Endocrine最新文献

Objective: Papillary thyroid cancer (PTC) progression is characterized by lymph node metastasis and thyroid capsular invasion. This study aimed to identify high-risk PTC populations for these events based on peripheral blood test parameters and to determine the associated factors.

Methods: This retrospective study analyzed data from 4557 PTC patients. Principal component analysis (PCA) and cluster analysis were performed on 45 peripheral blood test results. High- and low-risk clusters were defined based on metastasis and invasion prevalence. Univariate and multivariate analyses identified parameters significantly differentiating the clusters, examining their association with tumor progression.

Results: Preoperative blood tests stratified patients into two distinct clusters. Cluster 0 demonstrated significantly higher rates of metastasis and invasion than Cluster 1, defining it as the high-risk group. PCA identified four principal components significantly differentiating the clusters. Analysis of these components revealed key peripheral blood parameters. Multivariable logistic regression identified six parameters associated with increased risk of Cluster 0: alanine aminotransferase, free triiodothyronine, thrombin time, hemoglobin, hematocrit, and leukocyte count. Conversely, aspartate aminotransferase and neutrophil count were associated with decreased risk.

Conclusion: These findings suggest that peripheral blood parameters may provide insights into the progression of thyroid tumors and highlight potential avenues for exploring the underlying mechanisms of PTC. However, given the retrospective nature of this study and the potential for selection bias, further prospective studies are necessary to validate these results and confirm their predictive value in clinical practice.

The aim: to assess quality of life (QoL) and profile of mood states in patients with childhood-onset hypopituitarism and growth hormone (GH) deficiency during the discontinuation of recombinant growth hormone (rGH) replacement therapy at the transition from adolescence to adulthood.

Methods: mood states and QoL were assessed in 136 (85 men, 51 women, age 16.8 ± 1.1 years) patients during discontinuation of rGH replacement and 82 (40 men, 42 women, age 16.5 ± 1.7 years) control individuals using the Profile of Mood States2 (POMS2) and the Quality of Life - Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) questionnaires.

Results: No difference in QoL was between patients and controls, but patients had higher levels of tension-anxiety (median 9.0 score vs. 6.0 score, p < 0.001), depression-dejection (median 9.0 score vs. 8.0 score, p = 0.042), fatigue-inertia (median 9.0 score vs. 6.0 score, p < 0.001), confusion-bewilderment (median 4.0 score vs. 3.0 score, p = 0.003) than controls. Basal cortisol concentration correlated negatively with QoL-AGHDA score (r = -0.288, p = 0.012), depression-dejection score (r = -0.317, p = 0.005). Height correlated negatively with anger-hostility (r = -0.223, p = 0.010), fatigue-inertia (r = -0.188, p = 0.030) scores. Body mass index (BMI) correlated positively with fatigue-inertia score (r = 0.181, p = 0.040). Age at the discontinuation of rGH replacement correlated negatively with QoL-AGHDA score (r = -0.204, p = 0.026), depression-dejection (r = -0.460, p = 0.021), anger-hostility (r = -0.190, p = 0.040), fatigue-inertia (r = -0.205, p = 0.026) scores.

Conclusion: mood states (higher tension-anxiety, depression-dejection, fatigue-inertia, confusion-bewilderment), but not disease-specific QoL are impaired in patients with childhood-onset growth hormone deficiency during the discontinuation of rGH replacement therapy at the transition from adolescence to adulthood.

Purpose: To evaluate organ-specific response to [¹⁷⁷Lu]DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) in patients with small intestine neuroendocrine tumor (SiNET) through [⁶⁸Ga]DOTATOC PET/CT, and to analyze tumor uptake and functional volume variations at different metastatic sites in relation to disease progression during clinical follow-up after treatment.

Methods: A retrospective analysis was conducted on 33 metastatic patients. PET/CT were performed pre-treatment (PET0), mid-treatment after two PRRT cycles (PET2), and post-treatment (PET4). SUV_max and somatostatin receptor-expressing tumor volume (SRETV) were measured in liver, lymph node, peritoneum/mesentery, and bone metastases.

Results: Liver metastases showed significant reduction in both SUV_max and SRETV from PET0 to PET4, with early response evident after two PRRT cycles. Nodal lesions exhibited a delayed response, with significant reductions at PET4. Peritoneal and bone metastases showed a continuous decline in SUV_max, but no significant changes in SRETV. Objective response rates were highest in liver metastases after treatment completion with lesser responses in nodal, peritoneal, and bone lesions. At a median follow-up of 24.3 months, 70% of patients experienced disease progression, while 30% did not. Liver metastases showed no significant changes in SUV_max or SRETV regardless of progression. Conversely, in non-progressing patients, peritoneal/mesenteric lesions showed a significant reduction in SUV_max, with unchanged SRETV, and nodal metastases exhibited reduced SRETV. Bone lesions in non-progressing patients showed significant decreases in both SUV_max and SRETV.

Conclusion: [¹⁷⁷Lu]DOTATATE PRRT effectively reduces tumor functional activity in patients with SiNETs, with organ-specific responses highlighting the need for personalized treatment strategies to optimize efficacy and minimize toxicity.

Background: Sedentary behavior has emerged as a potential risk factor for various health issues, including hormonal imbalances like testosterone deficiency (TD). However, the relationship between sedentary time and TD remains underexplored, especially with respect to the complex biological mechanisms underlying this association. This study aimed to examine the association between sedentary time and TD in adult males.

Methods: This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey 2011-2016. A total of 6057 male participants aged 20 years and older were included. Sedentary time was categorized into quartiles, and TD was defined as serum testosterone levels below 300 ng/dL. Logistic regression models were employed to assess the association between sedentary time and TD, adjusting for demographic, lifestyle, and health-related covariates. Restricted cubic spline (RCS) analysis and segmented regression were also conducted to explore potential non-linear relationships and thresholds. Subgroup analyses were performed to examine the consistency of associations across various groups.

Results: The analysis revealed a significant positive association between sedentary time and TD. Prolonged sedentary behaviour was consistently associated with higher odds of TD across all models (all p < 0.001). RCS analysis showed a significant non-linear relationship, particularly as sedentary time exceeded 4.5 h per day, with a marked increase in the likelihood of TD (p-non-linear = 0.027). Subgroup analysis indicated that this association was most pronounced in Non-Hispanic Whites, current smokers, and drinkers, and was weaker in individuals with diabetes, where the association lost statistical significance after full adjustment.

Conclusions: This study identifies a significant association between prolonged sedentary behaviour and a higher risk of TD, suggesting that sedentary behavior may play a key role in the development of TD, particularly in specific high-risk populations.

Objective: This meta-analysis aimed to compare the efficacy and safety of iGlarLixi with those of insulin glargine for treating type 2 diabetes (T2D).

Methods: A systematic search of PubMed, the Cochrane Library, and EMBASE was conducted to identify randomized controlled trials (RCTs) that compared the use of iGlarLixi with the use of insulin glargine in patients with T2D. The meta-analysis protocol was registered at PROSPERO. The primary outcomes of interest were changes in hemoglobin A1c (HbA1c) and body weight. Risk ratios and mean differences with 95% confidence intervals were calculated using random-effects models.

Results: We included 7 RCTs comprising 2229 men and 1926 women, of whom 2075 (49.94%) were randomized to iGlarLixi. Compared with insulin glargine, iGlarLixi decreased HbA1c (MD: -0.50%; 95% CI: -0.65% to -0.35%; p < 0.00001) and body weight (MD: -1.17 kg; 95% CI: -1.36 kg to -0.98 kg; p < 0.00001) and self-measured plasma glucose (MD: -0.97 mmol/L; 95% CI: -1.27 mmol/L to -0.68 mmol/L; p < 0.00001) and increased the percentage of patients achieving HbA1c < 7% (RR: 1.66; 95% CI: 1.31 to 2.11; p < 0.0001), the percentage of patients achieving HbA1c < 6.5% (RR: 2.11; 95% CI: 1.53 to 2.92; p < 0.00001), and HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes (RR: 2.18; 95% CI: 1.76 to 2.69; p < 0.00001). However, a higher incidence of gastrointestinal adverse events (RR: 2.02; 95% CI: 1.61 to 2.54; p < 0.00001) and adverse events (RR: 1.08; 95% CI: 1.02 to 1.14; p = 0.008) was associated with iGlarLixi than with insulin glargine.

Conclusions: Compared with insulin glargine, iGlarLixi is superior in reducing blood glucose levels and facilitating weight loss. Nevertheless, its administration is also linked to a heightened occurrence of gastrointestinal and adverse events.

Purpose: Patients with adrenal insufficiency (AI) are known to have a higher cardiovascular risk (CVR) than the normal population. In particular arteriosclerosis, coronary heart disease, arterial hypertension, hyperlipoproteinemia as well as metabolic disturbances contribute to the increased morbidity and mortality. Aim of this study was to evaluate known CVR factors along with the quality of care by the treating physicians.

Methods: To this end the medical records of AI patients were screened for CVR factors and the treatment initiated was documented. In addition, a questionnaire evaluating CVR factors was analyzed if available.

Results: In total, 327 AI patients were included in the study. At least 298 of these patients were found to have one or more CVR factors. Ninety-one patients were diagnosed with arterial hypertension, of these 40 patients (44%) still showed increased blood pressure (BP) values. Of all AI patients, about 25% (n = 83) did not have measurements to calculate their BMI, even though obesity is known as a major risk factor for cardiovascular events. Out of 46 patients with diabetes, one-quarter still had increased HbA1c values. Regarding hyperlipoproteinemia, only 2% of AI patients achieved normal lipid values across all parameters (n = 8). Interestingly, at least one lipid variable was untested in 150 patients (46%).

Conclusion: Our study demonstrates (1) the high rate of CVR factors in AI patients, leading to increased morbidity and eventually mortality, (2) AI patients are inadequately monitored and treated for CVR factors, (3) treating physicians should be aware of this risk to minimize complications where possible.

Introduction: Mild autonomous cortisol secretion (MACS) is associated with several cardiometabolic and non-metabolic comorbidities, including osteoporosis, fractures and worse quality of life (QoL).

Methods: We performed a comprehensive review of the literature including articles that reported the association between MACS and osteoporosis, fractures and impact on QoL.

Results: In relation to bone health, several studies reported that the risk of fractures in patients with MACS is discordant with the degree of bone mineral density loss measured per dual X-ray absorptiometry (DXA), suggesting that a reduction in bone quality rather than density contributes to the increased fracture risk. Nevertheless, in general a greater prevalence of vertebral fractures has been described in MACS compared with nonfunctioning adrenal incidentalomas (NFAIs) patients. Regarding QoL, due to the higher burden of comorbidities and the adverse symptoms linked to MACS diagnosis, MACS patients are overall frailer and have worse QoL than patients with NFAIs or the general population. Higher levels of disability related to mental health, middle insomnia and perceived stress have also been described in patients with MACS when compared to NFAIs patients.

Conclusion: MACS patients have a higher prevalence of fractures and osteoporosis, as well as a worse QoL compared to NFAIs and the general population. Thus, both bone health and QoL evaluation should be part of the assessment of patients with MACS diagnosis.

Background: Obesity is among the important healthcare issues in which there is an abnormal increase in body fat because energy intake is higher than energy expenditure. The Tumor Necrosis Factor (TNF)-alpha overexpression in adipose tissue plays important roles in mediating obesity and insulin resistance. "TNF-related apoptosis-inducing Ligand (TRAIL(TNSF10))", which is a member of the TNF family, is expressed as a Type-II Transmembrane Protein with an effect on the development of obesity and diabetes.

Methods: The rs781673405, rs1244378045, rs767450259, rs750556128, rs369143448, rs143353036, and rs759369504 polymorphisms of TRAIL, which were determined to play protective roles against diabetes, were evaluated with the RT-qPZR Method in the present study.

Results: It was found that the genotype distribution of TRAIL rs767450259 Polymorphism was significant and the T-Allele had protective effects against diabetic obesity. It was also found that the G-Allele of the rs369143448 Polymorphism had protective roles against diabetic obesity. It was shown that carrying the A-Allele in the rs750556128 Polymorphism might increase the risk of obesity in diabetic patients by 1.3-fold.

Conclusions: The present study makes a significant contribution to the literature data because it is the first to investigate these polymorphisms.

Purpose: Parathyroid hormone controls calcium and phosphate metabolism. The latter is also regulated by both FGF23 and 1-25(OH)₂VitaminD. The polymorphic variant c.716 C > T of the FGF23 gene was previously found to be associated with renal phosphate leak/nephrolithiasis. The aim of our research is to study the metabolism of phosphate in a cohort of patients with primary hyperparathyroidism (PHPT) and its impact on bone and kidney.

Methods: We have retrospectively compared a large sample of sporadic PHPT patients (339) with historical comparison cohort (HCC 503: Olivetti Study Group and Siena Osteoporosis Study). Moreover, in 51 PHPT patients, phosphate metabolism indexes were also revaluated at least 2 years after surgical cure. The variant c.716 C > T of the FGF23 gene was genotyped in patients and in a small sample of the control group.

Results: In PHPT patients we found higher levels of serum calcium, PTH, alkaline phosphatase, beta-C-terminal telopeptide (CTx), urinary calcium, while serum phosphate, 25OH-VitaminD, maximal tubular renal phosphate reabsorption adjusted for glomerular filtration rate (TmPO4/GFR) were lower than what was found in HCC. In PHPT patients fibroblast growth factor 23 (FGF23) levels were higher than in controls. Patients with kidney stones carried the 716 T allele more frequently than patients without it (χ² 7.20, p = 0.027). In PHPT patients revaluated at least 2 years after surgery, we observed a significant reduction of 1-25(OH)₂VitaminD and FGF23. According to the median of serum phosphate levels, PHPT patients were subdivided into two subgroups: ≤2.8 mg/dL and > 2.8 mg/dL. The lowest phosphate group had a significantly higher serum calcium, PTH, 1-25(OH)₂VitaminD, urinary calcium and a higher prevalence of kidney stones than in the highest phosphate group. The rate of males in the lowest phosphate group was significantly higher than in the highest phosphate group.

Conclusion: Our study shows that the regulators of phosphate metabolism in PHPT patients are higher than controls and they significantly reduce after surgical cure. PHPT patients with low serum phosphate have a worse biochemical and clinical phenotype.

Purpose: Locally advanced thyroid cancer (LATC) has gained increased attention, yet factors influencing invasion patterns and their prognostic impact remain poorly understood.

Methods: Patients with LATC were identified from the Surveillance, Epidemiology, and End Results (SEER) program. Invasion patterns were visualized using bar graphs. Kaplan-Meier method and log-rank test analyzed outcomes by different invasion sites. Multivariable Cox regression analysis was conducted to adjust confounding factors and establish a new site-based risk stratification.

Results: Papillary thyroid carcinoma (PTC) predominantly invaded esophagus or larynx (21.0%) and trachea (26.3%), while follicular thyroid carcinoma/oncocytic thyroid carcinoma (FTC/OTC) mainly invaded blood vessel (31.3%). Anaplastic thyroid carcinoma (ATC) exhibited the highest rate of trachea invasion (33.3%) and multi-invasion (8.1%). Age, tumor size significantly influenced the proportion of trachea invasion (p < 0.001). Locally advanced PTC patients with different invasion sites demonstrated significantly different prognoses: 10-year OS rate of each invasion site was: parathyroid or nerve (82.5%), bone or skeletal muscle (76.6%), esophagus or larynx (68.7%), blood vessel (58.0%), trachea (57.5%), multi-invasion (26.8%). Based on multivariable Cox regression, a novel site-based risk stratification was established for locally advanced PTC patients, with trachea invasion (HR = 1.83, p < 0.001), blood vessel invasion (HR = 2.64, p < 0.001), and multi-invasion (HR = 2.76, p < 0.001) categorized as medium and high risk of mortality, respectively, demonstrating better discrimination than 8th AJCC staging system.

Conclusion: This study is the first to utilize population-based cohort to reveal factors influencing invasion sites and their prognostic differences. This study also proposed a new site-based risk stratification that builds upon 8th AJCC T staging for locally advanced PTC patients, which may facilitate more tailored clinical management strategies.