Expert Review of Endocrinology & Metabolism最新文献

Introduction: Known for its effect on labor and lactation and on emotional and social functions, oxytocin has recently emerged as a key modulator of feeding behavior and indeed suggested as a potential treatment for obesity. The potential positive effect of oxytocin on both metabolic and psychological-behavioral complications of hypothalamic lesions makes it a promising tool in the management of these conditions.

Areas covered: The aim of the present review article is to provide an overview of the mechanism of action and clinical experience of the use of oxytocin in different forms of obesity.

Expert opinion: Current evidence suggests a potential role of oxytocin in the treatment of obesity with different causes. Several challenges remain: an improved understanding of the physiological regulation, mechanisms of action of oxytocin, and interplay with other endocrine axes is fundamental to clarify its role. Further clinical trials are needed to determine the safety and efficacy of oxytocin for the treatment of different forms of obesity. Understanding the mechanism(s) of action of oxytocin on body weight regulation might also improve our understanding of obesity and reveal possible new therapeutic targets - as well as promoting advances in other fields in which oxytocin might be used.

Introduction: Immune-checkpoint inhibitor therapy modulates the response of the immune system acting against cancer. Two pathways impacted by this kind of treatment are the CTLA4 and the PD-1/PD-L1 pathways. ICI therapy can trigger autoimmune adverse effects, known as immune-related Adverse Events (irAEs).

Areas covered: This review focuses on irAEs which affect the endocrine system. This review elucidates the pathways used by these drugs with a focus on the hypothetical pathogenesis at their basis. In fact, the pathophysiology of irAEs concerns the possibility of an interaction between cellular autoimmunity, humoral immunity, cytokines, chemokines, and genetics. The endocrine irAEs examined are thyroid dysfunctions, immune related-hypophysitis, diabetes, peripheral adrenal insufficiency, and hypoparathyroidism.

Expert opinion: There is still much to investigate in endocrine irAES of checkpoint inhibitors. In the future, checkpoint inhibitors will be increasingly utilized therapies, and therefore it is crucial to find the proper diagnostic-therapeutic program for irAEs, especially as endocrine irAEs are nonreversible and require lifelong replacement therapies.

Introduction: Patients undergoing surgery require a thorough assessment preoperatively. Hyperglycemia is associated with poor outcomes, and stability of glucose levels is an important factor in preoperative management. Diabetes presents a particular challenge since patients are often on multiple medications encompassing glycemic management and cardiovascular therapies.

Areas covered: A PubMed search of published data and reviews on preoperative approaches in diabetes was conducted. Consensus opinion drives most of the guidelines and recommendations for management of diabetes in surgical patients. Pathophysiology is often complex with varying levels of glucose and surgical stress. Establishing well-controlled diabetes prior to surgical intervention should be standard practice in non-emergent procedures. We review the best practices for implementing preoperative assessment, with diabetes with a focus on diabetes medications.

Expert opinion: The management of a patient preoperatively varies by region and country. Institutions differ in approaches to preoperative evaluation and the establishment of consistent approaches would provide a platform for monitoring patient outcomes. Multidisciplinary teams and pre-assessment clinics for preoperative evaluation can enhance patient care for those undergoing surgery.

Introduction: Sarcopenic obesity (SarcO) is defined as the confluence of reduced muscle mass and function and excess body fat. The scientific community is increasingly recognizing this syndrome, which affects a subgroup of persons across their lifespans and places them at synergistically higher risk of significant medical comorbidity and disability than either sarcopenia or obesity alone. Joint efforts in clinical and research settings are imperative to better understand this syndrome and drive the development of urgently needed future interventions.

Areas covered: Herein, we describe the ongoing challenges in defining sarcopenic obesity and the current state of the science regarding its epidemiology and relationship with adverse events. The field has demonstrated an emergence of data over the past decade which we will summarize in this article. While the etiology of sarcopenic obesity is complex, we present data on the underlying pathophysiological mechanisms that are hypothesized to promote its development, including age-related changes in body composition, hormonal changes, chronic inflammation, and genetic predisposition.

Expert opinion: We describe emerging areas of future research that will likely be needed to advance this nascent field, including changes in clinical infrastructure, an enhanced understanding of the lifecourse, and potential treatments.

Introduction: Melatonin, originally isolated from the mammalian pineal gland, was subsequently identified in many animal cell types and in plants. While melatonin was discovered to inhibit cancer more than 5 decades ago, its anti-cancer potential has not been fully exploited despite its lack of serious toxicity over a very wide dose range, high safety margin, and its efficacy.

Areas covered: This review elucidates the potential mechanisms by which melatonin interferes with tumor growth and metastasis, including its ability to alter tumor cell metabolism, inhibit epithelial-mesenchymal transition, reverse cancer chemoresistance, function synergistically with conventional cancer-inhibiting drugs while limiting many of their side effects. In contrast to its function as a potent antioxidant in normal cells, it may induce oxidative stress in cancer cells, contributing to its oncostatic actions.

Expert opinion: Considering the large amount of experimental data supporting melatonin's multiple and varied inhibitory effects on numerous cancer types, coupled with the virtual lack of toxicity of this molecule, it has not been thoroughly tested as an anti-cancer agent in clinical trials. There seems to be significant resistance to such investigations, possibly because melatonin is inexpensive and non-patentable, and as a result there would be limited financial gain for its use.

Introduction: Neuroendocrine tumors (NETs) are a diverse group of tumors with origins from different primary sites such as gastro-entero-pancreatic, lung and endocrine tissue. Worldwide, their incidence has increased in recent decades. Advances in imaging and better clinical awareness are traditionally attributed to this trend; however, other factors such as genetic and environmental contributors are appreciated as well.

Areas covered: The purpose of this article is to review the worldwide epidemiologic trends in incidence of NET through the decades and discuss the various factors potentially contributing to the observed changes in incidence trends.

Expert opinion: Overall, the incidence of NET has increased across the globe over the last few decades. Although multiple genetics and environmental factors have been proposed, the majority of this increase in incidence is secondary to earlier detection. Future studies will help in more accurate assessments and an improved understanding of disease incidence among patients with different grades and differentiation.

Introduction: Disorders of Sex Development (DSD) associated with adrenal dysfunction occur due to different defects in the proteins involved in gonadal and adrenal steroidogenesis.

Areas covered: The deficiencies in 21-hydroxylase and 11β-hydroxylase lead to DSD in 46,XX patients, defects in StAR, P450scc, 17α-hydroxylase and 17,20-lyase lead to 46,XY DSD, and 3β-HSD2 and POR deficiencies cause both 46,XX and 46,XY DSD. Challenges in diagnosis arise from the low prevalence and the variability in serum steroid profiles. Replacement therapy with hydrocortisone and fludrocortisone helps to minimize life-threatening adrenal crises; however, availability is still an unresolved problem in many countries. Adverse health outcomes, due to the disease or its treatment, are common and include adult short stature, hypertension, osteoporosis, obesity, cardiometabolic risk, and reproductive health issues. Potential biomarkers to improve monitoring and novel treatment options that have been developed with the primary aim to decrease adrenal androgen production are promising tools to help improve the health and quality of life of these patients.

Expert opinion: Steroid profiling by mass spectrometry and next-generation sequencing technologies represent useful tools for establishing an etiologic diagnosis and drive personalized management. Nonetheless, access to health care still remains an issue requiring urgent solutions in many resource-limited settings.

Introduction: In the treatment scenario of PanNETs-targeted therapies are desired but limited, as rarity and heterogeneity on PanNETs pose limitations to their development.

Areas covered: We performed a literature review searching for promising druggable biomarkers and potential treatments to be implemented in the next future. We focused on treatments which have already reached clinical experimentation, although in early phases. Six targets were identified, namely Hsp90, HIFa, HDACs, CDKs, uPAR, and DDR. Even though biological rational is strong, so far reported efficacy outcomes are quite disappointing. The reason of that should be searched in the patients' heterogeneity, lack of biomarker selection, poor knowledge of interfering mechanisms as well as difficulties in patients accrual. Moreover, different ways to assess treatment efficacy should be considered, other than response rate, in light of the more indolent nature of NETs.

Expert opinion: Development of targeted treatments in PanNETs is still an uncovered area, far behind other more frequent cancers. Rarity of NETs led to accrual of unselected populations, possibly jeopardizing the drug efficacy. Better patients' selection, both in terms of topography, grading and biomarkers is crucial and will help understanding which role targeted therapies can really play in these tumors.

Introduction: Bariatric surgery has demonstrated long-term effectiveness in inducing weight loss and improving metabolic parameters for obesity. Single anastomosis duodeno-ileal (SADI) bypass and single anastomosis sleeve-ileal (SASI) bypass have both emerged as new promising bariatric procedures. In this paper, we review the existing literature and compare the outcomes of SADI and SASI bypass procedures in regard to weight loss, complication rate, and improvement of type II diabetes (T2DM). This has not yet been done in the preexisting literature.

Areas covered: We conducted a systematic literature search of electronic databases focusing on weight loss outcomes, rate of complications and remission, or improvement of T2DM and other obesity-related comorbidities. Seventeen studies on SADI and nine studies on SASI were included. Both are similar in terms of surgical technique and have demonstrated fewer complications when compared to other bariatric procedures. Mean preoperative BMI was similar in both study groups: 46.4 kg/m² in SADI and 48.8 kg/m² in SASI. Mean %EWL at 12 months in the SADI group was 74.1% compared to 77.4% in the SASI group. Preoperative severity of T2DM appeared to be higher in the SASI patient group, with a higher preoperative HbA1c and fasting blood glucose levels. T2DM resolution was achieved in a significant proportion of both SADI and SASI patient populations (78.5% in SADI and 89.0% in SASI). Complication rates were comparable for both procedures.

Expert opinion: Both SADI and SASI are effective in inducing weight loss at 12 months, with a low rate of major complications and mortality. From the studies included in this review, the SASI procedure had a higher impact on T2DM resolution compared to SADI.