European Journal of Endocrinology最新文献

{"title":"Additive effects of ALXN2420, a GH receptor antagonist, and octreotide on IGF1 suppression in vivo.","authors":"Guillaume Ravel, Xavier Gaume, Corentin Berardet, Clémentine Chalmey, Haruaki Kurasaki, Tatsuya Tomiyama, Patrick C Reid, David Duracher, Rakesh Datta, Myriam Aouadi, Michael D Culler","doi":"10.1093/ejendo/lvaf043","DOIUrl":"10.1093/ejendo/lvaf043","url":null,"abstract":"<p><strong>Objective: </strong>Acromegaly is an endocrine disorder caused by the hypersecretion of growth hormone (GH) by a benign tumor of the pituitary that leads to insulin-like growth factor-1 (IGF1) overproduction. In most patients, somatostatin analogs (SSAs), the current first-line medical therapy for acromegaly, do not normalize IGF1 levels. This study aims to investigate the pre-clinical efficacy of ALXN2420, a novel, small peptide antagonist of the growth hormone receptor (GHR), being developed as a combination therapy to SSAs to further suppress and normalize IGF1 levels.</p><p><strong>Design: </strong>In vitro and in vivo experiments were performed to investigate the efficacy of ALXN2420 in antagonizing the GHR and in reducing circulating IGF1 levels.</p><p><strong>Methods: </strong>The binding affinity of ALXN2420 to GHR was determined by Surface Plasmon Resonance (SPR), and inhibition of GH-induced GHR activation was investigated in vitro in primary hepatocytes. The efficacy of ALXN2420 in suppressing IGF1 levels was evaluated in rats and dogs. The ability of ALXN2420 to reduce growth was determined in the juvenile rat model. Ultimately, the effect of combining ALXN2420 with a SSA in suppressing IGF1 was examined in rats.</p><p><strong>Results: </strong>ALXN2420 bound to the human GHR and inhibited its activation by GH in vitro. In vivo, ALXN2420 administration efficiently reduced IGF1 levels, which was associated with reduced growth in juvenile rats. Importantly, when combined with a SSA, ALXN2420 demonstrated an additive effect on IGF1 reduction.</p><p><strong>Conclusion: </strong>These results support the investigation of ALXN2420 as a combination therapy for the treatment of patients with acromegaly inadequately controlled by SSAs.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"299-307"},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delphi panel consensus on recommendations for thromboprophylaxis of venous thromboembolism in endogenous Cushing's syndrome: a position statement.","authors":"Kristina Isand, Hiroshi Arima, Jerome Bertherat, Olaf M Dekkers, Richard A Feelders, Maria Fleseriu, Monica R Gadelha, Jose Miguel Hinojosa-Amaya, Niki Karavitaki, Frederikus A Klok, Ann McCormack, John Newell-Price, Sue Pavord, Martin Reincke, Saurabh Sinha, Elena Valassi, John Wass, Alberto M Pereira Arias","doi":"10.1093/ejendo/lvaf017","DOIUrl":"10.1093/ejendo/lvaf017","url":null,"abstract":"<p><p>The objective of this study was to establish recommendations for thromboprophylaxis in patients with endogenous Cushing's syndrome (CS), addressing the elevated risk of venous thromboembolism (VTE) associated with hypercortisolism. A Delphi method was used, consisting of 4 rounds of voting and subsequent discussions. The panel included 18 international experts from 11 countries and 4 continents. Consensus was defined as ≥75% agreement among participants. Recommendations were structured into the following categories: thromboprophylaxis, perioperative management, and VTE treatment. Consensus was reached on several critical areas, resulting in 14 recommendations. Key recommendations include: thromboprophylaxis should be considered at time of CS diagnosis and continued for 3 months after biochemical remission, provided there are no obvious contraindications. The standard weight-based prophylactic dose of low molecular-weight heparin is the preferred agent for thromboprophylaxis in patients with CS. Additionally, perioperatively and around inferior petrosal sinus sampling, thromboprophylaxis should be reconsidered if not already initiated at diagnosis. For VTE treatment, extended thromboprophylaxis is advised continuing for 3 months after Cushing is resolved. These Delphi consensus-based recommendations aim to standardize care practices and enhance patient outcomes in CS by providing guidance on thromboprophylaxis, including its initiation and continuation across various disease states, as well as the preferred agents to use. The panel also highlighted key areas for further research, particularly regarding the use of direct oral anticoagulants in CS and the management of mild CS and mild autonomous cortisol secretion. Additionally, the optimal duration of anticoagulant prophylaxis following curative treatment remains uncertain.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"R17-R27"},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of cardiovascular risk factors and the risk for cardiovascular events in a Caucasian population with polycystic ovary syndrome.","authors":"Alessandra Gambineri, Simona Rosa, Srdjan Pandurevic, Carolina Cecchetti, Laura Rotolo, Paola Dionese, Elisabetta Belardinelli, Beatrice Solmi, Guido Zavatta, Flaminia Fanelli, Paola Rucci, Francesco Angeli, Matteo Armillotta, Luca Bergamaschi, Enrico Gallitto, Mauro Gargiulo, Djuro Macut, Carmine Pizzi, Uberto Pagotto","doi":"10.1093/ejendo/lvaf027","DOIUrl":"10.1093/ejendo/lvaf027","url":null,"abstract":"<p><strong>Objective: </strong>To estimate the risk of cardiovascular (CV) events (primary aim) and to evaluate the long-term variation in CV risk factors in a Caucasian population of women with polycystic ovary syndrome (PCOS).</p><p><strong>Design: </strong>Matched cohort prospective study based on 10 years of follow-up.</p><p><strong>Methods: </strong>One hundred twenty Caucasian women with PCOS diagnosed by the National Institutes of Health criteria in reproductive age were assessed at baseline (2009) and at the end of follow-up (2020) for major and minor CV events and CV risk factors. Five controls were exactly matched by age and the presence/absence of type 2 diabetes with each participant at baseline (total number = 600) and followed up to evaluate the relative risk of PCOS for CV events. Change in epicardial fat thickness (EFT) was also analysed.</p><p><strong>Results: </strong>The mean age of patients with PCOS at follow-up was 51.9 ± 7.7 years. No major CV events were detected in PCOS patients (0% vs. 2% among controls), and the incidence of any minor CV events was 4.2% vs. 2.3% among controls (P = .340). The percentage of most CV risk factors (obesity, type 2 diabetes, hypertension, dyslipidaemia, and carotid intima media thickness ≥1 mm with or without plaques with non-critical stenosis) increased. By contrast, both short- and long-axis EFTs and smoking decreased markedly.</p><p><strong>Conclusions: </strong>Caucasian patients with PCOS do not have an increased risk for CV events during the late reproductive or early post-menopausal period, despite the increase in most CV risk factors, except for EFT that markedly decreases. Further studies are needed to determine the role of EFT on CV risk in PCOS.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"210-219"},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding lymph node skip metastasis: impact on long-term outcomes in stage T1 papillary thyroid carcinoma.","authors":"Sijia Cai, Chao Qin, Meilin Liu, Yanxi Liu, Haitao Tang, Weibo Xu, Min Yin, Qinghai Ji, Tian Liao, Yu Wang","doi":"10.1093/ejendo/lvaf050","DOIUrl":"10.1093/ejendo/lvaf050","url":null,"abstract":"<p><strong>Background: </strong>Skip metastasis of lateral cervical lymph nodes not uncommonly occurs in early papillary thyroid carcinoma (PTC), which represents a heterogeneous metastasis type. Currently, few studies report on the relationship between skip metastasis and prognosis or propose treatment recommendations.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on patients with unilateral T1-stage PTC who underwent lobectomy between 2007 and 2015. Patients with skipping N1b (sN1b) stage were included, and propensity score matching (PSM) was applied to incorporate patients from both N1a and N1b stages for comparison. Kaplan-Meier method was employed to compare recurrence-free survival (RFS) among different groups, and lymph node metastasis patterns in sN1b group as well as their impacts on prognosis were evaluated.</p><p><strong>Results: </strong>The initial cohort comprised 1188 patients, and after adjusting for baseline clinicopathological data and follow-up duration, a total of 372 patients were included with an average follow-up time of 82 months. The recurrence rates in the N1a, sN1b, and N1b groups after PSM were 8.9%, 11.3%, and 12.9%, respectively. Notably, RFS did not differ significantly between sN1b and N1a (P = .65) or N1b (P = .66). Furthermore, the number of positive lymph nodes in the sN1b group was comparable to N1a group (P = .77) but significantly lower than N1b group (P < .0001). Remarkably, the risk stratification based on the lymph node positivity rate (LNPR) in the sN1b group demonstrated a strong prognostic discrimination (P = .0067).</p><p><strong>Conclusion: </strong>The RFS among stage T1 PTC patients with sN1b stage was comparable to those with N1a and N1b stages. LNPR risk stratification emerged as a significant prognostic factor.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"318-326"},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response by Yuk et al. to letter regarding article, \"Association of menopausal hormone therapy with risk of cardiovascular disease in Korean women\".","authors":"Jin-Sung Yuk, Gwang Sil Kim, Dong-Gil Kim, Young Sup Byun, Myoung-Hwan Kim, Sang-Hee Yoon, Gwan Hee Han, Byung Gyu Kim","doi":"10.1093/ejendo/lvaf041","DOIUrl":"10.1093/ejendo/lvaf041","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"L14-L15"},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mild autonomous cortisol secretion in patients with aldosterone-producing adenoma and risk for cardiac remodeling and diastolic dysfunction.","authors":"Cheng-Hsuan Tsai, Che-Wei Liao, Xue-Ming Wu, Zheng-Wei Chen, Chien-Ting Pan, Yi-Yao Chang, Bo-Ching Lee, Chia-Hung Chou, Chin-Chen Chang, Vin-Cent Wu, Chi-Sheng Hung, Anand Vaidya, Yen-Hung Lin","doi":"10.1093/ejendo/lvaf007","DOIUrl":"10.1093/ejendo/lvaf007","url":null,"abstract":"<p><strong>Background: </strong>Mild autonomous cortisol secretion (MACS) is common in adrenal adenomas, including patients with primary aldosteronism (PA) with aldosterone-producing adenomas (APA). This study investigated the impact of MACS on cardiac remodeling and diastolic dysfunction in patients with APA.</p><p><strong>Methods: </strong>We prospectively enrolled 483 patients with APA. MACS was defined as a cortisol level >1.8 μg/dL after an overnight dexamethasone-suppression test (DST). Clinical, biochemical, and echocardiographic data were collected at baseline and one-year following targeted treatments.</p><p><strong>Results: </strong>In this prospective cohort, 21% of patients with APA had concurrent MACS. Patients with MACS were older, had a higher prevalence of diabetes, larger adrenal tumor size, higher left ventricular mass index (LVMI), and worse diastolic function (E/e'). Multivariable linear regression analysis showed that concurrent MACS with APA was an independent risk factor for higher LVMI and worse E/e'. Among patients who underwent adrenalectomy, both those with and without MACS showed significant improvements in LVMI and E/e'. In contrast, among patients who received mineralocorticoid receptor antagonist (MRA) treatment, significant LVMI improvement was only observed in patients without MACS. MRA therapy did not improve E/e' regardless of the presence or absence of MACS.</p><p><strong>Conclusions: </strong>The presence of MACS in patients with PA was associated with worse cardiac hypertrophy and diastolic dysfunction. Surgical adrenalectomy was able to effectively reverse cardiac remodeling in patients with PA and concurrent MACS; however, MRA therapy was not associated with significant improvements in cardiac function. These findings highlight the independent deleterious effects of cortisol on cardiovascular disease in PA.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"81-90"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormonal regulation of human adipose tissue lipolysis: impact of adipose GIP system in overweight and obesity.","authors":"Sebastian Brachs, Dominik Soll, Finja Beer, Nadine Huckauf, Anish Konkar, Joachim Spranger, Hartmut Rütten, Knut Mai","doi":"10.1093/ejendo/lvae151","DOIUrl":"https://doi.org/10.1093/ejendo/lvae151","url":null,"abstract":"<p><strong>Objective: </strong>Given the promising effects of GLP-1/GIP/glucagon receptor triagonists on weight loss in animals and humans, improved understanding of underlying mechanism is required. We investigated a direct lipolytic effect of a specific GLP-1/GIP/glucagon receptor triagonist on human adipose tissue to disentangle central and peripheral effects as potential drivers of weight loss.</p><p><strong>Design and methods: </strong>Isolated primary adipocytes from subcutaneous adipose tissue biopsies of 22 non-diabetic subjects [63.0 (57.0-69.5) years] were incubated with increasing concentrations of isoprenaline, GLP-1, GIP, glucagon, or a GLP-1/GIP/glucagon receptor triagonist. Glycerol concentration was measured following stimulation to assess lipolysis. mRNA expression of adipose tissue receptors was analyzed in parallel.</p><p><strong>Results: </strong>Glycerol concentration only increased by isoprenaline, GIP (+13%), and GLP-1/GIP/glucagon receptor triagonist (+28%) but not by GLP-1 or glucagon. This effect was not related to age or body mass index (BMI). Higher adipose tissue GIP receptor mRNA expression was related to elevated glycerol release after GIP and GLP-1/GIP/glucagon receptor triagonist stimulation.</p><p><strong>Conclusions: </strong>Direct lipolytic effects of GIP seem to exist in human subcutaneous adipose tissue. This might be targetable by multiple receptor agonists, especially with a high GIP receptor affinity. Such a mechanism can potentiate the beneficial effect on weight loss and will therefore represent a promising target of future research.</p><p><strong>Clinical trial registration number: </strong>The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 2","pages":"91-99"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Descriptive analysis and outcomes of PitNETs treated surgically during pregnancy and postpartum.","authors":"Cindy Odot, Mathilde Brière, Chiara Villa, Théophraste Henry, Stephan Gaillard, Philippe Caron, Lionel Groussin, Yves Reznik, Anne Rod, Camille Ghorra, Marie-Laure Raffin-Sanson, Bertrand Baussart, Mirella Hage","doi":"10.1093/ejendo/lvaf018","DOIUrl":"10.1093/ejendo/lvaf018","url":null,"abstract":"<p><strong>Objective: </strong>Data on pituitary neuroendocrine tumours (PitNETs) surgically treated during pregnancy are limited, and no studies have compared these cases to those treated in non-pregnant women. This study aimed to describe the clinical, radiological, and histological profiles of patients treated surgically for PitNETs during pregnancy and evaluate long-term prognosis.</p><p><strong>Design: </strong>This study was multicentric, observational, and retrospective.</p><p><strong>Methods: </strong>We included 10 patients from 5 university hospitals who underwent surgical treatment for PitNETs during pregnancy or within 12 months postpartum, along with 30 matched non-pregnant controls treated surgically for PitNETs. Clinical and histological data, as well as progression-free survival without additional treatment, were compared between pregnant and non-pregnant patients.</p><p><strong>Results and conclusions: </strong>Among the 10 PitNETs, 4 were corticotropic, 2 gonadotropic, 2 lactotropic, and 2 somatotropic. The primary surgical indication (tumour syndrome with or without failure of medical treatment) was similar between the two groups: 7/10 vs 19/30 (P = 1.00). There was no statistically significant difference in volume (P = .072) or radiological invasion markers (optic chiasm compression, P = .059, and cavernous sinus invasion, P = .274). However, PitNETs in pregnant women showed higher mitotic activity (P = .038) and were more frequently classified as grade 2b (Trouillas clinicopathological classification; P = .049). The need for second-line treatment was also more frequent (P = .005). PitNETs requiring surgical treatment during pregnancy are characterized by increased proliferative activity and progression after surgery. Despite this, the long-term prognosis remains favourable. These results need confirmation in a larger study.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"150-158"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype and genotype of 23 patients with hypopituitarism and pathogenic GLI2 variants.","authors":"Karine Aouchiche, Camille Charmensat, Pertuit Morgane, Cécile Teinturier, Patricia Bretones, Aude Brac de la Perriere, Valérie Layet, Natacha Bouhours-Nouet, Marie-Christine Vantyghem, Elsa Haine, Marie-Laure Nunes-Sanchez, Odile Camard, Sabine Baron, Frederic Castinetti, Anne Barlier, Thierry Brue, Rachel Reynaud, Alexandru Saveanu","doi":"10.1093/ejendo/lvaf015","DOIUrl":"10.1093/ejendo/lvaf015","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the phenotype and genotype of patients with congenital hypopituitarism (CH) and pathogenic (P) GLI2 variants.</p><p><strong>Methods: </strong>A large cohort of patients with hypopituitarism was screened for GLI2 variants using a next-generation sequencing panel. Genotype-phenotype correlations were then assessed using GENHYPOPIT phenotypic data.</p><p><strong>Results: </strong>Of the 39 GLI2 variants identified in 717 index cases, 17 were classified as pathogenic and likely pathogenic. All these GLI2 variants were identified in 23 patients (17 index cases and 6 relatives) with associated pituitary stalk interruption syndrome or extrapituitary manifestations. GLI2 variants were the most frequently identified genetic cause in patients with syndromic hypopituitarism (68%): 88% (15/17) of mutations were truncating variants, and 45% were de novo. Most patients with a GLI2 variant (21/23, 91%) had hypopituitarism, including 21.7% (5/23) presenting isolated growth hormone deficiency. Two patients had Kallmann syndrome. Pituitary morphological abnormalities were present in 84% of the patients with P GLI2 variants (index cases and affected relatives). The remaining signs included neurocognitive disorders (38%), hexadactyly (27%), cardiac septal defects, and renal/vesical abnormalities. A possible digenic origin (GLI2/HESX1) is proposed in one family.</p><p><strong>Conclusion: </strong>In this large multicentric international cohort, GLI2 was the most frequently identified genetic cause of syndromic CH with constant association of pituitary stalk interruption syndrome or extrapituitary clinical features. In addition to polydactyly and neurocognitive disorders, cardiac and renal abnormalities were also frequently observed and should be investigated further. The variable expression of GLI2-associated phenotypes justifies further research in this area.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"110-118"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new broom sweeps clean: CLDN16 surpasses the BRAF-V600E mutation as an unrivaled biomarker in papillary thyroid cancer.","authors":"Yefeng Cai, Yawen Guo, Wenli Ma, Pu Cheng, Liehao Jiang, Shuyan Shen, Fahuan Song, Lei Zhu, Yiqun Hu, Yao Chen, Yanting Duan, Xiujun Cai, Quan Li, Guowan Zheng, Minghua Ge","doi":"10.1093/ejendo/lvaf003","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf003","url":null,"abstract":"<p><strong>Objective: </strong>This study assessed CLDN16 as a potential replacement or improvement biomarker for papillary thyroid cancer (PTC), addressing the limitations associated with the prevalently used BRAF-V600E mutation.</p><p><strong>Design: </strong>Database analyses, tissue validation, RNA sequencing, and functional assays were conducted to evaluate CLDN16 as a PTC biomarker and its clinical application.</p><p><strong>Methods: </strong>CLDN16 expression was examined in PTC and normal thyroid/para-tumor tissues and compared across various cancer types. We evaluated diagnostic accuracy, stability in primary and metastatic sites, and associations with aggressive features. Knockdown experiments were performed to investigate the impact on PTC cell behavior. Additionally, we developed a support vector machine model for diagnosing malignant and high-risk PTCs.</p><p><strong>Results: </strong>CLDN16 demonstrated high specificity for PTC, with positive detection rates (88.0% in The Cancer Genome Atlas [TCGA] and 88.3% in our center) significantly surpassing BRAF-V600E (47.5% in TCGA and 74.3% in our center). This resulted in superior diagnostic accuracy (ROC-CLDN16 = 0.922 vs ROC-BRAF-V600E = 0.742 in TCGA). CLDN16 exhibited stable expression across primary and metastatic sites and was associated with aggressive features, including extrathyroidal extension and lymph node metastasis. CLDN16 knockdown inhibited migration, invasion, and iodine uptake in PTC cells. Clinically, CLDN16 effectively identified malignancy in BRAF wild patients (94.2%), and combined with BRAF-V600E, achieved 96.9% accuracy. The incorporation of CLDN16 into PTC molecular typing facilitated precise high-risk identification (92.0% accuracy in the training set and 100% in the validation set).</p><p><strong>Conclusions: </strong>CLDN16 presents a promising biomarker that could surpass BRAF-V600E, offering effective clinical utility and revolutionizing PTC molecular typing for precise high-risk identification.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 2","pages":"128-140"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}