Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy. Venous thromboembolic events (VTE) have been reported in ACC patients. ACC is often associated with endogenous hypercortisolism, which is linked to increased VTE risk. The primary objective of this retrospective study in patients who received treatment for ACC at Amsterdam UMC between 2003 and 2024 was to determine the total incidence of VTE. Secondary objectives included determining the incidence of VTE after adrenalectomy and identifying risk factors for VTE. Patients were categorised into VTE and non-VTE groups. Mann-Whitney U tests, unpaired t-tests, and Chi-square or Fisher's exact tests were used in order to assess differences. Seventy-four patients were included, of whom ten (13.5%) had experienced a VTE during the observation period, amounting to 29 VTEs (CI 13-58) per 1,000 patient-years. All VTEs were pulmonary embolisms. Sixty-four patients underwent adrenalectomy. Fifty (98%) patients, for whom data were available, used peri-operative thromboprophylaxis or anticoagulant therapy. The median duration of peri-operative thromboprophylaxis was 5 days (IQR 4-11, range 0-90). Two patients experienced a VTE within 6 months after surgery (3.3%). Four patients with a VTE (40%) had cortisol-producing ACC (P = 0.83). We conclude that the overall incidence of VTE in ACC patients is high. The incidence of post-operative VTE after adrenalectomy for ACC was lower in this cohort compared with that reported in the literature. No risk factors for VTE were identified; most notably, hypercortisolism was not associated with increased VTE incidence. Our findings expand the literature addressing this issue and reaffirm the importance of the use of peri-operative thromboprophylaxis in ACC patients undergoing adrenalectomy.
Abstract: Klinefelter syndrome (KS) is an underdiagnosed condition, affecting approximately 1 in 600 male births. Despite its relatively high prevalence, more than two-thirds of affected individuals remain undiagnosed, and clinical awareness is limited. KS presents with a highly variable phenotype, requiring lifelong, multidisciplinary care that spans pediatric and adult specialties. However, care is often fragmented, and there is no standardized approach to transitioning individuals from pediatric to adult healthcare services. Structured, longitudinal data collection is essential to better understand KS across the lifespan and to facilitate the transition process. To address this need, a group of clinical experts (pediatric and adult specialists) and patient representatives developed structured, age-adapted modules for longitudinal clinical data collection in KS. Through an iterative consensus process, a list of clinical, biochemical, diagnostic, and therapeutic parameters was developed. Experts then systematically evaluated and prioritized these parameters based on clinical relevance and feasibility of collection in routine practice. The final modules are designed to guide standardized assessments across four key age groups: infancy, childhood, adolescence, and adulthood. The structured templates aim to support healthcare professionals in providing comprehensive, age-appropriate care while enabling systematic data collection for research. These modules provide a framework for tracking key clinical parameters during the transition from pediatric to adult care, ensuring continuity and optimizing long-term health outcomes for individuals with KS. Implementation of these modules in clinical registries will facilitate pooled analyses, helping to address unresolved clinical questions and improve care across the lifespan.
Plain language summary: Understanding and improving care for people with Klinefelter syndrome: Klinefelter syndrome (KS) affects approximately 1 in 600 males but often remains undiagnosed. To improve lifelong care, experts developed structured data collection tools for different age groups. This approach enhances clinical care, supports research, and facilitates smoother transitions from pediatric to adult healthcare.
Objective: Renin measurement is a key to diagnosing primary aldosteronism (PA). However, it remains unclear whether plasma renin activity (PRA) or direct renin concentration (DRC), which are based on different principles, offer superior performance. This study aimed to compare their diagnostic potential in PA.
Methods: This cross-sectional observational study was conducted at a single institution, and enrolled consecutive patients hospitalised for PA diagnosis. PRA and DRC were measured for the same samples during the captopril challenge, saline infusion, and furosemide upright tests. We evaluated renin responsiveness, defined as renin changes from baseline in each test, and the relationship between PRA and DRC.
Results: Seventy-two patients were classified into PA and non-PA groups. The patients in the PA group were further classified into unilateral and bilateral PA groups using adrenal vein sampling. The renin responsiveness positivity was significantly higher for DRC than for PRA in the PA group across all tests. The DRC/PRA ratio did not differ significantly between PA and non-PA groups, while the DRC/PRA ratio was significantly lower in the unilateral PA group than in the bilateral PA group. The correlation between PRA and DRC was weak in the PA group, especially in the low-renin range.
Conclusions: Renin changes were more consistently detected with DRC than with PRA in the low-renin range. The DRC/PRA ratio was lower in unilateral PA than in bilateral PA, suggesting potential utility for recognising unilateral PA, although this finding should be considered exploratory.
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.
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.
Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
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