Minerva endocrinology最新文献

Background: Prenatal exposure to dioxin, a known endocrine disruptor, after the Seveso accident of 1976 has been associated with thyroid dysfunction, metabolic syndrome and semen quality reduction. Experimental exposure to dioxin in utero produced epigenetic endocrine modifications associated with reduction of semen quality, while in men epigenetic effects are not known. Our objective was to study, by a case control approach, the long-term epigenetic effects of prenatal dioxin exposure in 38 men whose mothers had been exposed to high doses of dioxin, serum median 52.0 ppt at exposure, and therefore who were exposed in utero, median 24.7 ppt at pregnancy, vs. 41 unexposed men.

Methods: Bisulfite-converted DNA was hybridized onto illumina Infinium Methylation EPIC BeadChip and methylation differences were studied at both individual probe (DMPs) and gene region (DMRs) levels.

Results: We identified hypomethylation of the SPAG1 gene region and a slightly hypermethylated region containing genes of the HOXA family associated with thyroid and skeletal development. An elevated level of epigenetic drift was noted in the exposed group potentially contributing to disease risk. Epigenetic age acceleration did not show significant association with in-utero dioxin exposure. Additionally, we found heightened neutrophils and diminished natural killer cells in blood of dioxin exposed men.

Conclusions: These observations are the first in the literature and align with the long-term semen quality reduction and alteration of thyroid homeostasic mechanisms reported in children exposed in utero to dioxin in Seveso. The actual dioxin background serum levels, 1.0-2.0 ppt, are much lower than those associated to these effects.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreatic islets, resulting in complete insulin deficiency. The pathogenesis of T1D is multifactorial and includes genetic predisposition and environmental triggers. Recent research has highlighted the role of microRNAs (miRNAs) in regulating immune responses and β-cell function, making them promising biomarkers and therapeutic targets. Our research included published articles focused on MiRNAs are small, non-coding RNA molecules that modulate gene expression post-transcriptionally, influencing processes such as cell proliferation, differentiation and apoptosis. Data was gathered from different sources including different databases. This review examines the biogenesis and function of miRNAs, their involvement in T1D pathogenesis, and their potential role as therapeutic targets. Also addressing the challenges and future directions for miRNA-based therapies. In T1D, miRNAs have been shown to regulate immune-mediated β-cell destruction and inflammatory responses, contributing to disease progression. miR-21, miR-146a, and miR-155 play important roles in modulating immune pathways that influence β-cell survival. Due to their potential for early diagnosis and therapeutic modulation, miRNAs are being explored as non-invasive biomarkers detectable in blood and urine and targets for therapeutic interventions. However, challenges related to the specificity of the miRNA targeting, stability, and delivery systems must be addressed to realize their clinical potential. Nanoparticle-based delivery systems promise to overcome these challenges by increasing the precision of miRNA targeting and improving their stability.

Insulin resistance (IR) is a condition where insulin-targeted tissues (muscle, liver, and adipose tissue) fail to normally respond to insulin action, leading to impaired insulin signaling and hyperglycemia. It is common in individuals with obesity and diagnosed with type 2 diabetes mellitus (T2DM), with the most prevalent disorders being polycystic ovarian syndrome and coronary artery disease. IR is also associated with cardiovascular risk factors such as hypertension and dyslipidemia. Current methods for detecting and measuring insulin sensitivity include the oral glucose tolerance test, insulin tolerance test, hyperinsulinemic-euglycemic clamp. Therapies for treating and preventing IR includes physical activity, diet modifications, and medications like Glucagon-like peptide-1 receptor agonists, gliclazide and metformin. This review aims at deciphering the molecular mechanisms and factors contributing to IR, potential clinical practices for measuring IR, medications for treating T2DM and the physical activity and dietary measures for controlling IR.

Background: Papillary thyroid carcinoma (PTC) has classically been considered a sporadic carcinoma. However, a subgroup with familial clustering has been observed, which appears to present a poorer prognosis than the sporadic form. The aim of this study is to analyze the recurrence rates and prognostic factors for familial PTC (FPTC) treated with curative intent.

Methods: Multicenter national study, endorsed by the Spanish Association of Surgeons.

Study population: patients with FPTC (families who have at least 2 first-degree relatives with a confirmed PTC) who meet cure criteria after the treatment. Study endpoints: recurrence rate and risk factors for recurrence.

Statistical analysis: Cox regression analysis and survival analysis.

Results: The study included 252 cases with a mean follow-up of 90±68,9 months, recurrence in 26.9% (N.=68) and a disease-free survival of 183,46±7,8 months. In the multivariate analysis, the independent factors for the risk of recurrence were: 1) the number of patients with FPTC in the family (OR 1.165); 2) the multifocality (OR 2.525); 3) the vascular invasion (OR 2.770); and 4) TNM staging system (OR 5.128). In the reanalysis that included the American Thyroid Association (ATA) risk of recurrence, this variable was highly predictive of recurrence (OR 12.048).

Conclusions: FPTC presents a high recurrence rate, which is related to the number of cases of FPTC in the family, the presence of multifocality and vascular invasion, the TNM staging system and the ATA recurrence risk assessment.

Currently, worldwide millions of individuals, athletes, and non-athletes, of different ages and probably of all social genders (cisgender males and females, male to female (MtF) and female to male (FtM) transgenders, etc.), are current or former androgenic anabolic steroids (AAS) abusers. AAS abuse is associated with seriously increased short- and long-term risks for general, reproductive and sexual health. Indeed, to improve the knowledge and health of the population at risk of AAS misuse and standardize the current clinical practice concerning the health risks of such abuse, it is essential to also prevent, detect, diagnose, and treat all reproductive and sexual sequelae of non-therapeutic AAS assumption. The main AAS-related pathways and factors influencing reproduction and sexuality in humans, the possible reproductive and sexual signs and symptoms associated with AAS abuse and to AAS withdrawal, and the major concerns in the diagnosis and management of such clinical conditions are reported. The scientific literature has mainly evaluated male AAS abusers, but, we tried to describe/hypothesize all the possible reproductive and sexual side effects and concerns of AAS abuse also in other genders.

Background: Ageing leads to an increase in the incidence of chronic diseases, including chronic kidney disease (CKD). The increasing proportion of elderly people with reduced renal function draws attention to a sub-population of patients for whom an alternative approach to traditional pharmacological and dietary treatment may be needed. The low-protein diet (LPD) in subjects with CKD helps control complications and may contribute to slowing the progression of the disease. In the follow-up during the conservative phase, nutritional status and the LPD are key points. Of interest, ketoanalogues (KAs) in combination with a LPD significantly reduces the progression to end-stage kidney disease. The aim of this pilot study is to determine the impact at 12 months of LPD supplemented with essential amino acids (EAA) and KAs in a population of 21 over-90-year-olds with advanced CKD in the conservative phase.

Methods: The protein intake of the LPD was 0.6 g/kg body weight/day. Anthropometric measurements and biochemical parameters were monitored at baseline and after 12 months of dietary intervention. The Kidney Failure Risk Equation (KFRE) was used to predict the risk of end stage renal disease.

Results: Significant change in GFR (from 18.04±1.31 to 24.30±2.09 mL/min, P<0.001), azotemia (from 122.38±19.16 to 70.19±15.00 mg/dL, P<0.001) and KFRE score at 2 years (from 33.67±3.88 to 15.09±3.03%, P<0.001) and at 5 years (from 71.94±5.13 to 39.76±6.60% at 5 years, P<0.001). Laboratory parameters (azotemia, albumin, total protein, total cholesterol, transferrin, Hb, PTH, HbA1c, TSAT, CRP) improved. Two patients were hospitalized during the observation period, no cardiovascular events or deaths were reported.

Conclusions: LPD supplemented with EAA and KAs has proven to be a safe and effective tool in the conservative treatment of the over-aged with advanced CKD. Dietary treatment improves renal function and management of complications, reducing the risk of terminal uremia and initiation of replacement treatment by not exposing patients to the risk of malnutrition.

Introduction: Metabolic surgery is the best choice of treatment for patients with overweight; however, choosing an appropriate method remains a challenge for bariatric surgeons.

Evidence acquisition: Based on a literature search in the PubMed database, long-term metabolic and weight loss outcomes of standard care (SC) and different metabolic interventions were collected. Descriptive statistics, initial direct pairwise comparisons using the Ivhet-method and a network meta-analysis (General Pairwise Modelling) on change in Body Mass Index (BMI) and a cost-utility analysis based on the Markov model were performed.

Evidence synthesis: Analysis of the PubMed database identified 1324 unique publications. After rigorous screening, relevant publications were retrieved and 22 studies were enrolled, including a total of 12695 cases. Long-term effectiveness was unsatisfactory after SC. Surgical patients achieved good rates of resolution of comorbidities. All surgical procedures had over 25% of total weight loss (TWL%) and over 60% of excess weight loss (EWL%) at 5 years. Deterministic cost-effectiveness analysis showed the superiority of one-anastomosis gastric bypass (OAGB) (effectiveness: 4.145, cost: €22,484). Sensitivity analysis presented the absolute and relative (to SC) benefit of OAGB. Simple direct pairwise comparisons could not prove the superiority of any treatment modality; however, network meta-analysis in combination with cost-utility analysis showed OAGB to be the most efficient method (OR was 1.36, 1.24 and 1.08 for OAGB, LRYGB and LSG compared to SC, respectively).

Conclusions: Metabolic surgery seems to be a more favourable approach in weight loss management than standard treatment; however, our analysis could not prove the superiority of any kind of surgery.

Background: Covering a significant part of a woman's life, the postmenopausal phase is often associated with the onset of obesity, metabolic dysfunction, osteoporosis, and their most disabling complications. In this context, scant evidence from both preclinical and clinical studies suggests that single nucleotide polymorphisms (SNPs) of the follicle-stimulating hormone receptor (FSHR) gene might be involved in the etiopathogenesis of these conditions, posing them as possible molecular predictors of their development. Therefore, this study aimed to evaluate the role of the FSHR gene SNPs c.2039A>G and c.-29 G>A on Body Mass Index (BMI), metabolic parameters, and bone metabolism in postmenopausal women.

Methods: To achieve this goal, 49 postmenopausal Caucasian women aged from 45 to 80 years and with no factors known to influence metabolism and/or bone mineral density (BMD) were enrolled and assessed for their medical history, medical family history, anthropometric parameters and hormonal, metabolic and lipid profiles, and BMD. Then, they were genotyped for the FSHR gene SNPs c.2039A>G and c.-29G>A. Finally, the resulting data were classified according to woman's genotypes and subjected to statistical analysis.

Results: No significant differences were found between the distributions of most endpoint parameters examined by genotype. However, none of the women with the c.2039A>G FSHR GG gene SNP were affected by obesity and had the highest lumbar BMD z-score within the cohort. Additionally, those with the FSHR c.-29G>A AA genotype had the lowest serum glucose levels.

Conclusions: This preliminary study suggests that the FSHR c.2039A>G GG SNP, which is associated with reduced sensitivity of the FSHR, may have a protective role against obesity, offering further evidence for the possible association among FSH, FSHR polymorphisms, and insulin metabolism.