Endocrine Connections最新文献

{"title":"Gene expression profiles associated with stimulus-responsive insulin secretion in insulinoma.","authors":"Kenji Sugawara, Yuko Okada, Tomokazu Matsuda, Yushi Hirota, Shun-Ichiro Asahara, Kazuhiko Sakaguchi, Wataru Ogawa","doi":"10.1530/EC-26-0322","DOIUrl":"10.1530/EC-26-0322","url":null,"abstract":"<p><p>Insulinoma is a functional pancreatic neuroendocrine tumor that usually causes fasting hypoglycemia through inappropriate autonomous insulin secretion. However, some insulinomas show postprandial or stimulus-induced hypoglycemia, suggesting that some tumors retain the ability to respond to physiological stimuli. We examined four patients with confirmed insulinoma who showed different clinical patterns of hypoglycemia and integrated clinical stimulation tests with DNA microarray analysis. Insulin secretory dynamics were assessed using an oral glucose tolerance test, meal tolerance test, and glucagon stimulation test, as clinically indicated. Among the four cases, Case 1 showed no clear fasting hypoglycemia but developed hypoglycemia after meals and oral glucose loading, accompanied by marked insulin secretion. In this case, insulin or C-peptide increased markedly after glucose, meal, and glucagon stimulation. In contrast, the other three cases showed relatively weak insulin secretory responses to stimulation. During the fasting test, Cases 3 and 4 developed hypoglycemia early, whereas Case 2 showed a prolonged time to hypoglycemia. Transcriptomic analysis showed that, by hierarchical clustering, Case 1 was clearly separated from Cases 3 and 4, whereas Case 2 was relatively close to Case 1. Case 1 showed relatively preserved expression of genes involved in glucose sensing, ATP-sensitive potassium channel function, incretin/cAMP signaling, exocytosis, and β-cell differentiation. In contrast, cases with predominant fasting hypoglycemia showed higher expression of hexokinase 1 and stress-response genes. These findings suggest that clinical heterogeneity in insulinoma may reflect differences in β-cell-like stimulus-response mechanisms, glucose sensing, stress responses, and differentiation status.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dampened HPG axis activity and altered ovarian gene transcription in Dummerstorf high-fertility mouse line FL2.","authors":"Carolin L M Ludwig, Simon Bohleber, Anja Baufeld, Eva K Wirth, Martina Langhammer, Ulrich Schweizer, Marten Michaelis, Joachim M Weitzel","doi":"10.1530/EC-26-0242","DOIUrl":"10.1530/EC-26-0242","url":null,"abstract":"<p><p>Animal models of enhanced fertility are rare, as most genetically modified mouse models with reproductive phenotype display subfertility or infertility. Here, we describe the ovarian phenotype of the Dummerstorf line 2 (FL2) mouse strain, which exhibits high fertility and has been selectively bred for increased fertility over more than 190 generations. This long-term selection, outbred mouse line almost doubled the litter size to 21.5 (FL2) compared with 11.3 (unselected control line, ctrl), without showing any signs of growth retardation in the offspring. Here, we show that FL2 females ovulate 25.0 oocytes per cycle compared with 13.2 in ctrl. FL2 mice remain in the estrus phase for a shorter period during a 12-day observation period. Follicle-stimulating hormone (FSH) levels are decreased, both in estrus and diestrus, compared with ctrl, whereas luteinizing hormone levels are unaffected. The mRNA expression levels in the pituitary gland correspond to the gonadotropin levels in the blood. Progesterone levels are decreased in estrus in FL2. Hypothalamic expression levels of gonadotropin-releasing hormone (GnRH) are decreased in diestrus. Holistic gene expression analysis indicates complex and differential regulation in estrus and diestrus in ovaries of FL2 compared with ctrl. In particular, genes of the TGF-β pathway (such as Bmp3, Bmp7, and Inhba) and the Wnt pathway (such as Sfrp4 and Mkrn1) are differentially expressed in ovaries of FL2 females. These data indicate that reduced activity of the hypothalamic-pituitary-gonadal axis (in particular, lower levels of GnRH, FSH, and progesterone), combined with altered gene transcription in the ovaries, leads to higher ovulation rates in order to achieve the breeding objective of improved fertility.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Group education improves self-management of adrenal insufficiency in patients and their relative.","authors":"Anna-Karin Åkerman, Charlotte Höybye, Katarina Berinder, Maria Petersson, Tim Spelman, Jeanette Wahlberg, Per Dahlqvist, Sophie Bensing","doi":"10.1530/EC-26-0121","DOIUrl":"10.1530/EC-26-0121","url":null,"abstract":"<p><strong>Objective: </strong>Self-management and patient education are cornerstones in managing adrenal insufficiency (AI) to prevent adrenal crisis (AC). Glucocorticoid (GC) education group meetings are increasingly being incorporated into regular healthcare. However, few studies have evaluated its effectiveness.</p><p><strong>Design: </strong>This is a multicentre pre-post intervention study conducted at four university hospitals in Sweden between 2015 and 2019.</p><p><strong>Methods: </strong>A total of 254 patients with AI along with 138 relatives were included. Participants attended a GC education group meeting led by an endocrinologist. Detailed guidance was provided on when and how to adjust GC doses to prevent AC together with instructions and supervised practice of hydrocortisone injections. Questionnaires on self-management were completed by both patients and relatives before the session and again 6 months later. In addition, patients also completed two HRQoL instruments.</p><p><strong>Results: </strong>Patients with AI felt relatively safe and informed about their GC treatment at baseline. However, many lacked adequate knowledge on dose adjustments, including high-risk situations for AC. At follow up, 194 patients (76.4%) and 94 relatives (68.1%) completed the questionnaires. Both patients and relatives showed significant improvements in perceived safety and management of high-risk scenarios for AC. However, some knowledge gaps persisted. The education effort did not result in significant changes in HRQoL.</p><p><strong>Conclusion: </strong>Structured GC education group meetings enhance the knowledge of patients and their relatives to manage AI safely. We consider this a valuable component of AI care.</p><p><strong>Significance: </strong>We highlight the value of repeating sick-day rules and using group education to improve self-management in patients with AI and their relatives.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The application of artificial intelligence in adrenal imaging: current state of knowledge, challenges, and future directions.","authors":"Mateusz Mucha, Zuzanna Roszkowska, Urszula Ambroziak, Małgorzata Bobrowicz, Radosław Roszczyk","doi":"10.1530/EC-26-0267","DOIUrl":"10.1530/EC-26-0267","url":null,"abstract":"<p><strong>Introduction: </strong>Adrenal incidentalomas are common findings on abdominal imaging and require assessment of malignancy risk and hormonal activity. Although most lesions are benign adenomas, differentiating them from pheochromocytomas, adrenocortical carcinomas, metastases, and hormonally active tumors remains challenging, particularly in indeterminate cases. Artificial intelligence (AI) has emerged as a promising tool for improving adrenal lesion detection, segmentation, and characterization.</p><p><strong>Methods: </strong>This narrative review was based on a structured literature search of PubMed, Scopus, and Web of Science for studies published between 2018 and 2025 using the terms 'AI', 'machine learning', 'deep learning', 'radiomics', 'adrenal glands', and 'adrenal imaging'. Priority was given to original studies on segmentation, detection, and lesion characterization. Computed tomography (CT) was the predominant modality, followed by magnetic resonance imaging and positron emission tomography (PET/CT).</p><p><strong>Results: </strong>AI applications in adrenal imaging include gland segmentation, lesion detection, functional assessment, and lesion classification. Recent segmentation models achieved Dice coefficients approaching 0.90. Detection models reported high sensitivity and specificity, although evidence remains limited for small incidentalomas in heterogeneous real-world datasets. In lesion characterization, radiomics- and deep learning-based models showed promising diagnostic performance for differentiating hormonally active adenomas from non-functioning adenomas, lipid-poor adenomas from pheochromocytomas, benign lesions from metastases, and adenomas from adrenocortical carcinoma, with several studies reporting area under the curve (AUC) values above 0.90. Multimodal approaches integrating imaging with clinical data often outperformed imaging-only models.</p><p><strong>Discussion: </strong>Despite encouraging results, most studies were retrospective, single-center studies based on small or selected cohorts, limiting reproducibility and generalizability. Variability in imaging protocols, lack of external validation, and limited workflow integration remain major barriers. Current evidence supports AI mainly as a decision support tool rather than a stand-alone diagnostic system.</p><p><strong>Conclusion: </strong>AI has significant potential to improve adrenal imaging by supporting faster, more accurate, and more reproducible lesion assessment. However, prospective multicenter validation, standardized methodologies, and explainable models are needed before broader clinical implementation.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Later menopause confers no additional protection against osteoporosis in older women.","authors":"Zhiyi Zhou, Hao Li, Zhaojun Lu, Jiarui Chen, Jiang Xue, Siqing Song, Dequan Liu, Yufan Xu, Xinli Zhan, Chong Liu","doi":"10.1530/EC-26-0078","DOIUrl":"10.1530/EC-26-0078","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong></p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic management of adrenal malignancies: adrenocortical carcinoma and pheochromocytoma/paraganglioma.","authors":"Jorge H Hernandez-Felix, Marta Lagana, Deborah Cosentini, Maria Chiara Tacchetti, Alfredo Berruti, Jaydira Del Rivero","doi":"10.1530/EC-26-0334","DOIUrl":"10.1530/EC-26-0334","url":null,"abstract":"<p><p>Adrenal malignancies include adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL), rare endocrine tumors that share an adrenal or extra-adrenal location but differ substantially in origin, hormonal activity, molecular alterations, metastatic potential, and systemic treatment. In ACC, management is guided by stage, resectability, Ki-67, hormone secretion, tumor volume, and pace of progression. Mitotane remains the central ACC-specific therapy, used according to recurrence risk after surgery and as monotherapy in selected patients with advanced, low-volume disease. When rapid tumor control is needed, etoposide, doxorubicin, cisplatin, and mitotane remain the standard first-line regimen. Immune checkpoint inhibitors and multikinase inhibitors have shown activity in some patients, but validated predictive biomarkers are lacking, and access across Europe is limited by reimbursement differences. In later lines, chemotherapy may still be appropriate, including platinum rechallenge in selected cases. PPGL care is increasingly driven by genetics, biochemistry, and functional imaging. Germline testing, biochemical phenotype, and imaging findings are essential for risk assessment and treatment choice. Cyclophosphamide, vincristine, and dacarbazine may be considered for aggressive disease, rapid growth, or high tumor burden. Targeted and radiopharmaceutical approaches have expanded options, including high-specific-activity 131I-iobenguane for MIBG-avid tumors, 177Lu-DOTATATE for somatostatin receptor-positive disease, antiangiogenic tyrosine kinase inhibitors, and HIF-2α inhibition with belzutifan in selected molecular contexts. For both ACC and PPGL, controlling steroid or catecholamine excess is crucial because endocrine complications affect treatment tolerance and outcomes. Future progress requires robust biomarkers, rational treatment sequencing, and trials using disease-specific endpoints beyond radiographic response and integrating patient-centered endocrine, molecular, and overall clinical measures of benefit.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of differences in presentation and postoperative outcomes after adrenalectomy for pheochromocytoma according to age.","authors":"Sukhdeep Jatana, Kevin Verhoeff, Yanbo Wang, Zhicheng Wang, Jiale Zhou, Xiaorong Wu, Yonghui Chen, Maciej Śledziński, Andrzej Hellmann, Marco Raffaelli, Francesco Pennestrì, Mark S Sywak, Alexander Papachristos, Fausto F Palazzo, Tae Yon Sung, Byung-Chang Kim, Yu-Mi Lee, Fiona Eatock, Hannah Anderson, Maurizio Iacobone, Daryl K Gray, Richard C Chaulk, Vasilis Kosmoliaptsis, Nicola Colucci, Harry V M Spiers, Albertas Daukša, Özer Makay, Yiğit Türk, Hafize Basut Atalay, Els J M Nieveen van Dijkum, Anton F Engelsman, Isabelle Holscher, Gabriele Materazzi, Leonardo Rossi, Chiara Becucci, Susannah L Shore, Claire Fung, Alison Waghorn, Radu Mihai, Sabapathy Balasubramanian, Arslan Pannu, Shuichi Tatarano, David Velázquez-Fernández, Julie A Miller, Hazel Serrao-Brown, Yufei Chen, Marco Stefano Demarchi, Reza Djafarrian, Helen Doran, Michael J Stechman, Helen Perry, Johnathan G H Hubbard, Cristina Lamas, Philippa Mercer, Janet MacPherson, Supanut Lumbiganon, María Calatayud, Felicia Alexandra Hanzu, Oscar Vidal, Marta Araujo-Castro, César Minguez Ojeda, Theodosios Papavramidis, Pablo Rodríguez de Vera Gómez, Abdulaziz Aldrees, Tariq Altwjry, Nuria Valdés, Cristina Álvarez-Escola, Iñigo García Sanz, Concepción Blanco Carrera, Laura Manjón-Miguélez, María Paz De Miguel Novoa, Mónica Recasens, Rogelio García-Centeno, Cristina Robles Lázaro, Klaas Van Den Heede, Sam Van Slycke, Theodora Michalopoulou, Sebastian Aspinall, Ross Melvin, Joel Wen Liang Lau, Wei Keat Cheah, Man Hon Tang, Han Boon Oh, John Ayuk, Alessandro Parente, Robert P Sutcliffe","doi":"10.1530/EC-25-0604","DOIUrl":"10.1530/EC-25-0604","url":null,"abstract":"<p><strong>Objective: </strong>Pheochromocytoma is increasingly diagnosed at the extremes of age due to the availability of genetic screening in young patients and incidental detection on imaging in older patients. The aim of this study was to assess the effect of age on presentation and outcomes after adrenalectomy for pheochromocytoma.</p><p><strong>Methods: </strong>A retrospective international multicenter cohort study was performed on patients undergoing adrenalectomy for pheochromocytoma between 2012 and 2022 in 49 centers. Patients were divided into three cohorts: ≤40, 41-59, and ≥60 years old. Univariate and multivariate analyses were used to compare cohorts and assess the impact of age on postoperative outcomes.</p><p><strong>Results: </strong>Of the 2,301 included patients, 551 were ≤40 years (23.9%), 969 were between 41 and 59 years (42.1%), and 781 were ≥60 years (33.9%). Younger cohorts were more likely to have a genetic syndrome (≤40 years 29.4% vs 41-59 years 11.5% vs ≥60 years 6.2%, P < 0.001) and bilateral tumors (10.2 vs 2.3 vs 1.3%, P < 0.001). On multivariable analysis, overall complications seemed less frequent in older cohorts (adjusted odds ratio (aOR): 0.64, P = 0.012, and aOR: 0.66, P = 0.054, for 41-59 and ≥60 years versus ≤40 years), while there were no clear trends in severe complications (Clavien-Dindo grade 3a-5) (aOR: 0.81, P = 0.481, and aOR: 0.78, P = 0.486, respectively) or comprehensive complication index (beta coefficient: -1.49, P = 0.046, and -1.66, P = 0.083, respectively).</p><p><strong>Conclusion: </strong>Age is associated with significant differences in presentation in patients undergoing adrenalectomy for pheochromocytoma, but does not have a clear association with postoperative complications. Pheochromocytoma postoperative morbidity is more likely affected by 'high-risk' disease rather than exclusively by age.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PERSPECTIVE: Beyond the GH-IGF-1 axis: a network perspective integrating clinical observations and mechanistic insights.","authors":"Go Yoshimichi","doi":"10.1530/EC-26-0317","DOIUrl":"10.1530/EC-26-0317","url":null,"abstract":"<p><strong>Background: </strong>Obesity encompasses a heterogeneous group of conditions that include not only simple obesity, but also genetic and endocrine disorders. The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis plays a central role in body composition, insulin sensitivity, and metabolic regulation. We encountered three patients in whom the clinical courses highlighted distinct interactions between obesity and the GH-IGF-1 axis.</p><p><strong>Methods: </strong>We reviewed three representative cases. Case 1 involved acromegaly improved by the peroxisome proliferator-activated receptor-α (PPAR-α) agonist pemafibrate. Case 2 involved Prader-Willi syndrome (PWS) with severe obesity treated using dulaglutide. Case 3 involved severe obesity managed with behavioral therapy. Clinical characteristics and therapeutic responses were analyzed.</p><p><strong>Results: </strong>In case 1, pemafibrate administration resulted in a marked and sustained reduction in IGF-1 levels despite ongoing lanreotide therapy, suggesting a potential hepatic or pituitary interaction between PPAR-α signaling and GH-IGF-1 regulation. In case 2, dulaglutide induced weight loss and reduced insulin requirements in a patient with PWS, a condition characterized by high levels of ghrelin. The therapeutic effect may involve modulation of ghrelin, an upstream regulator of GH secretion. In case 3, a patient with a body mass index of 50.7 kg/m2, behavioral therapy stabilized metabolic deterioration, even though GH and IGF-1 levels remained low after weight reduction, suggesting mechanisms independent of the GH-IGF-1 axis.</p><p><strong>Conclusion: </strong>These findings support a conceptual shift from a linear GH-IGF-1 axis to an integrated GH-IGF-1 network that connects peripheral signals, hypothalamic regulation, and higher brain functions, offering a novel framework for personalized obesity management.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial gene expression-based model for the prediction of thyroid cancer prognosis.","authors":"Weina Zha, Jingwu Li, Yufeng Li, Hanchen Li, Xiaolin Yang, Ying Liu, Chen Wang, Yi Xu, Xingchen Li, Xue Wang, Geling Liu","doi":"10.1530/EC-26-0245","DOIUrl":"10.1530/EC-26-0245","url":null,"abstract":"<p><p>The roles of mitochondrial genes in the development of thyroid cancer (TC) and the associated tumor microenvironment remain to be elucidated. Based on 64 dysregulated mitochondrial genes, unsupervised consensus clustering analysis was performed using TC datasets from The Cancer Genome Atlas and integrated gene expression databases. A dysregulated mitochondrial-based prognostic model was constructed using machine learning. Fourteen prognostic genes were identified, and the correlation between semaphorin 7A (SEMA7A) and immune cell infiltration was validated. The functions of SEMA7A were investigated through plate cloning, scratch wound healing, and Transwell invasion assays. This study constructed a prognostic model for predicting overall survival by identifying 14 mitochondrial dysregulated-based prognostic genes (APOD, ATP2C2, FAM111B, GJB4, GZMA, HHIPL2, IFIT3, IL18, MCEMP1, PRRT4, RGS16, SEMA7A, SLC2A3, and TDRD9). Its effectiveness was validated in an independent cohort. The model accurately predicted OS across cancer stages. SEMA7A expression was significantly upregulated in papillary thyroid carcinoma (PTC) tissues and PTC cell lines. Functional experiments showed that SEMA7A promoted TC progression, including cell proliferation, migration, and invasion. Compared with the SEMA7A low-expression group, the high-expression group showed a larger FOXP3+ regulatory T cell (Treg) population. Although a higher ratio of SEMA7A + CD8-positive cells/SEMA7A + FOXP3-positive cells was observed, increased Treg abundance is known to shift the immune context toward a less cytotoxic and more exhausted state. Thus, oncogenic SEMA7A in TC promotes malignant functions in TC cells and may play an important role in shaping the immunosuppressive microenvironment. Consequently, our mitochondrial dysregulation-based prognostic risk model for TC may offer good clinical application value.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periconceptional use of GLP-1 receptor agonists and the risk of major congenital malformations: a systematic review and meta-analysis.","authors":"Xiangxian Liu, Beijia Xiong, Rui Yang, Haining Wang, Ye Liu","doi":"10.1530/EC-26-0280","DOIUrl":"10.1530/EC-26-0280","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for metabolic diseases, but their reproductive safety remains controversial. We assessed the impact of periconceptional GLP-1RA exposure on birth outcomes to inform their use in reproductive-aged women. PubMed, Embase, Web of Science (through December 2025) were searched for randomized controlled trials (RCTs)/cohorts reporting offspring or pregnancy outcomes in women exposed to GLP-1RAs within three months before conception or during pregnancy. The primary outcome was major congenital malformations (MCMs), compared between neonates with or without maternal GLP-1RA exposure. Secondary outcomes were spontaneous abortion, stillbirth, preterm birth, large for gestational age (LGA), and small for gestational age (SGA). One prospective and five retrospective studies involving 286,599 women (43,577 exposed and 243,022 unexposed to GLP-1RAs) were included. Meta-analysis showed no significant difference in MCM risk in the GLP-1RA exposure group, compared with the non-exposure group (relative risk (RR): 1.02, 95% CI: 0.96-1.08). Risks of preterm birth (RR: 1.09, 95% CI: 0.80-1.49), LGA (RR: 2.31, 95% CI: 0.56-9.44), SGA (RR: 0.71, 95% CI: 0.39-1.27), and stillbirth (RR: 1.16, 95% CI: 0.24-5.69) were not significantly elevated. The incidence of spontaneous abortion was comparable between the two groups in one study. Evidence suggests that periconceptional GLP-1RA exposure in women is not associated with an increased risk of MCMs or other adverse birth outcomes. However, given the observational design and limited exposed pregnancies, these findings should not be interpreted as proof of safety. Large prospective cohorts and RCTs are needed to confirm the safety of GLP-1RA usage before pregnancy.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}