Expert Review of Endocrinology & Metabolism最新文献

Introduction: Diabetes mellitus (DM) and the 2019 coronavirus (COVID-19) appear to interact in both directions. There is mounting proof that patients with DM have a worse COVID-19 prognosis than those without it. Pharmacotherapy is also known to affect in view of the possible interplay between drugs and the pathophysiology of the above conditions in a given patient.

Areas covered: In this review, we discuss the pathogenesis of COVID-19 and its connections with diabetes mellitus. We also analyze the treatment modalities for COVID-19 and diabetes patients. The possible mechanisms of the different medications and their management limitations are also systematically reviewed.

Expert opinion: COVID-19 management as well as its knowledge base is changing constantly. The Pharmacotherapy and the choice of drugs also need to be specifically considered in view of the concomitant presence of these conditions in a patient. Anti-diabetic agents must be carefully evaluated in diabetic patients in view of the disease's severity, blood glucose level, appropriate treatment, and other components that could aggravate adverse events. A methodical technique is anticipated to enable the safe and rational use of drug therapy in COVID-19-positive diabetic patients to take.

Introduction: Testosterone concentrations in men decline with advancing age, with low testosterone concentrations being associated with multiple morbidities, an increased risk of early mortality, and a reduced quality of life. The purpose of this study was to examine the effects of alcohol on testosterone synthesis in men by investigating its effects on each level of the hypothalamic-pituitary-gonadal axis.

Areas covered: Acute consumption of a low-to-moderate amount of alcohol increases testosterone concentrations in men, while consumption of a large volume of alcohol is associated with a reduction in serum testosterone concentrations. Elevated testosterone concentrations result from the increased activity of detoxification enzymes in the liver. Conversely, the primary mechanisms of action involved in the reduction of testosterone are increased hypothalamic-pituitary-adrenal axis activity, inflammation, and oxidative stress. When alcohol is consumed in excess, particularly chronically, it negatively affects testosterone production in men.

Expert opinion: Since testosterone is an important component of men's health and wellbeing, current levels of alcohol consumption in many countries of the world require urgent attention. Elucidating the relationship between alcohol consumption and testosterone may be useful in identifying strategies to attenuate the testosterone-reducing effects of excessive or chronic alcohol consumption.

Introduction: The COVID-19 pandemic has changed the landscape of modern medicine on a global scale. An emerging concern is the recognition of a bidirectional relationship between COVID-19 and diabetes. Diabetes is a risk factor for severe COVID-19 illness. Intriguingly, recent epidemiological and in vitro studies suggest that infection with SARS-CoV-2, the causative viral agent of COVID-19, is associated with new-onset diabetes and worsening diabetes control. These factors have affected the management of diabetes.

Areas covered: This review provides an overview of our current understanding of the incidence and prevalence of diabetes in relation to the COVID-19 pandemic, highlights studies evaluating SARS-CoV-2's beta cell tropism and its effects on insulin secretion and sensitivity and evaluates the impact of the pandemic on diabetes management and metabolic control.

Expert opinion: Epidemiological studies have noted an increase in the incidence of new-onset diabetes associated with COVID-19 in patients with phenotypes of type 1 diabetes, type 2 diabetes and Ketosis-Prone Diabetes. Prospective studies are needed to fully elucidate the association between COVID-19 and diabetes and to characterize persons at risk of developing diabetes after SARS-CoV-2 infection, identify those who should be screened for diabetes, and determine the natural histories of different forms of diabetes associated with COVID-19.

Introduction: The pathogenic role of deregulated histone (de-)acetylation by histone deacetyles (HDACs) has been demonstrated in several human cancers. While some HDAC inhibitors (HDACi) have been approved for individual entities, for endocrine tumors such translation into clinical practice has not yet been achieved.

Areas covered: Relevant results identified by structured searches in PubMed as well as in reference lists are summarized in a narrative review to discuss the current knowledge of HDAC involvement and their therapeutic relevance in endocrine tumors. For thyroid, neuroendocrine, and adrenal tumors, various oncogenic mechanisms of HDAC deregulation and effects of HDAC inhibitors (HDACi) have been identified in preclinical studies including direct cancer cell toxicity and modification of differentiation status.

Expert opinion: Based on positive pre-clinical results, the research on HDAC (inhibition) in the various endocrine tumors should be intensified - yet, it needs to be considered that i) HDACs' oncogenic actions might constitute only a part of epigenetic mechanisms driving cancer, ii) individual HDAC has different roles in different endocrine tumor entities, iii) inhibition of HDACs might be especially attractive in combination with conventional or other targeted therapies, and iv) new HDAC-inhibiting drugs with improved specificity or functionally modified HDACi might further improve their efficacy.

Introduction: The most significant articles on diabetes pharmacotherapy and technology in the peer-reviewed literature from 2020, as determined by a panel of pharmacists with expertise in diabetes care and education, are summarized.

Areas covered: Members of the Association of Diabetes Care and Education Specialists Pharmacy Community of Interest were selected to review articles published in prominent peer-reviewed journals in 2020 that most impacted diabetes pharmacotherapy and technology. A list of 37 nominated articles were compiled (22 in diabetes pharmacotherapy and 15 in diabetes technology). Based on discussion among the authors, the articles were ranked based on significant contribution, impact, and diversity to diabetes pharmacotherapy and technology. The top 10 highest ranked publications (n = 6 for diabetes pharmacotherapy and n = 4 in diabetes technology) are summarized in this article.

Expert opinion: With the significant number of publications in diabetes care and education, it can be challenging and overwhelming to remain current with published literature. This review article may be helpful in identifying key articles in diabetes pharmacotherapy and technology from the year 2020.

Introduction: Pituitary adenomas can show a tendency to grow, despite multimodal treatment. Temozolomide (TMZ) has been used in the last 15 years in patients with aggressive pituitary tumors. TMZ requires a careful balance of different expertise, especially for selection criteria.

Areas covered: We conducted: (1) a systematic review of the published literature from 2006 to 2022, collecting only cases with a complete description of patient follow-up after TMZ discontinuation; (2) a description of all patients with aggressive pituitary adenoma or carcinoma treated in Padua (Italy).

Expert opinion: There is considerable heterogeneity in the literature: TMZ cycles duration ranged from 3 to 47 months; the follow-up time after TMZ discontinuation ranged from 4 to 91 months (mean 24 months, median 18 months), at least a stable disease has been reported in 75% of patients after a mean 13 months (range 3-47 months, median 10 months). The Padua (Italy) cohort reflects the literature. Future directions to explore are to understand the pathophysiological mechanism of TMZ resistance escape, to develop predicting factors to TMZ treatment (especially through the delineation of the underlying transformation processes), and to further expand the therapeutic applications of TMZ (as neoadjuvant, combined with radiotherapy).

Objective: Hyperphagia and early-onset, severe obesity are clinical characteristics of rare melanocortin-4 receptor (MC4R) pathway diseases due to loss-of-function (LOF) variants in genes comprising the MC4R pathway. In vitro functional characterization of 12,879 possible exonic missense variants from single-nucleotide variants (SNVs) of LEPR, POMC, and PCSK1 was performed to determine the impact of these variants on protein function.

Methods: SNVs of the three genes were transiently transfected into cell lines, and each variant was subsequently classified according to functional impact. We validated three assays by comparing classifications against functional characterization of 29 previously published variants.

Results: Our results significantly correlated with previously published pathogenic categories (r = 0.623; P = 3.03 × 10^-4) of all potential missense variants arising from SNVs. Of all observed variants identified through available databases and a tested cohort of 16,061 patients with obesity, 8.6% of LEPR, 63.2% of PCSK1, and 10.6% of POMC variants exhibited LOF, including variants currently classified as a variant of uncertain significance (VUS).

Conclusions: The functional data provided here can assist in the reclassification of several VUS in LEPR, PCSK1, and POMC and highlight their impact in MC4R pathway diseases.