Endocrine Connections最新文献

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.

Objective: 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.

Design, patients, and measurements: A retrospective review of SDHx PPGL patients was performed for clinical, imaging, genetic, and treatment details.

Results: 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.

Conclusion: In this largest Indian cohort of SDHx PPGL, a high metastatic burden, SDHB dominance, and novel gene variants were noted.

Objective: 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.

Design and methods: 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.

Results: 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.

Conclusions: 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.

Plain language summary: 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.

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.