COVID-19 and endocrine diseases. A statement from the European Society of Endocrinology

ESE has issued a statement about the role and responsibilities of endocrinologists worldwide during the current COVID-19 outbreak, prepared by Manuel Puig-Domingo, Mónica Marazuela and Andrea Giustina also includes a ‘decalogue’ for endocrinologists in midst of the COVID-19 pandemic. This statement is the "draft" document for the Springer articl

Epithelial-Mesenchymal Transition in the Resistance to Somatostatin Receptor Ligands in Acromegaly

Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory and invasive capacities. EMT is involved in physiological processes, such as embryogenesis and wound healing, and in pathological processes such as cancer, playing a pivotal role in tumor progression and metastasis. Pituitary tumors, although typically benign, can be locally invasive. Different studies have shown the association of EMT with increased tumor size and invasion in pituitary tumors, and in particular with a poor response to Somatostatin Receptor Ligands (SRLs) treatment in GH-producing pituitary tumors, the main cause of acromegaly. This review will summarize the current knowledge regarding EMT and SRLs resistance in acromegaly and, based on this relation, will suggest new biomarkers and possible therapies to SRLs resistant tumors

Lipid Metabolism and Epigenetics Crosstalk in Prostate Cancer

Prostate cancer (PCa) is the most commonly diagnosed malignant neoplasm in men in the Western world. Localized low-risk PCa has an excellent prognosis thanks to effective local treatments; however, despite the incorporation of new therapeutic strategies, metastatic PCa remains incurable mainly due to disease heterogeneity and the development of resistance to therapy. The mechanisms underlying PCa progression and therapy resistance are multiple and include metabolic reprogramming, especially in relation to lipid metabolism, as well as epigenetic remodelling, both of which enable cancer cells to adapt to dynamic changes in the tumour. Interestingly, metabolism and epigenetics are interconnected. Metabolism can regulate epigenetics through the direct influence of metabolites on epigenetic processes, while epigenetics can control metabolism by directly or indirectly regulating the expression of metabolic genes. Moreover, epidemiological studies suggest an association between a high-fat diet, which can alter the availability of metabolites, and PCa progression. Here, we review the alterations of lipid metabolism and epigenetics in PCa, before focusing on the mechanisms that connect them. We also discuss the influence of diet in this scenario. This information may help to identify prognostic and predictive biomarkers as well as targetable vulnerabilities

Development of a new tool for assessing Health-Related Quality of Life in patients with primary hyperparathyroidism

Background: Several studies in recent years have evaluated Health Related Quality of Life (HRQoL) of patients with primary hyperparathyroidism (PHPT). No disease specific questionnaires are available to assess the impact of the disease. The aim of this research is to describe the development of a new disease specific Quality of Life (QoL) questionnaire for use specifically with PHPT patients. Methods: A conceptual model was developed describing the impact of the disease and its symptoms on QoL domains. A literature review was conducted to identify the most relevant domains. A focus group with experts was used to validate the domains; 24 patients were also interviewed to complement the information from the patient's perspective. A content analysis of the interviews was performed to identify items related with the impact of the disease, leading to PHPQoL-V.1 which was presented to a sample of 67 patients. Reliability was assessed by Cronbach's coefficient alpha and item-total score correlations. Validity was assessed by a factor analysis performed to determine the number of domains. Rasch analysis was carried out in order to refine the questionnaire items. Results: 259 items were extracted from the interviews that were subsequently reduced to 34 items. Cronbach's coefficient alpha was 0.92. The factor analysis extracted two domains (physical and emotional). After Rasch analysis the questionnaire PHPQoL-V.2 kept 16 items (9 physical and 7 emotional). The questionnaire was developed in a Spanish population and the final version was translated to English through translation and back-translation. Conclusion: The first disease specific HRQoL questionnaire for PHPT patients (PHPQoL-16) has been developed. Validation studies designed to assess measurement properties of this tool are currently underway

Microbiota, Fiber, and NAFLD : Is There Any Connection?

Gut microbiota can contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD). In fact, some specific changes of gut microbiota are observed in patients in what is called dysbiota. There has been a lot of investigation by using a variety of interventions, including diet, showing the possibility to modify components of gastrointestinal dysbiota towards healthy and multivariate microbiota to restore physiologic status. One of the main focuses has been dietary fiber (DF), in which most of its variants are prebiotics. The highest effective treatment for NAFLD is, so far, weight loss achieved by caloric restriction. DF supplementation with oligofructose facilitates weight loss, enhances the production of beneficial metabolites, decreases some pathogenic bacteria population by increasing Bifidobacteria, and has effects on intestinal barrier permeability. DF use has been associated with improvement in diverse metabolic diseases, including NAFLD, by modifying gut microbiota. Additionally, it has been shown that a higher insoluble fiber consumption (≥7.5 g/day) revealed improvements in 3 different scores of liver fibrosis. Further research is needed, but given the evidence available, it is reasonable to prescribe its consumption in early stages of NAFLD in order to prevent disease progression

Nutritional Status According to the GLIM Criteria in Patients with Chronic Heart Failure : association with Prognosis

Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria were recently proposed to build a global consensus on the diagnostic criteria for malnutrition. This study aimed to evaluate the GLIM criteria for its prognostic significance in outpatients with heart failure (HF), and to compare them to a previous validated method, such as the Mini Nutritional Assessment (MNA). Methods: This was a post hoc observational analysis of a prospectively recruited cohort, which included 151 subjects that attended an outpatient HF clinic. At baseline, all patients completed the nutritional screening MNA short form and the nutritional assessment MNA. In a post hoc analysis, we evaluated the GLIM criteria at baseline. The outcomes were based on data from a five-year follow-up. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular (CV) mortality and recurrent HF-related hospitalizations. We also investigated whether the GLIM criteria had better prognostic power than the MNA. Results: Abnormal nutritional status was identified in 19.8% of the patients with the GLIM criteria and in 25.1% with the MNA. In the multivariate analyses (age, sex, NYHA functional class, diabetes, and Barthel index), nutritional status assessed by the MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalizations during the five-year follow-up. Conclusions: Malnutrition assessed by MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalization in our cohort of outpatients with HF

Thyroid Hormone Upregulates Zinc-α-glycoprotein Production in the Liver but Not in Adipose Tissue

Overproduction of zinc-α-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α-glycoprotein expression in adipose tissue could be the reason why zinc-α-glycoprotein is not related to weight loss in hyperthyroidism

Prenatal Betamethasone Exposure and its Impact on Pediatric Type 1 Diabetes Mellitus : A Preliminary Study in a Spanish Cohort

Betamethasone, a glucocorticoid used to induce lung maturation when there is a risk of preterm delivery, can affect the immune system maturation and type 1 diabetes (T1D) incidence in the progeny. It has been described that prenatal betamethasone protects offspring from experimental T1D development. The main aim of this study was to evaluate the possible association between betamethasone prenatal exposure and T1D in humans. Research Design and Methods. A retrospective case-control study with a total of 945 children, including 471 patients with T1D and 474 healthy siblings, was performed. Participants were volunteers from the Germans Trias i Pujol Hospital and DiabetesCero Foundation. Parents of children enrolled in the study completed a questionnaire that included questions about weeks of gestation, preterm delivery risk, weight at birth, and prenatal betamethasone exposure of their children. Multiple logistic regression was used to detect the association between betamethasone exposure and T1D. We compared T1D prevalence between subjects prenatally exposed or unexposed to betamethasone. The percent of children with T1D in the exposed group was 37.5% (21 of 56), and in the unexposed group was 49.52% (410 of 828) (p = 0.139). The percentage of betamethasone-treated subjects with T1D in the preterm group (18.05%, 13 of 72) was significantly higher than that found in the control group (12.5%, 9 of 72) (p = 0.003). The odds ratio for T1D associated with betamethasone in the univariate logistic regression was 0.59 (95% confidence interval, 0.33; 1.03 [ p = 0.062]) and in the multivariate logistic regression was 0.83 (95% confidence interval, 0.45; 1.52 [ p = 0.389]). The results demonstrate that the prenatal exposure to betamethasone does not increase T1D susceptibility, and may even be associated with a trend towards decreased risk of developing the disease. These preliminary findings require further prospective studies with clinical data to confirm betamethasone exposure effect on T1D risk