Minerva endocrinology最新文献

Background: The Pituitary Tumors Centers of Excellence (PTCOE) concept was established to provide a multimodal approach with careful management of comorbidities. Acromegaly, one of the main concerns of PTCOE per se, leads to increased mortality rates of which cardiovascular disease is an important cause. Increased skin autofluorescence (SAF) was shown to be associated with carotid intima-media thickness (CIMT), a well-established marker of atherosclerosis, and consequently cardiovascular complications. This study aimed to evaluate SAF and CIMT in association with anthropometric, clinical, and biochemical parameters in acromegaly patients and healthy controls.

Methods: The study group included 138 acromegaly patients and 127 healthy controls from the Department of Endocrinology and Metabolism Disease, Marmara University Medical School. Growth hormone, insulin-like growth factor I, lipids, glucose, insulin levels were assessed. Advanced glycation end products (AGEs) were measured by the auto-fluorescence reader. CIMT was measured from the common carotid artery wall on B-mode ultrasound.

Results: CIMT and SAF levels were significantly higher in the acromegaly group than the control group. There was a positive correlation between SAF and CIMT both in the total cohort and acromegaly patients. The presence of acromegaly, age, and SAF were the determining factors of CIMT in the whole study cohort.

Conclusions: Our study is the first to examine the relationship between SAF and CIMT in acromegaly patients. We found higher CIMT and enhanced SAF in the acromegaly group compared to the control group with a significant positive correlation in between. The presence of acromegaly was related to increased SAF levels and CIMT. SAF was associated with CIMT in acromegaly patients. Implementation of CIMT and SAF evaluation in this clinical setting may improve cardiovascular complications, particularly in the PTCOE.

Background: The aim of this study is to investigate the use of once-weekly semaglutide in a real population of patients with type 2 diabetes mellitus (T2DM) over 70 years in two Spanish hospitals.

Methods: An observational, retrospective, and multicenter clinical study was designed. It included 60 patients with T2DM, with a mean age of 76.5 years, 63.3% women, and a mean of 15.5 years of evolution of T2DM, all managed in the outpatient clinical setting. The primary endpoint was the change in HbA1c from baseline to the end of the study. The secondary endpoints included changes in body weight and the proportion of patients achieving HbA1c <7.0% and body weight loss >5%.

Results: After 12 months of follow-up, the reductions in HbA1c were -0.61±0.9% (P<0.0001) in the total cohort. Body weight reductions were -8.2±5.3 kg (P<0.0001). Overall, 67% reached the objective of an HbA1c level of <7%, and 73% achieved a weight loss of ≥5%.

Conclusions: In routine clinical practice in Spain, the use of semaglutide once a week was associated with statistically significant and clinically relevant improvements in HbA1c and body weight in adults aged over 70 years with T2DM, without notable adverse effects, which supports real-world use.

Background: Treatment of advanced differentiated thyroid carcinoma (DTC) remains a challenge as 25-50% of patients with locally invasive or distant metastatic disease become refractory to radioiodine (RAI) therapy. Tyrosine kinase inhibitors (TKI) are increasingly used in this setting. The SELECT trial demonstrated that lenvatinib, a multikinase inhibitor, significantly improved progression free survival (PFS) compared to placebo. Our aim was to report the effectiveness and safety of lenvatinib in our series of patients with advanced DTC.

Methods: A total of 25 patients with advanced DTC followed at a single tertiary center from January of 2016 to January of 2022 were retrospectively reviewed.

Results: Patients were treated with a mean daily dose of lenvatinib of 16.9 mg for a mean of 9.1 months. Median estimated PFS was 31.3 months. One patient achieved complete response. The objective response rate (ORR) was 40% and the disease control rate was 84%. The mean change in summed longest diameter of target lesions from baseline to nadir was -36.9%. Lenvatinib prolonged the tumor volume doubling time in 86.7% patients. Interestingly, we found that patients treated with a lower dose of lenvatinib (<16.9 mg daily) had a significantly higher PFS and ORR than patients treated with higher dosages (>16.9 mg). Adverse events were frequently reported.

Conclusions: Our results confirm the effectiveness of lenvatinib in the management of patients with advanced DTC and support the need to adjust the dosage of lenvatinib to patient's performance status and comorbidities.

Introduction: Advanced and progressive thyroid cancer (TC) such as radioiodine-refractory thyroid cancer (RAIR-TC), presents a significant clinical challenge due to its poorer prognosis and limited therapeutic options. Lenvatinib is an oral multi-targeted tyrosine kinase approved as first line for the treatment of RAIR-TC.

Evidence acquisition: We provide a comprehensive review of lenvatinib in the management of advanced thyroid cancer including RAIR-TC, poorly differentiated (PDTC), anaplastic (ATC) and medullary thyroid carcinoma (MTC). A search was carried out on PubMed up to July 2024 to identify all relevant studies. The research was performed using the terms "thyroid neoplasms" (MeSH Terms) AND "lenvatinib" (MeSH Terms).

Evidence synthesis: Lenvatinib demonstrated beneficial outcomes in treating RAIR-TC with most patients achieving either partial response or stable disease, which led to its approval by regulatory agencies worldwide. In PDTC, lenvatinib demonstrated potential therapeutic usefulness, whereas its efficacy as a monotherapy in ATC has yielded less consistent outcomes. However, in ATC the combination of lenvatinib with immune check point inhibitors (such as pembrolizumab) seem promising. In MTC, the available data is limited to phase II studies. Adverse effects of any grade occur in almost all lenvatinib-treated patients and mostly have a time specific sequence of occurrence. Therapy discontinuations due to adverse events are not uncommon, and in some cases, drug-related fatalities may occur.

Conclusions: Lenvatinib demonstrated clinical efficacy and safety in both clinical trials and real-world studies for the treatment of patients with different types of thyroid cancer.

Background: Sarcopenic obesity is closely related to metabolic dysfunction-associated steatotic liver disease (MASLD), but the independent contributions of lean mass and fat mass components to MASLD are not well understood. Our study aimed to evaluate the relationship between the dual-energy X-ray absorptiometry (DXA)-derived soft tissue components and the extent of liver steatosis in patients with MASLD.

Methods: A cross-sectional study of 118 obese/overweight patients aged 33-78 years, with type 2 diabetes mellitus (T2DM) or prediabetes and MASLD, on oral antidiabetic medication was conducted. Sex-stratified correlation analysis was performed between DXA-derived lean mass and fat mass parameters, (e.g., relative muscle mass [RMM], lean mass/ fat mass [LM/FM] and appendicular lean mass [ALM]), as well as between each of those parameters and the hepatic steatosis index (HSI). Multiple linear regression models were fitted with android fat percentage as the dependent variable, and lean mass indices as independent variables. The models were adjusted for age, sex, the HOMA index, triglyceride and ALT levels. Accordingly, ROC curves were plotted with HSI=36 as a classifier of steatosis.

Results: A significant negative correlation was detected between android fat % and RMM (r=-0,96, P≤0.001), between android fat percentage and ALM /BMI (r=-0.70, P≤0.001), between android fat percentage and ALM /height² (r=-0.28, P≤0.001); between HSI and RMM (r=-0.50, P≤0.001); and between HSI and ALM/BMI (r=-0.39, P≤0.001). The significant positive correlations were as follows: android fat percentage and BMI (r=0.53, P≤0.001); android fat % and ALT (r=0.25, P=0.04); HSI and android fat percentage (r=0.59, P≤0.001); HSI and gynoid fat % (r=0.39, P≤0.001). The AUCs for android fat percentage in the models calculated from LM/FM were as follows: adjusted for the HOMA index, age and sex group, ROC=0.748 (95% CI 0.66-0.83); adjusted for ALT and sex group, ROC=0.743 (95% CI 0.66-0.83). The AUC for android fat percentage in the model calculated from RMM: adjusted for triglycerides, ALT and sex group, ROC=0.741 (95% CI 0.65-0.83).

Conclusions: Our findings demonstrate that an increase in android fat distribution and a decrease in lean mass are positively associated with MASLD. The regression models support the utility of DXA-derived indices as practical, indirect markers of liver steatosis for clinical application in patients with TDM2 and MASLD.

Background: In the presence of obesity, high bone mineral density (BMD) seems not to protect against fragility fractures at selected body sites. The aim of this study was to compare femoral BMD in hip- fracture women with versus without obesity.

Methods: At a median of 19 days after an original hip fracture due to fragility we measured BMD by dual-energy X-ray absorptiometry at the non-fractured femur. Densitometric osteoporosis was diagnosed with a T-score <-2.5. Obesity was defined with a Body Mass Index ≥30 kg/m².

Results: We studied 674 women. Mean T-scores were significantly higher in the 55 women with obesity than in the 619 without obesity, with a between-group difference of 0.79 (95% CI from 0.53 to 1.05, P<0.001). Adjustments for age, type of hip fracture, concomitant neurologic impairment, 25-hydroxyvitamin D, parathyroid hormone and estimated glomerular filtration rate did not erase the significant association between obesity and high T-scores (P<0.001). A woman without obesity had an adjusted odds ratio of 2.7 (95% CI from 1.4 to 5.2, P=0.002) for having densitometric osteoporosis compared to a woman with obesity.

Conclusions: BMD was higher in the hip-fracture women with versus without obesity. High BMD levels may not protect obese women against hip fractures and may falsely reassure patients and clinicians. To avoid underestimation of hip-fracture risk due to high BMD, we suggest an adjustment of risk calculation based on the 0.79 T-score difference between hip-fracture women with and without obesity. Adjustment validation by robust prospective studies is needed.

Background: A uniform definition distinguishing metabolically healthy obesity (MHO) from metabolically unhealthy obesity (MUO) is lacking. MUO is characterized by higher liver and visceral fat than MHO. Epicardial fat tissue (EFT) is an index of cardiac adiposity strongly associated with risk of cardiovascular events. This study aimed to further define the MHO/MUO status by evaluating EFT and hepatic steatosis/fibrosis indices in adults presenting visceral obesity.

Methods: In this monocentric, observational study, 56 patients (48 females; 43.8±13.1 years) were recruited. Clinical characteristics, anthropometric measurements, and metabolic parameters were evaluated. Hepatic fibrosis and steatosis were assessed by Fibroscan (502Touch, Echosense). EFT thickness was assessed by transthoracic echocardiography (GE Vivid E95 system). EFT thickness values of 9.5 mm in men and 7.5 mm in women were used as predictors of the metabolic syndrome (MetS).

Results: Patients with MUO had significantly higher steatosis/fibrosis indices and EFT values than the MHO group (P<0.001). EFT values above the cut-off were found in 82.1% of MUO, but also in 42.9% of MHO. At ROC analysis, the specificity and sensitivity of the EFT cut-off point to predict MUO phenotype combined with hypertension, 60-min post load plasma glucose, and adiponectin, were 98.6% and 92.0%, respectively.

Conclusions: As EFT thickness values above the predictive threshold for MetS were found in about half of MHO, the MHO/MUO classification may not correctly identify the cardiovascular risk of MHO. Further clinical evidence is needed to confirm EFT thickness as potential additional marker for MHO/MUO phenotypic differentiation.