Endocrine最新文献

Objective: This study aimed to develop and evaluate machine-learning models for predicting the onset of overweight in adolescents aged 14‒17, utilizing easily collectible personal information.

Methods: This study was a one-year prospective cohort study. Baseline data were collected through anthropometric measurements and questionnaires, and the incidence of overweight was calculated one year later via anthropometric measurements. Predictive factors were selected through univariate analysis. Six machine-learning models were developed for predicting the onset of overweight. The SHapley Additive exPlanations (SHAP) was used for global and local interpretation of the models.

Results: Out of 1,241 adolescents, 204 (16.4%) were identified as overweight after one year. Nineteen features were associated with the overweight incidence in univariable analysis. Participants were randomly divided into a training group and a testing group in a 7:3 ratio. The Light Gradient Boosting Machine (LGBM) algorithm achieved outperformed other models, achieving the following metrics: Accuracy (0.956), Recall (0.812), Specificity (0.983), F1-score (0.855), AUC (0.961). Importance ranking revealed that the top 11 minimal feature set can maintain the stability of model performance.

Conclusions: The onset of overweight in adolescents was accurately predicted using easily collectible personal information. The LGBM-based model exhibited superior performance. Oversampling technique notably improved model performance. The model interpretation technique provided innovative strategies for managing adolescent overweight/obesity.

Purpose: To identify clinical, biological and pathological risk factors for the incidental discovery of papillary thyroid microcarcinomas (PTMCs) in patients undergoing thyroidectomy for presumed benign conditions.

Methods: Cross sectional, single center study, involving all consecutive patients (N = 3015) who were submitted to thyroid surgery between 2001-2019. All medical files were retrospectively reviewed. A total of 1961 patients in the benign group and 145 patients in PTMC group were analyzed.

Results: No significant differences in age, sex, body mass index, smoking status, thyroid volume or weight and preoperative thyroxine treatment between benign and PTMC groups were observed. Circulating anti- thyroid antibodies, histological thyroiditis and serum thyrotropin (TSH) were significantly associated with PTMC in univariable analysis. Independent risk factors for incidental PTMC by multivariable analysis where possible (OR: 1.51, 95% CI: 0.99-2.28) and certain (OR: 1.74, 95% CI: 1.09-2.78) thyroid autoimmunity (p = 0.002) and higher serum TSH (OR: 1.25, 95% CI: 1.08-1.45, p = 0.03), whereas thyroid lobectomy was associated with a lower risk of PTMC (OR: 0.40, 95% CI: 0.24-0.67, p < 0.001). The most frequent genetic alteration was BRAF^V600E mutation, found in 56.3% of PTMC submitted to DNA sequencing. No association between clinical, biological or histological characteristics of PTMC and BRAF^V600E mutation was observed.

Conclusions: Thyroid autoimmunity and higher preoperative serum TSH level were independent predictors of PTMC incidentally discovered during thyroid surgery. Larger prospective studies are needed to better identify possible risk factors for papillary thyroid carcinoma initiation and progression.

Purpose: Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile.

Methods: We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment.

Results: Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response.

Conclusion: In a developing country, TL is an adequate option for appropriately selected DTC patients.

Purpose: Alpelisib is a PI3K (Phosphoinositide 3-kinases) inhibitor used for breast cancer which develops hyperglycemia based on its action on glucose metabolism regulation. This study aims to identify potential risk factors predicting hyperglycemia development and the need for multiple treatments for hyperglycemia in patients receiving Alpelisib.

Methods: Fourteen women diagnosed with metastatic hormone receptor-positive breast cancer carrying PI3K mutations who initiated treatment with Alpelisib were monitored through consultations in the Oncology and Endocrinology departments. Non-parametric ROC curves were generated to assess the need for three or more antidiabetic medications to achieve glycemic control.

Results: The study population had a median age of 64 years (range:48-69) with a median body mass index (BMI) of 26.6 kg/m² (range: 22.9-29.4). Overweight was observed in 35.7% of the participants and obesity in 21.4%. Fifty percent of the participants had prediabetes, and 85.7% developed hyperglycemia requiring pharmacological treatment, although none of them needed to discontinue treatment for this reason. Baseline C-peptide levels and BMI were associated with the number of antidiabetic drugs used (Spearman's Rho 0.553, p = 0.040; Spearman's Rho 0.581, p = 0.030, respectively). ROC curve analysis showed and area under the curve (AUC) of 0.819 for the variable risk profile (defined as baseline C-peptide >10.5 ng/ml and BMI > 27 kg/m²), whereas AUC values were 0.556 and 0.514 for HbA1c and baseline glucose, respectively, (p = 0.012).

Conclusion: A joint follow-up by an Oncology department and a Diabetes Unit can prevent treatment discontinuation in patients under Alpelisib therapy. Baseline BMI and plasma C-peptide levels can predict an increased need for anti-hyperglycemic treatment.

Purpose: Aimed to create a nomogram using clinical and eye-specific metrics to predict the efficacy of intravenous glucocorticoid (IVGC) therapy in patients with active and moderate-to-severe Thyroid-Associated Ophthalmopathy (TAO).

Methods: This study was conducted on 84 eyes from 42 moderate-to-severe TAO patients who received systemic IVGC therapy, and 42 eyes from 21 controls. Data were collected retrospectively from June 2020 to December 2021. The least absolute shrinkage and selection operator (LASSO) method was used to identify predictive factors for "unresponsiveness" to IVGC therapy. These factors were then analyzed using logistic regression to create a nomogram. The model's discriminative ability was robustly assessed using a Bootstrap resampling method with 1000 iterations for receiver operating characteristic (ROC) curve analysis.

Results: The LASSO analysis identified six factors with non-zero coefficients as significant, including Schirmer I test values, Meibomian gland (MG) diameter, MG length, disease duration, whole capillary vessel density (VD) in the radial peripapillary capillary (RPC), and whole macular VD for the superficial retinal capillary plexus (SRCP). The subsequent logistic regression model highlighted MG length, whole macular VD for SRCP, and disease duration as independent predictors of IVGC therapy response. The constructed nomogram demonstrated an area under the curve (AUC) of 0.82 (95% CI: 0.73-0.91), affirming the model's consistent and reliable ability to distinguish between responsive and non-responsive TAO patients.

Conclusion: Our nomogram, combining MG length (<4.875 mm), SRCP VD (<50.25%), and disease duration (>5.5 months), reliably predicts lower IVGC therapy effectiveness in active, moderate-to-severe TAO patients.

Objective: To study whether subcutaneously embedding xenogeneic protein threads or synthetic polymer absorbable threads can improve obesity phenotypes and metabolic conditions, and to further explore its underlying mechanism.

Methods: Thirty-six 8-week-old ob/ob mice were randomly allocated to three groups, respectively, receiving catgut embedding, PGA thread embedding or sham treatment bilaterally to the groin. Individual parameters including weight, food intake, and core temperature are recorded and metabolism assessment, energy expenditure analysis, and PET/CT scanning are also performed at fixed timepoints. After surgical incision, the inguinal white adipose tissue was histologically examined and its expression profile was tested and compared among groups 4 weeks and 12 weeks after operation.

Results: Catgut embedding reduced weight gain and improved metabolic status in ob/ob mice. Browning of bilateral inguinal WAT (white adipose tissue) was induced after catgut embedding, with massive infiltration of Treg cells and M2 macrophages in the tissue slices of fat pads. IL-10 and TGF-β released by Treg cells targeted macrophages and the induced M2 macrophages increased the expression of thermogenic and anti-inflammatory genes in fat. The secretion of catecholamines by polarized M2 macrophages led to the activation of β3-AR-related pathways in adipocytes and the browning of adipose tissue.

Conclusions: Abdominal subcutaneous catgut embedding has the potential to combat obesity through the induction of WAT browning mediated by infiltrated Treg cells and macrophages.

Introduction: Pregnancy and lactation-associated osteoporosis (PLO) is a rare condition characterized by fragility fractures occurring during late pregnancy or lactation, primarily affecting the spine and causing significant morbidity and back pain. PLO can lead to mobility impairment and work incapacity, with recovery taking up to several years. Due to the lack of clinical trials, treatment strategies remain poorly defined, historically focusing on calcium supplements, vitamin D, and weaning from breastfeeding. However, recent attention has turned to teriparatide (TPD) as an option due to its anabolic properties and potential suitability for women of childbearing age.

Methods: This review evaluates TPD's use in PLO treatment, using published systematic reviews and case studies. Over 300 cases with PLO were identified through PubMed, Google Scholar, and Cochrane searches until August 2023.

Results: We identified 175 cases with PLO treated with TPD alone or followed by antiresorptive therapy. Most women (85.7%) were primiparas. The mean ± SD duration of TPD use was 15 ± 6 months. Among the study patients, 91.4% used TPD alone, while 8.6% (15/175) utilized sequential therapy. Approximately 93% of our cohort exhibited potential risk factors for PLO. Despite the increased risk of recurrent fractures in PLO, only 14.7% (20/175) of those treated with TPD sustained new fractures during a 9-month to 9 years' follow-up period. The mean ± SD percent increase in BMD at the LS was 21.14% ± 7.4%, and at the FN it was 12.1% ± 9.3%. The baseline Z-scores at the LS ranged from -3.3 (-3.7 to -2.7), while the baseline Z-scores at the FN ranged from -2.0 (-2.7 to -1.5).

Conclusion: This review emphasizes PLO severity, advocating for increased awareness and timely interventions. TPD emerges as a promising therapeutic option in certain cases.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, posing a growing clinical challenge. PTC exhibits two age-related peaks, with established risk factors including family history and radiation exposure. Managing even low-risk, localized PTC cases remain complex, with growing interest in active surveillance as an alternative to immediate surgery. This study employed single-cell RNA sequencing (scRNA-Seq) to explore the predictive value of BRAF and RAS mutations in PTC, shedding light on their impact on disease progression and outcomes. The analyses emphasized the significance of BRAF and RAS mutations in tumor advancement, particularly the unique BRAF V600E mutation associated with aggressive features. The methodology involved scRNA-Seq analysis of PTC and normal samples, unveiling distinct cell clusters and indicating upregulated BRAF and RAS genes. Pathway enrichment analysis highlighted altered biological processes and immune-related pathways in PTC. The study consolidated previous research showing the prevalence of BRAF and RAS mutations in PTC, subtypes with distinct molecular profiles, and the impact of TERT promoter mutations on disease severity. In summary, this study unveils the complex interplay of genetic mutations and the cellular microenvironment in PTC through scRNA-Seq. The upregulated BRAF and RAS genes suggest their roles as PTC drivers, and pathway enrichment reveals alterations in immune-related processes. This synthesis of prior research enhances our understanding of PTC's molecular foundations, informing better prognosis and personalized treatment approaches. These insights advance the landscape of PTC management and provide directions for further research.

Background: The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery.

Methods: This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS).

Results: Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan-Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44-0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19-12.84]).

Conclusions: RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans.

Immune checkpoint inhibitors (ICIs) have become extensively utilized in the early-stage treatment of various cancers, offering additional therapeutic possibilities for patients with advanced cancer. However, certain patient populations are susceptible to experiencing toxic adverse effects from ICIs, such as thyrotoxicosis, rashes, among others. Specifically, ICIDM, induced by immune checkpoint inhibitors, exhibits characteristics similar to insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). ICIDM is characterized by a rapid onset and may coincide with severe ketoacidosis. Despite a favorable response to insulin therapy, patients typically require lifelong insulin dependence. After discussing the autoimmune adverse effects and the specifics of ICIs-induced diabetes mellitus (ICIDM), it is important to note that certain patient populations are particularly susceptible to experiencing toxic adverse effects from ICIs. Specifically, ICIDM, which is triggered by immune checkpoint inhibitors, mirrors the characteristics of insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). This article conducts an in-depth analysis of the literature to explore the pathogenesis, disease progression, and treatment strategies applicable to diabetes induced by immune checkpoint inhibitors (ICIDM).