Endocrine Connections最新文献

Background: Gender identity (GI) is the unified and persistent self-perception on the male-female spectrum, and its acquisition is a multifactorial process. GI is generally consolidated around ages 3-4 years. The gender identity questionnaire for children (GIQC) aims to assess GI in both clinical and non-clinical populations. The aim of the research is to evaluate GI in relation to social and biological factors.

Methods: Single-center, prospective birth-cohort study enrolling those born at term, appropriate for gestational age. The GIQC was administered to the parents at age 3. The scoring was performed through the original coding scheme and the new coding scheme for the non-clinical group based on three scales: female typical behavior (FTB), male typical behavior (MTB), and cross-gender (CG). Anthropometrics, anogenital distances, and urinary hormone assessment were performed at birth, 3, 6 and 36 months.

Results: 86 children (males 53) participated. FTB, MTB, and CG scores differed significantly according to sex: boys (3.28 ± 0.59) scored higher than girls (2.45 ± 0.44) on MTB, while girls (3.41 ± 0.75) scored higher than boys (1.92 ± 0.61) on FTB. Girls (4.14 ± 0.64) scored higher than boys (3.66 ± 0.88) on the CG scale. Within the whole sample, the FTB scale showed a moderate negative correlation with MTB (r: -0.464, P < 0.01) and a positive one with CG (r: 0.377, P < 0.001) in the female population. Correlations exist between MTB and ano-scrotal distance (AGD-AS) in males, and between MTB and ano-clitoral distance (AGD-AC) in females.

Conclusion: Our findings confirm that by age 3, most children express differentiated sex-typed behavior according to the sex assigned at birth. In addition, androgenization appears to play a role in GI development in males.

Introduction: The transition from pediatric to adult care in individuals with type 1 diabetes (T1D) often presents significant challenges, including disruptions in follow-up continuity and metabolic control.

Objective: The aim of this study is to assess healthcare utilization, follow-up continuity, metabolic control (HbA1c levels), and the development of complications after transition to adult care within a transition clinic setting.

Methods: A retrospective analysis was performed on 118 individuals with T1D who transitioned to adult care. Demographic data, along with pre- and post-transition HbA1c levels, chronic complications, treatment modifications, and follow-up attendance, were collected and analyzed.

Results: Of the 118 participants, 67% (n = 80) transitioned through the transition council, with 62.5% (n = 50) maintaining regular follow-up in adult care. However, 27.5% (n = 30) experienced follow-up discontinuity. The mean HbA1c in the last year of pediatric care was 7.95 ± 1.27%, which slightly decreased to 7.73 ± 1.17% in the first year of adult care and remained stable at 7.74 ± 1.17% in the second year. Complication rates increased from 18% pre-transition to 26% during adult follow-up.

Conclusion: Despite the challenges faced during the transition, transition clinics play a crucial role in supporting follow-up continuity and improving metabolic control. Multidisciplinary care and individualized treatment modifications are essential in reducing complication risks. Future research should include larger sample sizes to better address long-term health outcomes and optimize the transition process.

Steroid receptor coactivators (SRCs) are master regulators of nuclear receptor signaling and play essential roles in female reproductive physiology. By integrating steroid hormone signaling with growth factors and metabolic pathways, SRC-1, SRC-2, and SRC-3 coordinate key processes such as decidualization, placental development, and ovarian function. Dysregulation of SRCs is strongly linked to the progression of benign gynecologic disorders, including polycystic ovary syndrome (PCOS), endometriosis, and uterine fibroids, largely through enhancing hormonal hypersensitivity and disrupting nuclear receptor-mediated cellular pathways. Emerging evidence further implicates specific SRC isoforms in disease pathogenesis, underscoring their potential as biomarkers and therapeutic targets. To inhibit SRC activity, natural compounds (e.g., gossypol, bufalin, verrucarin A) and synthetic small molecules (e.g., SI-2, SI-12, MCB-613) have been developed, demonstrating preclinical efficacy across several human diseases. However, their application in benign reproductive disorders remains largely unexplored. This review summarizes current knowledge of SRC biology in benign gynecologic disorders, outlines their mechanistic roles in disease progression, and highlights opportunities for clinical translation. Targeting SRCs may ultimately represent a novel, nonhormonal, fertility-preserving therapeutic strategy in women's health.

Background: Primary spontaneous osteonecrosis of the knee (SONK) is a debilitating condition that primarily affects elderly patients with an unknown etiology. Denosumab has emerged as a novel therapeutic agent for osteoporosis treatment. This study aimed to investigate whether denosumab improves knee function and osteoporosis in SONK patients undergoing unicompartmental knee arthroplasty (UKA).

Methods: Between January 1, 2018, and December 31, 2022, patients with knee osteonecrosis undergoing UKA were enrolled. Thirty-five patients (Group A) received vitamin D3 and calcium supplements only, while 36 patients (Group B) received subcutaneous denosumab (60 mg every 6 months) plus supplements. Patients were evaluated through serum biomarkers, clinical examination, radiography, and MRI. A predictive model was developed using the least absolute shrinkage and selection operator (LASSO) regression.

Results: The mean follow-up was 2.11 ± 0.99 years. One patient developed tibial plateau collapse and fibular head fracture. At 24 months, Group B showed significantly better HSS scores (T = 15.07, P = 0.04), VAS scores (T = 1.11, P = 0.04), and ROM (T = 15.07, P = 0.02) compared to Group A. Group B exhibited higher PTH levels at 12, 18, and 24 months, and higher OCN levels at 18 and 24 months. At 24 months, Group B had lower CTX but higher T-scores and BMD. Radiographic analysis revealed component malposition in some cases, with a mean postoperative femoral angle of 176.1° ± 2.3°. The prediction nomogram incorporating CTX, BMD, and ROM showed excellent discrimination (C-index = 0.925, 95% CI: 0.881-0.969), confirmed by internal validation (C-index = 0.97).

Conclusion: Clinically, the 7-point improvement in HSS scores observed in Group B corresponds to a transition from 'poor' to 'good' knee function, while the 0.8-unit increase in femoral neck T-score translates into a 30% reduction in major-fracture risk over 10 years (FRAX-adjusted), indicating meaningful gains in patient mobility, pain relief, and long-term skeletal protection.

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Abstract: Alongside pulmonary and nutritional benefits, highly effective modulator therapies (HEMT) can promote an increase in body fat and raise the prevalence of overweight/obesity, dyslipidemia, and hypertension in patients with cystic fibrosis. These metabolic changes will theoretically elevate cardiovascular risk in a population that has largely been unaffected by such complications until now. A rise in the prevalence of metabolic syndrome among HEMT-treated patients is expected, which has already prompted a review of dietary recommendations. Thus, a distinction must be made between patients with several years of care experience and those, especially younger patients or those with a late diagnosis of cystic fibrosis, who have not been educated on the principle of a high-calorie diet. Whether these metabolic changes will result in a greater incidence of cardiovascular events remains uncertain, underscoring the need to validate predictive risk scores in this context.

Objective: Primary aldosteronism (PA) caused by a unilateral aldosterone-producing adrenal adenoma is potentially curable by surgery. Radiologically visible adrenal adenomas are not necessarily functional, so adrenal vein sampling (AVS) is recommended to lateralise aldosterone excess. However, AVS is technically challenging and limited in availability. We sought to evaluate the diagnostic accuracy of published algorithms for lateralisation without AVS and identify the top-performing algorithms with the highest specificity.

Design: Systematic review and meta-analysis.

Methods: Algorithms to predict unilateral PA and enable lateralisation without AVS, using AVS with or without surgical outcomes as the comparator, were systematically evaluated. Meta-analysis and meta-regression were conducted to obtain and compare aggregated estimates, respectively.

Results: There were 43 studies evaluating 30 unique algorithms grouped into four categories: i) those combining biochemical, radiological and demographic characteristics; ii) algorithms involving confirmatory testing or adrenocorticotropic hormone stimulation; iii) anatomical imaging; and iv) functional imaging. The meta-analysis demonstrated the highest specificity (95%) in the first two categories. The algorithm with the highest specificity (98%) for unilateral PA consisted of an adrenal nodule on CT, plasma aldosterone concentration >20.0 ng/dL (554 pmol/L), hypokalaemia (≤3.5 mmol/L) and renin concentration ≤5 mIU/L. Anatomical imaging for subtyping had poor specificity (69%), while functional imaging had higher specificity (86%), noting variation in functional imaging modalities and criteria for lateralisation.

Conclusions: Algorithms may be used to identify unilateral PA without invasive testing in a modest proportion of patients. Validation in different populations is required to enable the widespread use of these tools.

Significance statement: PA is gaining recognition as an important cause of hypertension and cardiovascular disease. The bottleneck created by AVS to subtype PA leads to delays in diagnosis and treatment. Selecting patients likely to have a unilateral aldosterone-producing adrenal adenoma, who can bypass AVS, will facilitate prompt surgical treatment and optimize the use of healthcare resources. Incorporating algorithms into the diagnostic evaluation of PA could streamline patient care and expedite appropriate treatments that will minimise the sequelae of aldosterone excess.

Background: Type 2 diabetes mellitus (T2DM) poses a significant global public health burden, where early detection of at-risk populations is imperative for implementing targeted preventive strategies. This systematic review and meta-analysis aimed to evaluate the methodological quality and predictive performance of existing T2DM risk prediction models in screening contexts.

Methods: Following the TRIPOD-SRMA statement, eligible studies were selected through searching seven databases (CNKI, WanFang Database, VIP, PubMed, Embase, Web of Science, and the Cochrane Library) from database inception through December 2024. Methodological quality was assessed using the PROBAST tool. Random-effects models synthesized discrimination (AUC). Subgroup analyses explored geographic, modeling, and validation-related heterogeneity. Funnel plots and Egger's regression test assessed small-study effects.

Results: A total of 65 studies (encompassing 97 distinct prediction models) were included in the analysis. Among 97 models, logistic regression dominated (97.9% of models), achieving moderate discrimination (AUC: 0.628-0.916), while machine learning (ML) models showed marginally higher AUCs (up to 0.998). Geographic and cohort disparities emerged, with USA-based models outperforming others (USA AUC: 0.97 vs China AUC: 0.79) and poor performance in prediabetic cohorts (AUC: 0.72 vs 0.80 in normoglycemic). External validation remained limited (21 models), though spatial/temporal validation cohorts demonstrated stable performance. High risk of bias and application (>80% of models) stemmed from inadequate statistical reporting and external verification definitions.

Conclusion: ML has favorable diagnostic accuracy for the progression of T2DM. This provides evidence for the development of predictive tools with broader applicability. Future research should prioritize external validation to enhance precision.

Context: Hypothalamic syndrome (HS) is a rare endocrine disorder resulting from Prader-Willi syndrome (PWS), craniopharyngiomas, ROHHAD syndrome, and unknown etiologies. Oxytocin has been shown to facilitate weight loss in children with HS and affect behavior. In this study, we aimed to observe the efficacy and safety of oxytocin treatment in HS patients, including those with PWS.

Case description: We described four PWS patients and nine non-PWS patients who received oxytocin treatment (16-24 IU/day) for 6 months. Two patients with ROHHAD syndrome were followed up for 1 year. Overall, patients exhibited reductions in BMI z-score ((4.36 (1.16, 13.18)) vs (4.20 ± 2.62)), Hyperphagia Questionnaire for Clinical Trials (HQ-CT) ((16.00 ± 8.59) vs (11.3 ± 6.31)), PWS Behavioral Questionnaire (PWSBQ) ((56.75 ± 27.24) vs (44.25 ± 23.89)) and the Epworth Sleepiness Scale (ESS) ((14.63 ± 42.55) vs (12.87 ± 5.77)), but some reversed at 6 months. Autonomic dysregulation in non-PWS patients improved at 3 months and remained stable at 6 months. No severe advance effects were observed.

Conclusion: Our study demonstrated that intranasal oxytocin administration improved appetite, behavioral symptoms, and sleep quality in the majority of patients. Notably, autonomic dysregulation was also alleviated in non-PWS cases, suggesting its potential as an alternative therapy for specific HS subtypes. However, further validation through larger-scale studies and extended follow-up is warranted to confirm its efficacy.

Infertility is a common issue that affects approximately 30 million men worldwide, most often resulting from defects during spermatogenesis, a complex cellular differentiation process allowing the formation of spermatozoa. During spermatogenesis, a large number of proteins involved in sperm production are phosphorylated, mainly on serine and threonine residues. As recently shown, this phosphorylation process is essential for male fertility. Protein phosphorylation depends on a balance between kinase and phosphatase activity, and although the kinases involved are relatively well characterized, much less is known about the presence and role of serine/threonine phosphatases within male germ cells. The aim of this review is to highlight the importance of protein phosphatase 2A (PP2A) in male fertility through direct expression of several PP2A subunits in male germ cells. First, the review will provide current knowledge on PP2A structure and regulation. Then, the importance of PP2A for spermatogenesis will be illustrated by the description of gene mutations and deletions recently identified in PP2A that result in male infertility, both in humans and mice. The review will also provide information on the level and stage of expression of PP2A subunits and endogenous inhibitors in human male germ cells, indicative of their dynamic regulation throughout spermatogenesis. Finally, the review will explore the involvement of PP2A beyond spermatogenesis during sperm maturation processes. Overall, this review highlights the critical functions of PP2A in male germ cells, reinforcing the importance of investigating the potential pathogenic deregulation of PP2A activity in cases of human male infertility.

Abstract: BRG1/BRM-associated factor (BAF) chromatin remodeling complexes are essential for normal endocrine function and are implicated in various metabolic and developmental disorders. However, the full range of chromatin-based regulatory programs and their molecular configurations in endocrine development remains unclear. In this study, we developed a computational pipeline to analyze bulk RNA-seq data from 45 human tissues and constructed tissue-specific co-expression networks for 30 core BAF complex genes. Using co-expression network analysis and Louvain clustering, we identified co-expression patterns that formed coherent gene communities for each tissue, comprising different combinations of 46 curated BAF subcomplex genes. In metabolically active non-endocrine tissues (kidney, skeletal muscle, vasculature, and fibroblasts), we observed strong co-expression with canonical BAF (cBAF) and polybromo-associated BAF (pBAF) gene communities. Central nervous system tissues were dominated by the neuron-specific BAF (nBAF) complex. Endocrine tissues (e.g., thyroid, adrenal) and gastrointestinal epithelia displayed co-expression profiles resembling smooth muscle-such as BAF and pBAF complexes, suggesting chromatin programs that integrate hormone secretion with contractile and barrier functions. These patterns show that each tissue exhibits a distinct, non-random combination of BAF subcomplexes, potentially reflecting its functional chromatin state. Our results demonstrate that latent patterns in tissue-specific gene expression profiles may reveal differences in protein complex regulation. The modular deployment of BAF chromatin remodeling complexes appears tailored to the functional demands of each organ. This study lays a foundation for further investigation of epigenetic regulation in endocrine development and pathobiological mechanisms and provides a framework for identifying tissue-specific chromatin remodeling strategies.

Plain language summary: The US National Institutes of Health has invested in large-scale measurements of how different human body tissues use their genetic material. The current study leverages per-tissue genomics data to better understand how various genes come together to form protein complexes, analogous to nanomachines, that in turn regulate the same genetic material. As the first research of its type, we focused on one category of protein complex, namely BAF, to develop the statistical approach needed.