Endocrine Connections最新文献

{"title":"Prevalence and risk factors of eligibility for anti-osteoporosis medication in a cohort of men ≥50 years and postmenopausal women who had already experienced bariatric surgery.","authors":"Thomas Flament, Hélène Verkindt, Léa Mortain, François Pattou, Julien Paccou","doi":"10.1530/EC-25-0368","DOIUrl":"10.1530/EC-25-0368","url":null,"abstract":"<p><p>The 2022 recommendations of the European Calcified Tissue Society (ECTS) suggest initiating anti-osteoporotic medication (AOM) in case of a T-score ≤ -2 and/or in case of a fragility fracture within less than 2 years. Therefore, this study aimed to evaluate the eligibility for AOM in a cohort of patients referred for bone health assessment after bariatric surgery. This observational, cross-sectional, and monocentric study conducted at Lille University Hospital evaluated the prevalence of AOM eligibility according to the ECTS criteria in postmenopausal women and men aged ≥50 years referred for bone health assessment after bariatric surgery, either Roux-en-Y gastric bypass or sleeve gastrectomy, at least 2 years after bariatric surgery. Between June 2019 and June 2023, all participants were referred for bone health assessment, including systematic screening using dual-energy X-ray (DXA) and a standardized questionnaire by a radiology technician. Data between June 2023 and May 2024 were retrospectively reviewed. Among 140 patients (120 women, with an average age of 59 (55-63) years) seen for bone health assessment between June 2019 and June 2023, 33 met the ECTS guidelines for AOM, indicating a prevalence of 24% (CI 95%: 17-31%). Most patients met the BMD T-score ≤ -2 criterion (n = 26/140, 19% (CI 95%: 12-25%)) and/or had a recent fragility fracture history (n = 14/140, 10% (CI 95%: 5-15%)). In this study, one-fourth of the participants were eligible for AOM according to the ECTS guidelines.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing transition care for adolescents and young adults with adrenal insufficiency in the Netherlands: a holistic model for improved patient outcomes.","authors":"H L Claahsen-van der Grinten, K Davidse, K M A Dreijerink, J P van Eck, N Reisch, S Lajic, E Foltête, N Stikkelbroeck, H Vlaardingerbroek","doi":"10.1530/EC-25-0324","DOIUrl":"10.1530/EC-25-0324","url":null,"abstract":"<p><p>Transition from paediatric to adult healthcare presents unique challenges for adolescents with chronic conditions such as adrenal insufficiency (AI). This process requires careful coordination to ensure continuity of care and support as young patients adapt to managing their condition independently. In the Netherlands, transition care follows a structured, quality-driven approach aimed at meeting the medical, psychological, and social needs of adolescents with chronic conditions. This paper will define key transition-related terms, explain the framework's five core pillars, explore best practices for transition, and discuss quality indicators and an implementation plan to facilitate effective transition care for AI patients.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation and implementation of the Dutch PHPQoL for primary hyperparathyroidism.","authors":"Jaimie L H Zhang, Abbey Schepers, Jaap F Hamming, Lano Osman, Susan M Webb, Lieke Welling, Elizabeth M Winter, Marieke Snel, Natasha M Appelman-Dijkstra","doi":"10.1530/EC-25-0400","DOIUrl":"10.1530/EC-25-0400","url":null,"abstract":"<p><strong>Background: </strong>Patients with primary hyperparathyroidism (PHPT) often present with nonspecific neuropsychological symptoms, which remain challenging to quantify. While parathyroidectomy (PTx) recently has been recommended for asymptomatic patients, its benefit remains unclear as existing evidence relies on generic health-related quality of life (HRQoL) tools. In contrast, the disease-specific PHPQoL questionnaire offers more sensitive and clinically relevant symptom assessment. This study aims to translate and validate the PHPQoL for Dutch use and to evaluate the effect of PTx on HRQoL in both symptomatic and asymptomatic PHPT patients.</p><p><strong>Methods: </strong>In this single-center prospective study, PHPT patients with at least one surgical indication underwent either PTx or conservative treatment based on medical requirement and patient preference. Clinicians classified patients as asymptomatic if no hypercalcemia-related complaints were present. HRQoL questionnaires were assessed using the PHPQoL, SF-36, and EQ-5D questionnaires at inclusion and 3 months after treatment. Statistical significance was set at P < 0.001.</p><p><strong>Results: </strong>Of the 100 patients included (mean age: 61.5 ± 12.4 years, 77% female), 89 underwent PTx (symptomatic: n = 47, asymptomatic: n = 42), and 11 received conservative treatment. The PHPQoL demonstrated strong psychometric properties and correlated well with generic HRQoL questionnaires. Following PTx, mean PHPQoL scores improved from 52.2 to 65.9 (P < 0.001); in asymptomatic patients, scores rose from 58.3 to 71.7 (P < 0.001).</p><p><strong>Conclusion: </strong>The Dutch version of the PHPQoL is a valid and reliable tool for assessing PHPT and demonstrates significant HRQoL improvements following PTx, including in asymptomatic patients, which may be underestimated by generic instruments.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared molecular mechanisms between type 2 diabetes and thyroid cancer: integrated bioinformatics insights for prognostic biomarker discovery.","authors":"Jiahui Qi, Chuanzhi Chen, Feng Zhu, Chuankai Chen, Yue Wang","doi":"10.1530/EC-25-0181","DOIUrl":"10.1530/EC-25-0181","url":null,"abstract":"<p><strong>Background: </strong>Thyroid cancer (TC) is a prevalent endocrine malignancy with rising global incidence, particularly among women. Emerging evidence suggests a significant association between type 2 diabetes mellitus (T2D) and TC, potentially mediated by hyperinsulinemia, insulin resistance, and chronic inflammation. However, the molecular mechanisms linking these diseases remain poorly understood.</p><p><strong>Methods: </strong>We integrated transcriptomic datasets from the Gene Expression Omnibus (GEO) database (GSE33630, GSE35570, GSE60542 for TC; GSE86468 for T2D) to identify shared differentially expressed genes (DEGs). Functional enrichment, protein-protein interaction networks, and Cox regression analyses were employed to elucidate pathways and prognostic biomarkers.</p><p><strong>Results: </strong>We identified 28 shared DEGs between TC and T2D, with CD44, TGFBI, RUNX2, and GJA1 as key hub genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted pathways involving cell adhesion, extracellular matrix remodeling, and NF-κB signaling. A risk model incorporating seven genes (e.g., PRDM1 [protective] and ZFPM2 [risk]) stratified TC patients into high- and low-risk groups with distinct survival outcomes (P = 0.017).</p><p><strong>Conclusion: </strong>T2D and TC exhibit overlapping genetic dysregulation, particularly in pathways governing metabolic reprogramming and tumor microenvironment crosstalk. Notably, PRDM1 and ZFPM2 may serve as therapeutic targets for TC in patients with concurrent diabetes.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Succinate dehydrogenase-related pheochromocytoma and paraganglioma (SDHx-PPGL): clinical and genetic insights from an Indian study.","authors":"Ketki Sunil Ambulkar, Anima Sharma, Vijaya Sarathi, Saba Samad Memon, Anurag Ranjan Lila, Rohit Barnabas, Manjiri Karlekar, Virendra Patil, Samiksha Hegisthe, Gwendolyn Fernandes, Sameer Rege, Gaurav Malhotra, Hemangini Thakkar, Nalini S Shah, Tushar R Bandgar","doi":"10.1530/EC-25-0500","DOIUrl":"10.1530/EC-25-0500","url":null,"abstract":"<p><strong>Objective: </strong>Data on succinate dehydrogenase-related pheochromocytoma and paraganglioma (SDHx PPGL) in India are limited. We describe the clinical and genetic characteristics of SDHx PPGL from a single center in western India.</p><p><strong>Design, patients, and measurements: </strong>A retrospective review of SDHx PPGL patients was performed for clinical, imaging, genetic, and treatment details.</p><p><strong>Results: </strong>Among 46 patients (39 probands, 24 males), the median age at diagnosis was 32.5 (IQR: 23-41) years. We report the youngest patient with SDHC (age 8 years). SDHB mutations were the most prevalent (24/39 probands), followed by SDHD, SDHC, SDHA, and SDHAF2. We report the first Indian family with the SDHAF2 c.232G>A mutation (paternal inheritance) and the index patient with metastasis. Paraganglioma (PGL) (single or multiple) was common (80%), followed by pheochromocytoma (11%) and multifocal PPGL (9%). sPGL predominated in the SDHB cohort (80.6%), whereas multiple/multifocal PPGLs were common in others. Biochemically silent tumors were noted in 26% patients. 68Ga-DOTATATE PET/CT was the most sensitive imaging modality. The prevalence of metastasis was high in patients with SDHB variants (51.7%) but was also substantial in those with other SDHx genes (29.4%). Most probands harbored unique variants, and we report ten novel SDHx gene mutations. Surgical treatment was performed in 67.3% cases, and systemic radiotherapy was utilized in advanced cases, achieving stable disease in most cases.</p><p><strong>Conclusion: </strong>In this largest Indian cohort of SDHx PPGL, a high metastatic burden, SDHB dominance, and novel gene variants were noted.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trend in body mass index during childhood in 460 girls with idiopathic central precocious puberty.","authors":"Alfredo Vicinanza, Obsse Oli Atomssa, Andrea Nebbioso, Fiorenza Ulgiati, Sophie Lambert, Sylvie Tenoutasse, Emese Boros, Claudine Heinrichs, Cécile Brachet","doi":"10.1530/EC-25-0215","DOIUrl":"10.1530/EC-25-0215","url":null,"abstract":"<p><strong>Objective: </strong>A secular trend toward earlier puberty onset in girls has been widely documented, with childhood overweight proposed as a contributing risk factor. This study aims to characterize body mass index (BMI) standard deviation score (SDS) trajectories over the 6 years preceding idiopathic central precocious puberty (CPP) onset in girls.</p><p><strong>Design and methods: </strong>This retrospective, single-center study included 460 girls diagnosed with idiopathic CPP at the Academic Children's Hospital Queen Fabiola between 2002 and 2022. The cohort was stratified into sporadic CPP, familial CPP, and CPP in internationally adopted girls. Clinical and demographic data were collected, and BMI trajectories were analyzed using piecewise mixed linear models. Pubertal onset (T0) was defined as Tanner stage B2.</p><p><strong>Results: </strong>Among the 460 cases, 285 (62%) were sporadic, 145 (31.5%) familial, and 30 (6.5%) adoption-related CPP. In addition, 11.7% were born small for gestational age (SGA). BMI SDS increased significantly during the 6 years preceding T0 across the entire cohort. The steepest rise occurred between 6 and 3 years before T0 (+0.21 SDS/year (95% CI: 0.13-0.29)), followed by a slower increase in the 3 years before T0 (+0.15 SDS/year (95% CI: 0.11-0.19)), and a subsequent stabilization post-T0 (+0.06 SDS/year (95% CI: -0.01-0.14)). The BMI increase rate was similar across all subgroups.</p><p><strong>Conclusions: </strong>Girls with idiopathic CPP show a significant prepubertal BMI SDS increase, with similar trajectories in sporadic and familial cases. The overrepresentation of SGA-born and adopted girls suggests that genetic and environmental factors may contribute to early pubertal onset.</p><p><strong>Plain language summary: </strong>This study is the first to track BMI trajectories up to 6 years before idiopathic CPP onset in girls, revealing an early rise in BMI SDS across all subgroups (sporadic, familial, and adopted girls). Notably, SGA-born and adopted girls showed similar BMI patterns but were overrepresented in this CPP cohort.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Gender Incongruence module in the European Registries for Rare Endocrine & Bone Conditions (EuRREB): first results, current insights and future directions.","authors":"Silvia Ciancia, Mariya Cherenko, Daniel Klink, Kanetee Busiah, Aneta Gawlik-Starzyk, Wiktoria Kempinska, Hedi L Claahsen-van der Grinten, S Faisal Ahmed, Sabine E Hannema, Martine Cools","doi":"10.1530/EC-25-0401","DOIUrl":"https://doi.org/10.1530/EC-25-0401","url":null,"abstract":"<p><strong>Objective: </strong>Healthcare for transgender and gender diverse (TGD) adolescents varies across countries, therefore a specific module dedicated to gender incongruence (GI) within the European Registries for Rare Endocrine & Bone Conditions (EuRREB) was developed to understand this variation. Additionally, this project aims to facilitate longitudinal data collection through international, multicenter collaborations with the ultimate scope of refining current guidelines.</p><p><strong>Methods: </strong>The module consists of five sections covering general information, including the presence of mental health comorbidities, and specific information on gonadal hormone suppression (GHS), gender-affirming hormone (GAH) therapy, fertility preservation, gender-affirming surgery (GAS), and eventual stop of treatments.</p><p><strong>Results: </strong>As of December 2024, five centers from four European countries (Belgium, Poland, Switzerland, and the Netherlands) had started to report cases in the registry. Preliminary findings highlight the existence of some differences among centers, often consequence of differences in national regulations and healthcare policies, e.g. reimbursement criteria. Importantly, mental health comorbidities were commonly reported among TGD adolescents from all centers, emphasizing the need for comprehensive psychological assessment and targeted psychological care. While currently still at an early stage, this longitudinal data collection will offer insights in important long-term outcomes such as uptake of surgical or reproductive options, or detransition, in large cohorts.</p><p><strong>Conclusion: </strong>The data collected so far highlight the importance of wide multicenter data collection in advancing knowledge on the care of TGD adolescents. Expanding this registry and fostering international collaboration will be crucial in standardizing protocols, improving care, and guiding evidence-based recommendations for TGD youth.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Heterogeneity and Imaging-driven Genetic Screening Priorities in Patients with Radiologically Suspected Primary Bilateral Macronodular Adrenal Hyperplasia.","authors":"Huaijin Xu, Bing Li, Kang Chen, Huixin Zhou, Wangtian Ma, Yajing Wang, Yaqi Yin, Weijun Gu, Yiming Mu, Zhaohui Lyu","doi":"10.1530/EC-25-0290","DOIUrl":"https://doi.org/10.1530/EC-25-0290","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical spectrum, ARMC5 mutation distribution, and metabolic/cardiovascular risks in patients with radiologically suspected primary bilateral macronodular adrenal hyperplasia (PBMAH).</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Methods: </strong>We analyzed clinical characteristics and germline ARMC5 mutations in patients meeting radiologic criteria for PBMAH (bilateral adrenal nodules ≥1 cm), excluding non-adrenocortical lesions or bilateral adenomas with adrenal atrophy.</p><p><strong>Results: </strong>The subgroup distribution among 485 patients with radiologically suspected PBMAH was as follows: nonfunctional adrenal tumors (NFAT, 30.1%), mild autonomous cortisol secretion (MACS, 41%), overt Cushing's syndrome (CS, 14.4%), primary aldosteronism (PA, 8.9%), and coexisting PA and MACS (PA+MACS, 5.6%). Imaging revealed a higher proportion of multiple confluent adrenal nodules in the MACS and CS groups compared to others (P<0.05). Cortisol-related comorbidities (hypertension, diabetes, etc.) showed no statistically significant differences between MACS and NFAT. Germline ARMC5 testing in 62 unrelated patients identified 7 novel pathogenic variants. Pathogenic mutations were detected only in MACS and CS groups, with no significant difference observed between them (P>0.05). Multiple confluent nodules were present in all ARMC5-mutated patients (16/16) but in fewer ARMC5 wild-type patients (20/44), with high sensitivity and negative predictive value for the prediction of germline pathogenic mutations.</p><p><strong>Conclusion: </strong>No significant cortisol-related comorbidity differences were observed between radiologically suspected PBMAH patients with NFAT and MACS. Germline ARMC5 screening should prioritize patients with radiological findings of multiple confluent macronodules.</p><p><strong>Significance statement: </strong>Our work provides new insights into the management of primary bilateral macronodular adrenal hyperplasia (PBMAH): 1) MACS and NFAT patients with radiologically suspected PBMAH (i.e., bilateral benign adrenal macronodules) may require equal clinical attention; 2) We identified 7 novel ARMC5 pathogenic variants; 3) Multiple confluent adrenal nodules on imaging demonstrate predictive value for ARMC5 pathogenic mutations, refining genetic screening criteria.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"tsRNA-25172 inhibits aldosterone secretion in aldosterone-producing adenomas.","authors":"Qiwei Fan, Liqing Liu, Zhihua Jiang, Shanshan Feng, Jiancheng Wang, Jianrong Chen","doi":"10.1530/EC-25-0210","DOIUrl":"10.1530/EC-25-0210","url":null,"abstract":"<p><p>The pathophysiology of aldosterone-producing adenomas (APAs) is characterized by aldosterone hypersecretion. Transfer RNA-derived small RNAs (tsRNAs) are novel non-coding RNAs, which are involved in multiple biological processes. However, the role of tsRNAs in aldosterone synthesis and APAs remains poorly understood. Herein, immunohistochemistry was employed to assess the expression levels of aldosterone synthase CYP11B2 in APA patients. The differentially expressed miRNAs, piRNAs, and tsRNAs between adrenocortical adenomas (ACAs) and normal tissues were identified using small RNA sequencing data. The regulatory role of tsRNA-25172 on aldosterone synthesis in NCI-H295R cells was evaluated by qRT-PCR, CCK-8, and ELISA. We observed an abnormal increase in CYP11B2 expression in APA tissues. A total of 18 differentially expressed miRNAs, 5 differentially expressed piRNAs, and 159 differentially expressed tsRNAs were identified between ACA and normal tissues. Enrichment analysis revealed that dysregulated small RNAs were predominantly associated with cell adhesion, intracellular signal transduction, calcium signaling, and Wnt signaling pathways, leading to the identification of an ER-related gene, TGM2. tsRNA-25172 and tsRNA-25173 were downregulated in the ACA group. tsRNA-25172 mimics significantly inhibited the levels of aldosterone and cortisol in NCI-H295R cells. In contrast, tsRNA-25173 did not exhibit a notable effect. Moreover, overexpressed tsRNA-25172 markedly inhibited CYP11B2 and its target gene TGM2. Our findings reveal a pivotal role for tsRNA in APAs, potentially offering a novel exploratory approach and therapeutic target for the pathogenesis of APAs.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074593","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":"DNA Methylation in Kallmann Syndrome: Impacts on Neuronal Development and Spermatogenesis.","authors":"Rongrong Wang, Xiaogang Li, Jingdi Zhang, Xi Wang, Jiangfeng Mao, Xinxin Feng, Siyu Wang, Yongzhe Li, Xueyan Wu, Ye Guo","doi":"10.1530/EC-25-0224","DOIUrl":"10.1530/EC-25-0224","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to comprehensively characterize the DNA methylation profile in the sperm of patients with Kallmann Syndrome (KS), providing new insights into the potential epigenetic mechanisms contributing to the pathogenesis of the disease.</p><p><strong>Methods: </strong>Sperm samples from patients with KS and Healthy Controls (HCs) were analyzed for DNA methylation patterns. Differentially methylated regions (DMRs) were identified, and the associated genes underwent enrichment analysis. Spermatogenesis-related genes were screened, analyzed for functional enrichment, and key genes were identified using the STRING database and CytoHubba. Their correlations with semen parameters were then evaluated.</p><p><strong>Results: </strong>This study analyzed six patients with KS and six age-matched HCs, revealing higher DNA methylation in patients with KS. 4,749 DMRs were identified (4,020 hypermethylated, 729 hypomethylated), affecting genes linked to neuronal function, migration, and gonadotropin-releasing hormone (GnRH) secretion. DMRs were also observed in key KS-related genes, including CHD7, DCC, IL17RD, NELFA, and SEMA3E. Moreover, 1,938 spermatogenesis-related genes were identified within the gene body, with significant enrichment in chromosome remodeling pathways. Notably, core spermatogenesis genes such as BRCA1, H3FC3 and HSP90AA1 exhibited significant correlations with semen parameters.</p><p><strong>Conclusion: </strong>This study identified DNA methylation changes in patients with KS after gonadotropin or pulsatile GnRH therapy, reflecting downstream epigenetic consequences of congenital gonadotropin deficiency and its treatment. These alterations are associated with persistent spermatogenic abnormalities, providing a foundation for future studies on epigenetic biomarkers and potential interventions.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}