofia Ridolfo, Simone Rocchetto, Francesca Foglio, Maria Terrin, Carlo La Vecchia, Maria Grazia Rumi, Alessio Aghemo
International Journal of Molecular Sciences.2022; 23(20): 12489. CrossRef
MAFLD vs. NAFLD: shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy
Ying-Xin Xian, Jian-Ping Weng, Fen Xu
Chinese Medical Journal.2021; 134(1): 8. CrossRef
Prognostic accuracy of FIB‐4, NAFLD fibrosis score and APRI for NAFLD‐related events: A systematic review
Jenny Lee, Yasaman Vali, Jerome Boursier, Rene Spijker, Quentin M. Anstee, Patrick M. Bossuyt, Mohammad H. Zafarmand
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Serum syndecan‐4 is associated with nonalcoholic fatty liver disease
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Non-Laboratory-Based Simple Screening Model for Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Developed Using Multi-Center Cohorts
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Bone Metabolism
Potential Biomarkers to Improve the Prediction of Osteoporotic Fractures: Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh; Endocrinol Metab. 2020;35(1):55-63. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.55

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Osteoporotic fracture (OF) is associated with high disability and morbidity rates. The burden of OF may be reduced by early identification of subjects who are vulnerable to fracture. Although the current fracture risk assessment model includes clinical risk factors (CRFs) and bone mineral density (BMD), its overall ability to identify individuals at high risk for fracture remains suboptimal. Efforts have therefore been made to identify potential biomarkers that can predict the risk of OF, independent of or combined with CRFs and BMD. This review highlights the emerging biomarkers of bone metabolism, including sphongosine-1-phosphate, leucine-rich repeat-containing 17, macrophage migration inhibitory factor, sclerostin, receptor activator of nuclear factor-κB ligand, and periostin, and the importance of biomarker risk score, generated by combining these markers, in enhancing the accuracy of fracture prediction.

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Nobiletin promotes osteogenic differentiation of human osteoblastic cell line (MG-63) through activating the BMP-2/RUNX-2 signaling pathway
Ying Pang, Lili Liu, Hong Mu, Vishnu Priya Veeraraghavan
Saudi Journal of Biological Sciences.2021; 28(9): 4916. CrossRef

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