Endocrine Connections最新文献

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease globally, with over 20% of patients progressing to metabolic dysfunction-associated steatohepatitis (MASH), which carries a high risk of cirrhosis and hepatocellular carcinoma. While liver biopsy remains the gold standard for MASH diagnosis, its invasiveness and limitations necessitate reliable noninvasive alternatives. This study aimed to develop a cost-effective biomarker panel using routine laboratory tests to distinguish MASLD severity stages.

Methods: We conducted a single-center, retrospective study of 209 biopsy-proven MASLD patients, stratified by NAS: simple steatosis (NAS <3, n = 40), borderline (NAS 3-4, n = 120), and definitive MASH (NAS ≥5, n = 49). Clinical, biochemical, hematologic parameters and metabolic markers were analyzed. Logistic regression and ROC curves assessed diagnostic performance.

Results: Key findings revealed progressive increases in BMI, ALT, AST, and transferrin (Tf) levels with disease severity. Multivariate logistic regression identified ALT and Tf as independent predictors for borderline and MASH. Notably, ALT showed superior diagnostic performance for distinguishing simple MASLD with borderline (AUC 0.763), while Tf was most effective for MASH detection (AUC 0.723). A combined model integrating BMI, ALT, and Tf demonstrated excellent diagnostic accuracy for borderline (AUC 0.840) and MASH (AUC 0.805).

Conclusion: Our study highlights that a simple, cost-effective panel of routinely available biomarkers (BMI, ALT, and Tf) can effectively stratify MASLD progression, offering a practical alternative to invasive diagnostics. This approach enhances early MASH detection, facilitating timely clinical intervention.

Subclinical hypothyroidism is characterized by elevated thyroid stimulating hormone (TSH) levels and normal FT4, and is associated with an increased risk of cardiovascular diseases, but its specific impacts on the right ventricle and underlying mechanisms remain unclear. This study aimed to investigate the direct role of TSH signaling through its receptor in right ventricular hypertrophy and energy metabolism remodeling. A model of pulmonary arterial hypertension-induced right ventricular injury was created in male cardiomyocyte-specific TSH receptor knockout mice and control mice using Sugen5416 combined with hypoxia (10% O2). Cardiac function was assessed via echocardiography, while histological and molecular changes were examined through staining techniques, quantitative PCR, and Western blot. Metabolic alterations were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. Results demonstrated that pulmonary hypertension induced right ventricular dysfunction, hypertrophy, and metabolic dysregulation in control mice, characterized by impaired systolic and diastolic function, increased glycolytic enzyme expression, lactate accumulation, and reduced ATP levels. These pathological changes were significantly attenuated in TSH receptor knockout mice. In vitro, TSH treatment promoted hypertrophic marker expression and shifted metabolic activity toward glycolysis in H9c2 cardiomyocytes. In conclusion, our in vivo and in vitro experiments demonstrate that TSH promotes cardiomyocyte hypertrophy and upregulates the glycolytic pathway. These findings reveal a direct contribution of elevated TSH to right ventricular injury and may offer novel mechanistic insights into right ventricular impairment associated with subclinical hypothyroidism.

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.