Graves' Orbitopathy (GO) is the most frequent extrathyroidal manifestation of Graves' disease (GD). Its ultimate cause remains unclear, but it is commonly considered an autoimmune disorder due to self recognition of autoantigens constitutively expressed by orbital fibroblasts (OFs), and thyroid epithelial cells. High dose intravenous glucocorticoids (ivGC) are the most commonly used treatment for moderately severe and active GO. However, based on the complex pathogenesis of GO, a number of factors may have a protective and maybe a therapeutic role. The use of other medications improving the effect of GC may increase the overall effectiveness of the therapy and reduce GC doses, thereby limiting side effects. Recently, a possible protective role of 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, the so-called statins, and perhaps of lowering cholesterol levels, has been proposed. Thus, statins have been reported to be associated with a reduced frequency of GO in GD patients and in recent cross-sectional and retrospective studies a significant correlation was found between the occurrence of GO and both total and LDL-cholesterol in patients with a GD of relatively recent onset, suggesting a role of cholesterol in the development of GO. Moreover, a correlation was found between the GO clinical activity score and total as well as LDL-cholesterol in untreated GO patients, depending on GO duration, indicating a role of cholesterol on GO activity. Therefore, statin treatment may be beneficial for GO. Here we review this subject, which offers new therapeutic perspectives for patients with GO.

Summary: The food system significantly affects the environment through land use, emissions from livestock, deforestation, and food waste. Diet sustainability considers the environmental effects of food production, distribution, and consumption. Animal products emit more greenhouse gases than plant‐based foods, prompting a shift towards plant‐focused diets for reduced emissions. Sustainable diets, like the EAT‐Lancet model, prioritize plant‐based foods, adjusting for regional eating habits. These diets aim to be both environmentally friendly and conducive to human health, addressing concerns like obesity and chronic diseases. Obesity is a major global health challenge, and its complex relationship with food production and consumption patterns calls for sustainable solutions to reduce pressure on ecosystems and promote healthier lifestyles. Tackling obesity requires holistic strategies that address not only individual health but also the broader environmental impacts of food systems. A systematic review examined the link between plant‐based diets and obesity focusing on studies assessing Body Mass Index (BMI) and body fat assessment. Despite limited research, evidence suggests that adherence to a plant‐based diet, particularly a healthy one, is associated with lower obesity rates. More longitudinal and intervention studies are necessary for a stronger consensus on the matter.

Chromogranin A (CgA) is a plasma biomarker widely used in the follow-up of patients with neuroendocrine neoplasms (NENs). However, its accuracy as a tumor biomarker is relatively low because plasma CgA can increase also in patients with other diseases or in subjects treated with proton-pump inhibitors (PPIs), a class of widely-used drugs. In the attempt to identify a more reliable biomarker for NENs, we investigated, by ELISA, the circulating levels of full-length CgA (CgA_1-439) and of various CgA-derived fragments in 17 patients with ileal or pancreatic NENs, 10 healthy controls, and 21 healthy volunteers before and after treatment with PPIs. Patients with ileal or pancreatic NENs showed increased plasma levels of total-CgA and CgA_1-76 fragment (vasostatin-1, VS-1) compared to controls [median (25^th-75^th-percentiles); total-CgA: 1.85 nM (1.01–4.28) vs 0.75 nM (0.52–0.89), p = 0.004; VS-1: 2.76 nM (1.09–7.10) vs 0.29 nM (0.26–0.32), p<0.001, respectively], but not of CgA_1-439 or CgA_1-373 fragment. VS-1 positively correlated with total-CgA (r = 0.65, p<0.001). The Receiver Operating Characteristic area under the curve was 0.9935 for VS-1 and 0.8824 for total-CgA (p = 0.067). Treatment of patients with somatostatin analogues decreased both total-CgA and VS-1. In contrast, administration of PPIs increased the plasma levels of total-CgA, but not of VS-1. These findings suggest that plasma VS-1 is a novel biomarker for ileal and pancreatic NENs. Considering that VS-1 is a well-defined fragment not induced by proton-pump inhibitors, this polypeptide might represent a biomarker for NENs diagnosis and follow-up more accurate and easier to standardize than CgA.

Postpartum depression (PPD) has a major impact on maternal and offspring wellbeing, with multiple possible risk factors: studies on the association of thyroid peroxidase antibody (TPOAb) positivity and thyroid function with PPD provide heterogeneous results. Objective: To study the association of thyroid function and TPOAb positivity with PPD. Design: We assessed the association of TPOAb and thyroid function with PPD in a population-based prospective cohort study and performed a systematic literature review and meta-analysis. Methods: We measured TSH, FT4, and TPOAb between 9-17 weeks gestation. Postpartum depression was assessed with Edinburgh Postpartum Depression Scale at 2 months postpartum and Brief Symptom Inventory at 2, 6, and 36 months postpartum. Additionally, we performed a systematic literature review and meta-analysis assessing this association. Results: In the present study, there was no association of thyroid function with PPD (TSH OR:0.83, 95%CI 0.58-1.19, p=0.32; fT4 OR:0.99, 95%CI 0.95-1.05, p=0.86), or TPOAb positivity with PPD (OR:0.79, 95%CI 0.47-1.33, p=0.37). An impaired thyroidal response to hCG, a surrogate marker for TPOAb positivity, was associated with a lower risk of PPD (P for interaction TSH=0.04, FT4=0.06). Our systematic review and meta-analysis included three articles which were combined with the present study. There was no statistically significant association of TPOAb positivity with PPD (OR:1.93, 95%CI 0.91-4.10, p= 0.08) but results were heterogeneous (I²=79%). Conclusions: There was no significant association of TPOAb positivity, TSH or FT4 with PPD. Our systematic review and meta-analysis revealed high heterogeneity of the current literature. Although TPOAb-positive women should be monitored for postpartum thyroiditis, our findings do not support routinely screening for PPD.

Context: Impaired metabolic flexibility is associated with prediabetes. However, its assessment with reference methods is impractical in routine clinical practice. Objective: This study investigates the relationship between fasting respiratory exchange ratio (RER), measured through indirect calorimetry, and glucose metabolism in individuals with prediabetes. Methods: The study involved 2 cohorts: (1) a cross-sectional cohort of 10 176 individuals to assess the association between fasting RER and glucose metabolism parameters, and (2) a matched longitudinal cohort of 86 patients with impaired fasting glucose, categorized into fat oxidation (RER < 0.775) and glucose oxidation (RER > 0.925) groups, to evaluate the impact of fasting RER on impaired fasting glucose resolution and fasting glucose after a 1-year lifestyle intervention. Results: In the cross-sectional cohort, a higher fasting RER was associated with higher fasting glucose, insulin, and Homeostatic Model Assessment for Insulin Resistance. In the longitudinal cohort, the fat oxidation group showed a greater reduction in fasting glucose (+5.9; 95% CI 1.4, 10; P = .011) and a higher probability of achieving normal fasting glycemia (log(odds ratio) −0.89; 95% CI −1.8, −0.03; P = .046) after the intervention, despite similar weight loss between groups. Conclusion: Our findings suggest that fasting RER, a readily accessible clinical measure, can provide valuable insights into glucose metabolism and impaired fasting glucose resolution. A lower fasting RER, indicative of a greater capacity for fat oxidation, is associated with improved glycemic control after a lifestyle intervention.

Background/Objectives: Metabolic–bariatric surgery (MBS) is a highly effective treatment for severe obesity; however, gender disparities exist in access and postoperative outcomes. Despite men presenting with higher baseline weight and comorbidity burden, they are significantly underrepresented among MBS patients. Existing evidence on gender-specific outcomes remains inconclusive, particularly within Mediterranean populations under updated clinical guidelines. To evaluate gender differences in weight loss outcomes following sleeve gastrectomy in an Italian cohort managed under current multidisciplinary protocols. Methods: A prospective observational study was conducted and a total of 131 patients (109 females, 22 males) underwent sleeve gastrectomy at a single center. Anthropometric and metabolic parameters were assessed at baseline and 12 months postoperatively. Outcomes included absolute weight loss (TWL%), percentage of initial and excess body weight lost (EWL%), and waist circumference. Group comparisons used t-tests (with Welch’s correction if variances were unequal) and regression models adjusted for baseline BMI and age. Results: At 12 months, men achieved significantly greater absolute weight loss than women (−36.6 kg vs. −31.2 kg; p = 0.028), although no significant differences were observed for TWL%, EWL%, or waist circumference reduction. Gender remained a significant predictor of absolute weight loss in multivariate analysis, but not of proportional weight loss. Both genders showed similar rates of achieving clinically significant weight loss thresholds. Conclusions: While men exhibited greater absolute weight loss, relative weight loss outcomes were comparable between sexes. Gender disparity is observed in the utilization of MBS. These findings highlight the importance of equitable surgical access and tailored postoperative care.