Frontiers in Endocrinology最新文献

{"title":"IVF/ICSI treatment for patients with diminished ovarian reserve with or without Kuntai capsule pretreatment: a retrospective cohort study stratified by a controlled ovarian stimulation regimen.","authors":"Xiaoju Wan, Min Yu, Xingwu Wu, Zhihui Huang, Jun Tan","doi":"10.3389/fendo.2025.1598998","DOIUrl":"10.3389/fendo.2025.1598998","url":null,"abstract":"<p><strong>Background: </strong>Kuntai capsules, a traditional Chinese medicine, are speculated to improve the treatment outcomes of patients with ovarian reserve dysfunction (DOR), but existing evidence is limited.</p><p><strong>Objective: </strong>To investigate the effects of Kuntai capsule pretreatment on the IVF/ICSI treatment outcomes of DOR patients with different ovarian stimulation regimens (PPOS, antagonists, and microstimulation).</p><p><strong>Method: </strong>A retrospective cohort study design was used to include 7271 DOR patients who underwent IVF/ICSI between January 2015 and February 2025. After baseline data were balanced through propensity score matching (PSM), 1474 patients were ultimately included. The number of retrieved eggs, laboratory indicators, and clinical outcomes were compared between the group pretreated with Kuntai capsules and the group not pretreated with Kuntai capsules under three ovarian stimulation regimens, and confounding factors were controlled via a generalized estimating equation (GEE) model.</p><p><strong>Result: </strong>In the PPOS regimen, the number of retrieved eggs (without kuntai: 2.00 [1.00;4.00], with kuntai: 2.00 [1.00;3.00], p<0.001) and normal fertilized eggs (without kuntai:2.00 [1.00;3.00], with kuntai: 2.00 [1.00;2.00], p=0.004) in the Kuntai pretreatment group significantly decreased, but the embryo utilization rate increased (without kuntai:101 (69.2%), with kuntai: 79 (74.5%), p=0.012). There was no difference between the two groups in the antagonist regimen. The Kuntai group had a higher failure rate for egg retrieval in the microstimulation program (without kuntai: 0 (0.00%), with kuntai:6 (6.25%), p=0.029). Among the three regimens, Kuntai pretreatment did not significantly improve the clinical pregnancy rate, live birth rate, or other outcomes (all p>0.05). Age stratification analysis and GEE analysis did not reveal significant differences.</p><p><strong>Conclusion: </strong>Pretreatment with Kuntai capsules did not significantly improve the number of retrieved eggs or clinical pregnancy outcomes in DOR patients under different ovarian stimulation regimens, and its application effect is limited. Further verification through prospective research is needed in the future.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1598998"},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal microcirculation and mechanisms in diabetic kidney disease.","authors":"Xing Hang, Jiang Ma, Yu Wei, Yayun Wang, Xiaoyu Zang, Pengfei Xie, Lili Zhang, Linhua Zhao","doi":"10.3389/fendo.2025.1580608","DOIUrl":"10.3389/fendo.2025.1580608","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD), a severe and long-term complication of diabetes, is a microcirculatory pathology influenced by diabetes-related factors that affects hundreds of millions of people worldwide. DKD is characterized by proteinuria, glomerular injury, and renal fibrosis, ultimately leading to end-stage renal disease. Its pathogenesis is complex and involves multiple cellular and molecular mechanisms. Microcirculatory disorders form the fundamental pathological basis of DKD. These disorders are primarily manifested through changes in the number and structure of renal microvessels, alterations in renal hemodynamics, formation of renal thrombi, glomerular endothelial cell dysfunction, and associated lesions in podocytes and mesangial cells. This article focuses on renal microangiopathy and glomerular endothelial cell (GEC) dysfunction, summarizing the mechanisms associated with microcirculatory lesions in DKD, including nitric oxide (NO), advanced glycation end-products (AGEs), vascular endothelial growth factor (VEGF), the renin-angiotensin-aldosterone system (RAAS), reactive oxygen species (ROS), the NLRP3 inflammasome, protein kinase C (PKC), epidermal growth factor receptor (EGFR), and platelet-derived growth factor (PDGF). Additionally, we briefly introduce the characteristics of DKD animal models in terms of renal microcirculation and discuss the application of relevant technological tools in studying microcirculatory lesions in DKD.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1580608"},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-glucose transporter 2 inhibitors and cardiovascular-kidney-metabolic syndrome: a narrative review.","authors":"Yuqing Wang, Yaqing Wang, Xiaojie He, Xiaodong Li","doi":"10.3389/fendo.2025.1554637","DOIUrl":"10.3389/fendo.2025.1554637","url":null,"abstract":"<p><p>The Cardiovascular-Kidney-Metabolic (CKM) syndrome is a systemic disorder involving obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease, characterized by complex pathophysiological mechanisms that interact and lead to increased morbidity and mortality. In recent years, sodium-glucose transport protein 2 inhibitors (SGLT2i), as a new class of antidiabetic medications, have shown remarkable efficacy in the management of diabetes, renal and cardiovascular diseases. Research has confirmed their ability to reduce cardiovascular events and all-cause mortality. These inhibitors lower blood glucose levels by decreasing renal reabsorption of glucose and sodium, and offer multiple benefits, including lowering blood pressure, reducing body weight, exerting antioxidant, anti-inflammatory, and anti-fibrotic effects, as well as reducing proteinuria and improving glomerular filtration rate. These effects collectively contribute to the improvement of cardiovascular and renal health. Furthermore, SGLT2i have shown potential therapeutic roles at various stages of CKM syndrome, including improving cardiac function, slowing CKD progression, promoting weight loss, and improving lipid profiles. However, the precise mechanisms of action and off-target effects of SGLT2i still require further investigation to evaluate their efficacy and safety under different clinical conditions. Future research directions should include strategies for multiple disease management, combination therapy effects, interdisciplinary collaboration, and long-term follow-up studies to fully understand and optimize the application of SGLT2i in the treatment of CKM syndrome.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1554637"},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of COVID-19 inactivated vaccine on anti-Müllerian hormone in Chinese women: a retrospective cohort study.","authors":"Mingjie Bao, Leizhen Xia, Yan Ling, Quan Wen, Xin Shen, Ting Wang, Si Qian, Liqun Wang, Changhua Wang, Shiwei Peng, Yongping Zhang, Shaoping Zhong, Hongying Xu, Yuan Zhu","doi":"10.3389/fendo.2025.1403722","DOIUrl":"10.3389/fendo.2025.1403722","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess the impact of inactivated COVID-19 vaccine on Anti-Müllerian hormone (AMH) levels in Chinese women.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on women aged 18-45 who had undergone two AMH tests between March 2020 and September 2021. Participants were grouped based on vaccine doses (two- and three-dose), time intervals since vaccination, and manufacturers. The difference in AMH levels and the percentage changes in AMH were measured.</p><p><strong>Results: </strong>The results revealed no significant differences in AMH levels between the vaccinated groups (two- and three-dose) and the control group, both in unadjusted and adjusted analyses. Subgroup analysis showed no statistical difference in either absolute or percentage changes of AMH levels among different time-interval groups and manufacturer groups.</p><p><strong>Discussion: </strong>In conclusion, the number of doses, time interval, and manufacturer of the inactivated COVID-19 vaccine did not affect AMH levels in Chinese women.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1403722"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitor-induced thyroiditis and its potential mechanisms.","authors":"Xueqian Mao, Chaoming Mao, Jiameng Liu, Xi Wang, Yufei Mao","doi":"10.3389/fendo.2025.1584675","DOIUrl":"10.3389/fendo.2025.1584675","url":null,"abstract":"<p><p>The expanding clinical utilization of immune checkpoint inhibitors (ICIs) in oncology has brought increasing attention to thyroid dysfunction as a prominent immune-related adverse event (irAE). Elucidating the pathophysiological mechanisms underlying ICI-induced thyroiditis represents a critical step toward developing evidence-based diagnostic protocols and targeted therapeutic interventions for cancer patients undergoing immunotherapy. This comprehensive review systematically examines current advances in understanding the etiopathogenesis of ICI-induced thyroiditis. First, we described pharmacological characterization of ICIs, then discussed multifactorial analysis of cellular and molecular contributors to thyroid autoimmunity following ICI administration and finally analyzed critical evaluation of emerging hypotheses regarding primary pathogenic drivers. Through this review, we aim to establish mechanistic connections between ICI pharmacodynamics and thyroid tissue immunopathology.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1584675"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rodent models of functional hypothalamic amenorrhea: a systematic scoping review.","authors":"Da-Yeong Min, Song-Yi Kim, Ji-Yeun Park, Minseo Kang, Byoung-Soo Kim","doi":"10.3389/fendo.2025.1456754","DOIUrl":"10.3389/fendo.2025.1456754","url":null,"abstract":"<p><strong>Introduction: </strong>Functional hypothalamic amenorrhea (FHA) is a complex clinical condition crucial to understand and treat due to its intricate etiology, difficulties in applying standard treatments, and significant long-term health effects. This study aimed to summarize and analyze the current research methodologies and findings from rodent models of FHA to provide insights for future investigations.</p><p><strong>Methods: </strong>A literature search was conducted on EMBASE and MEDLINE up to September 23, 2022, using predefined search terms to target FHA-related studies in rodent models. This review focused on experimental studies involving rodent models of FHA, including related nonorganic disorders, such as primary ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). Data were independently collected by researchers, detailing animal models, FHA induction methods, experimental outcomes, and mechanistic exploration, with a synthesis of results comparing FHA with POI and PCOS.</p><p><strong>Results: </strong>Thirty articles (9 on FHA, 14 on POI, and 7 on PCOS) were analyzed, revealing diverse FHA induction methods, including dietary interventions and exercise, inconsistencies in estrous cycle monitoring, and varied focuses in mechanistic investigation. Some studies have emphasized hypothalamic-pituitary-adrenal axis dysfunction, whereas others have investigated ovarian abnormalities. Comparative analyses of POI and PCOS models identified research gaps and suggested future research directions.</p><p><strong>Conclusions: </strong>The incorporation of consistent estrous cycle monitoring and biomarker measurements is crucial for the advancement of FHA research. Future studies should comprehensively investigate hormonal changes and explore potential therapeutic targets for ovarian inflammation and androgen involvement.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1456754"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin improves cardiac function and reduces adverse events in myocardial infarction: a meta-analysis in diabetic and non-diabetic populations.","authors":"Shuang Li, Longlong Wang, Peng Wang, Xiaohui Xu, Yanhua Guo","doi":"10.3389/fendo.2025.1594861","DOIUrl":"10.3389/fendo.2025.1594861","url":null,"abstract":"<p><strong>Background: </strong>Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, frequently driven by acute coronary occlusion resulting from atherosclerosis and arrhythmias. Type 2 diabetes mellitus (T2DM) is a major risk factor for atherosclerotic progression and is associated with worsened cardiovascular outcomes in post-MI patients. Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has emerged as a novel antidiabetic agent with additional cardiovascular benefits. Increasing evidence suggests its potential utility in post-MI care, particularly in patients with coexisting T2DM.</p><p><strong>Objective: </strong>This study aims to systematically evaluate the clinical efficacy of dapagliflozin in improving cardiac function and reducing adverse cardiovascular events in post- MI patients with and without diabetes.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, Web of Science, Cochrane Library, CNKI, and WanFang databases identified relevant clinical studies up to May 22, 2024. Eligible randomized controlled trials (RCTs) and retrospective cohort studies were analyzed using Review Manager 5.3.</p><p><strong>Results: </strong>19 studies (12 RCTs and 7 cohort studies) with 7,128 patients were included. Meta-analysis showed dapagliflozin significantly reduced key cardiac biomarkers and structural parameters, including NT-proBNP (MD = -62.06, 95% CI [-94.59, -29.53], P = 0.0002), LVEDD (MD = -2.58, 95% CI [-3.64, -1.52], P < 0.00001), and LVESD (MD = -2.32, 95% CI [-2.99, -1.66], P < 0.00001), while enhancing LVEF (MD = 3.88, 95% CI [2.24, 5.52], P < 0.00001). It also reduced major adverse cardiovascular events (RR = 0.33, 95% CI [0.18, 0.60], P < 0.05), and heart failure-related rehospitalization (RR = 0.53, 95% CI [0.30, 0.91], P < 0.05). Subgroup analysis revealed consistent cardioprotective benefits in both diabetic and non-diabetic populations.</p><p><strong>Conclusion: </strong>Dapagliflozin significantly enhances cardiac function and reduces adverse cardiovascular events in post-MI patients, independent of diabetes status. These findings support the integration of dapagliflozin into post-MI management strategies. Further large-scale, long-term clinical trials are needed to assess its impact on recurrent MI and long-term survival outcomes.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1594861"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of ovulatory dysfunction and infertility: a scoping review and gene ontology analysis.","authors":"Erin E DiPietro, Sara M Sarasua, Casey S Hopkins, Satishkumar Ranganathan Ganakammal, Luigi Boccuto, Joshua Hurwitz","doi":"10.3389/fendo.2025.1458711","DOIUrl":"10.3389/fendo.2025.1458711","url":null,"abstract":"<p><strong>Background: </strong>The genetic components of the etiologies of ovulatory dysfunction-related infertility (ODRI) are poorly characterized.</p><p><strong>Objectives: </strong>This paper aimed to comprehensively identify, compile, and categorize published research on relationships between genetics and ovulatory-related infertility in humans.</p><p><strong>Methods: </strong>A scoping review was performed on research articles relating human genes, ovulatory dysfunction, and infertility retrieved from PubMed and Web of Science databases. A total of 45 articles were included in the study. The data has been organized into three categories based on relevant findings: polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), and other diagnoses related to ovulatory dysfunction and infertility.</p><p><strong>Results: </strong>Sources revealed 235 different genes linked to ovulatory dysfunction and infertility including follicle-stimulating hormone receptor (<i>FSHR</i>), luteinizing hormone/choriogonadotropin receptor (<i>LHCGR</i>), and bone morphogenic protein 15 (<i>BMP15</i>). PCOS-related articles revealed variants in genes with functions focused on androgen production, such as <i>LHCGR</i> and <i>FSHR</i>. POI-related articles revealed variants in genes with functions focused on folliculogenesis and pubertal development, such as <i>BMP15</i> and <i>STAG3</i>, stromal antigen 3. The \"other\" category revealed genes resulting in enzyme deficiencies interacting with a wide range of functions.</p><p><strong>Conclusions: </strong>In this review, we have highlighted the extreme variability in what is known about the genetics of ODRI by compiling and categorizing genes identified in the literature as associated with ODRI and its associated subtypes. We have also provided a comprehensive list of ODRI genes specifically identified in humans. The findings from this review, specifically the list of ODRI genes, can be used for targeted gene panel development in assisted reproductive technology to improve clinical testing and diagnosis, as well as in developing individualized treatment strategies for ODRI patients.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1458711"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the <i>ENPP1</i> mutation on bone mineralization and ectopic calcification: evidence from <i>in vitro</i> and <i>in vivo</i> models.","authors":"Wanhong Wu, Luna Liu, Yingzhou Shi, Yidan Zhang, Renyuan Qiu, Fang Yan","doi":"10.3389/fendo.2025.1566392","DOIUrl":"10.3389/fendo.2025.1566392","url":null,"abstract":"<p><strong>Background: </strong>Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (<i>ENPP1</i>) plays a key role in mineralization processes, and mutations in this gene are associated with various severe diseases. Clinical case reports have implicated the <i>ENPP1</i> Y451C mutation in diffuse idiopathic skeletal hyperostosis patients, but its precise impact on bone mineralization and ectopic calcification remains unclear.</p><p><strong>Methods: </strong>We used bioinformatics tools and <i>in vitro</i> functional assays to assess the impact of the <i>ENPP1</i> Y451C mutation on protein structure and enzymatic activity. Furthermore, we generated a knock-in mouse model (<i>Enpp1^Y433C</i> ) to evaluate microarchitecture or signs of ectopic calcification by Micro-CT.</p><p><strong>Results: </strong>Bioinformatics analysis and <i>in vitro</i> assays showed that the Y451C mutation affects the <i>ENPP1</i> protein's structure, reducing enzymatic activity by approximately 50%. We successfully generated the <i>Enpp1^Y433C</i> knock-in mouse model. However, no significant differences were observed in body phenotype or biochemical markers in <i>Enpp1^Y433C</i> mice at 3, 5, and 10 months, compared to wild-type controls. Similarly, no significant changes were observed in bone microarchitecture or signs of ectopic calcification.</p><p><strong>Conclusion: </strong>The <i>ENPP1</i> Y451C mutation significantly reduces enzymatic activity <i>in vitro</i>, yet the <i>Enpp1^Y433C</i> knock-in mouse model shows no significant abnormalities in mineralization, providing additional evidence for the pathogenicity assessment of <i>ENPP1</i> Y451C variant. Given that these results are from mouse models, further studies are required to clarify its pathogenicity in humans.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1566392"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced sensitivity to thyroid hormones is associated with differentiated thyroid cancer in the euthyroid thyroidectomy population.","authors":"Huaijin Xu, Hongzhou Liu, Xiaodong Hu, Xiaomeng Jia, Zhe Xue, Anning Wang, Shaoyang Kang, Zhaohui Lyu","doi":"10.3389/fendo.2025.1595002","DOIUrl":"10.3389/fendo.2025.1595002","url":null,"abstract":"<p><strong>Background: </strong>The inconclusive associations between thyroid-related hormones and differentiated thyroid cancer (DTC) suggest complex pathophysiologic processes, for which thyroid hormone sensitivity may provide new insights.</p><p><strong>Methods: </strong>We retrospectively analyzed preoperative clinical data and postoperative pathological data of 9,515 euthyroid adults who underwent thyroidectomy for thyroid nodules pathologically confirmed as benign nodules or DTC. Composite thyroid parameters were calculated, including TSH index (TSHI), thyrotroph thyroxine resistance index (TT4RI), FT3/FT4 ratio (FT3/FT4) and the thyroid's secretory capacity (SPINA-GT).</p><p><strong>Results: </strong>Increased TSHI (OR=1.34, 95%CI: 1.27-1.41) and TT4RI (OR=1.35, 95%CI: 1.28-1.42) reflecting reduced central thyroid hormone sensitivity, decreased FT3/FT4 (OR=0.81, 95%CI: 0.77-0.86) reflecting reduced peripheral thyroid hormone sensitivity, and decreased SPINA-GT (OR=0.78, 95%CI: 0.74-0.82) were associated with DTC after adjustment for confounders. The contributions of thyroid hormone sensitivity indices remained in subgroups stratified by age, sex, metabolic factors, thyroid autoimmunity status, and nodule size. A non-linear relationship between thyroid hormone sensitivity indices and probability of DTC was observed. The association of DTC with TT4RI or TSHI was stronger than with other thyroid parameters such as TSH (thyroid stimulating hormone). ROC analysis for the distinction between DTC and benign disease showed no single thyroid parameter with the coexistence of high sensitivity and specificity.</p><p><strong>Conclusion: </strong>Reduced central and peripheral sensitivity to thyroid hormones is associated with DTC in the euthyroid thyroidectomy population and provides additional information on the odds of malignancy in thyroid nodules at risk for surgery, warranting consideration of the role of sensitivity to thyroid hormones in mechanisms and prediction models for DTC.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1595002"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}