Reviews in Endocrine & Metabolic Disorders最新文献

Due to its rarity and non-specific clinical presentation, accurate diagnosis, and optimal therapeutic strategy of medullary thyroid carcinoma (MTC) remain challenging. Molecular imaging provides valuable tools for early disease detection, monitoring treatment response, and guiding personalized therapies. By enabling the visualization of molecular and cellular processes, these techniques contribute to a deeper understanding of disease mechanisms and the development of more effective clinical interventions. Different nuclear imaging techniques have been studied for assessing MTC, and among them, PET/CT utilizing multiple radiotracers has emerged as the most effective imaging method in clinical practice. This review aims to provide a comprehensive summary of the current use of advanced molecular imaging modalities, with a particular focus on PET/CT, for the management of patients with MTC. It aims to guide physicians towards a rationale for the use of molecular imaging also including theranostic approaches and novel therapeutical opportunities. Overall, we emphasize the evolving role of nuclear medicine in MTC. The integration of diagnostics and therapeutics by in vivo molecular imaging represents a major opportunity to personalize treatment for individual patients, with targeted radionuclide therapy being one representative example.

Although the overall prognosis for differentiated thyroid cancer (DTC) is excellent, a subset of patients will experience disease recurrence or may not respond to standard treatments. In recent years, DTC management has become more personalized in order to enhance treatment efficacy and avoid unnecessary interventions.In this context, major guidelines recommend post-surgery staging to assess the risk of disease persistence, recurrence, and mortality. Consequently, risk stratification becomes pivotal in determining the necessity of postoperative adjuvant therapy, which may include radioiodine therapy (RIT), the degree of TSH suppression, additional imaging studies, and the frequency of follow-up.However, the intermediate risk of recurrence is a highly heterogeneous category that encompasses various risk criteria, often combined, resulting in varying degrees of aggressiveness and a recurrence risk ranging from 5 to 20%. Furthermore, there is not enough long-term prognosis data for these patients. Unlike low- and high-risk DTC, the available literature is contradictory, and there is no consensus regarding adjuvant therapy.We aim to provide an overview of intermediate-risk differentiated thyroid cancer, focusing on criteria to consider when deciding on adjuvant therapy in the current context of personalized approach, including molecular analysis to enhance the accuracy of patient management.

Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim of this systematic review and meta-analysis was to synthesize the available evidence on the use of antiresorptive drugs in FD in terms of changes in bone turnover markers (BTMs), bone mineral density (BMD), and reducing pain. Three databases were searched in October 2022, with an update in July 2023. Of the 1037 studies identified, 21 were retained after eligibility assessment. A random-effects model was used to calculate global effect size and the corresponding standard error. Pamidronate and Denosumab were the most reported drugs in a total of 374 patients assessed. The initiation of treatments was accompanied by an average reduction of 40.5% [CI_95% -51.6, -29.3] in the bone resorption parameters, and 22.0% [CI_95% -31.9, -12.1] in the parameters of bone formation after 6-12 months. BMD was increased in both FD lesions and in the unaffected skeleton. Pain was reduced by 32.7% [CI_95% -52.7, -12.6] after 6-12 months of treatment, and by 44.5% [CI_95% -65.3, -23.6] after a mean 41.2 months of follow-up. The variation in pain was highly correlated to variation in bone resorption (R² = 0.08, p < 0.0001) and formation parameters (R² = 0.17, p < 0.0001). This study supports the overall efficacy of antiresorptive therapies in terms of reducing bone remodeling, improving bone density, and pain in FD.

Knowledge of ectopic insulinomas comes from single cases. We performed a systematic review through PubMed, Web of Science, Embase, eLibrary and ScienceDirect of all cases reported in the last four decades. We also describe one unreported patient. From 28 patients with ectopic insulinoma, 78.6% were female and mean age was 55.7 ± 19.2 years. Hypoglycaemia was the first symptom in 85.7% while 14.3% complained of abdominal pain or genital symptoms. Median tumour diameter was 27.5 [15-52.5] mm and it was localised by CT (73.1%), MRI (88.9%), [⁶⁸Ga]Ga-DOTA-exedin-4 PET/CT (100%), ⁶⁸Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC (100%), somatostatin receptor scintigraphy (40%) and endoscopic ultrasound (50%). Ectopic insulinomas were located at duodenum (n = 3), jejunum (n = 2), and one respectively at stomach, liver, appendix, rectum, mesentery, ligament of Treitz, gastrosplenic ligament, hepatoduodenal ligament and splenic hilum. Seven insulinomas were affecting the female reproductive organs: ovary (n = 5), cervix (n = 2) and remaining tumours were at retroperitoneum (n = 3), kidney (n = 2), spleen (n = 1) and pelvis (n = 1). 89.3% underwent surgery (66.7% surgery vs. 33.3% laparoscopy) and 16% underwent an ineffective pancreatectomy. 85.7% had localized disease at diagnosis and 14.3% developed distant metastasis. Median follow-up time was 14.5 [4.5-35.5] months and mortality was reported in 28.6% with median time until death of 60 [5-144] months. In conclusion, ectopic insulinomas are presented as hypoglycaemia with female preponderance. Functional imaging [⁶⁸Ga]Ga-DOTA-exedin-4 PET/CT and ⁶⁸Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC have very high sensitivity. Clinicians should be alert to the possibility of extra-pancreatic insulinomas when classic diagnostic tests and intraoperative pancreas exploration failed to locate the tumour.

The initial step for the differential diagnosis of hypoglycemia is to determine whether it is hyperinsulinemic or non hyperinsulinemic. Existing literature discusses drug-related hypoglycemia, but it misses a focus on drug-induced hyperinsulinemic hypoglycemia (DHH). Here we reviewed the association existing between drugs and hyperinsulinemic hypoglycemia. We primarily selected on the main electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) the reviews on drug-induced hypoglycemia. Among the drugs listed in the reviews, we selected the ones linked to an increase in insulin secretion. For the drugs missing a clear association with insulin secretion, we investigated the putative mechanism underlying hypoglycemia referring to the original papers. Our review provides a list of the most common agents associated with hyperinsulinemic hypoglycemia (HH), in order to facilitate both the recognition and the prevention of DHH. We also collected data about the responsiveness of DHH to diazoxide or octreotide.

Background and aims: Bariatric surgery is the most effective treatment in individuals with obesity to achieve remission of type 2 diabetes. Post-bariatric surgery hypoglycaemia occurs frequently, and management remains suboptimal, because of a poor understanding of the underlying pathophysiology. The glucoregulatory hormone responses to nutrients in individuals with and without post-bariatric surgery hypoglycaemia have not been systematically examined.

Materials and methods: The study protocol was prospectively registered with PROSPERO. PubMed, EMBASE, Web of Science and the Cochrane databases were searched for publications between January 1990 and November 2021 using MeSH terms related to post-bariatric surgery hypoglycaemia. Studies were included if they evaluated individuals with post-bariatric surgery hypoglycaemia and included measurements of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and/or glucagon concentrations following an ingested nutrient load. Glycated haemoglobin (HbA_1c) was also evaluated. A random-effects meta-analysis was performed, and Hedges' g (standardised mean difference) and 95% confidence intervals were reported for all outcomes where sufficient studies were available. The τ² estimate and I² statistic were used as tests for heterogeneity and a funnel plot with the Egger regression-based test was used to evaluate for publication bias.

Results: From 377 identified publications, 12 were included in the analysis. In all 12 studies, the type of bariatric surgery was Roux-en-Y gastric bypass (RYGB). Comparing individuals with and without post-bariatric surgery hypoglycaemia following an ingested nutrient load, the standardised mean difference in peak GLP-1 was 0.57 (95% CI, 0.32, 0.82), peak GIP 0.05 (-0.26, 0.36), peak insulin 0.84 (0.44, 1.23), peak C-peptide 0.69 (0.28, 1.1) and peak glucagon 0.05 (-0.26, 0.36). HbA_1c was less in individuals with hypoglycaemia - 0.40 (-0.67, -0.12). There was no evidence of substantial heterogeneity in any outcome except for peak insulin: τ² = 0.2, I² = 54.3. No publication bias was evident.

Conclusion: Following RYGB, postprandial peak plasma GLP-1, insulin and C-peptide concentrations are greater in individuals with post-bariatric surgery hypoglycaemia, while HbA_1c is less. These observations support the concept that antagonism of GLP-1 would prove beneficial in the management of individuals with hypoglycaemia following RYGB.PROSPERO Registration Number: CRD42021287515.

Polycystic ovary syndrome (PCOS) is recognized as one of the most prevalent endocrinopathy in women at reproductive age. As affected women tend to have poorer assisted reproductive technology (ART) outcomes, PCOS has been suggested to endanger oocyte quality and competence development. The aim of this systematic review was to summarize the available evidence on how the follicular fluid (FF) profile of women with PCOS undergoing in vitro fertilization (IVF) treatment differs from the FF of normo-ovulatory women. For that, an electronic search in PubMed and Web of Science databases was conducted (up to December 2021). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA guidelines were followed, and the Newcastle-Ottawa Scale was used to assess the risk of bias in the included studies. Data retrieved from papers included (n=42), revealed that the FF composition of women with PCOS compared to those without PCOS predominantly diverged at the following molecular classes: oxidative stress, inflammatory biomarkers, growth factors and hormones. Among those biomarkers, some were proposed as being closely related to pathophysiological processes, strengthening the hypothesis that low-grade inflammation and oxidative stress play a critical role in the pathogenesis of PCOS. Notwithstanding, it should be noticed that the available data on PCOS FF fingerprints derives from a limited number of studies conducted in a relatively small number of subjects. Furthermore, phenotypic heterogeneity of PCOS hampers wider comparisons and weakens putative conclusions. Therefore, future studies should be focused at comparing well characterized patient subgroups according to phenotypes.

Non-alcoholic fatty liver disease (NAFLD) is by far the most prevalent form of liver disease worldwide. It's also the leading cause of liver-related hospitalizations and deaths. Furthermore, there is a link between obesity and NAFLD risk. A projected 25% of the world's population grieves from NAFLD, making it the most common chronic liver disorder. Several factors, such as obesity, oxidative stress, and insulin resistance, typically accompany NAFLD. Weight loss, lipid-lowering agents, thiazolidinediones, and metformin help prominently control NAFLD. Interestingly, pre-clinical studies demonstrate gut microbiota's potential causal role in NAFLD. Increased intestinal permeability and unhindered transport of microbial metabolites into the liver are the major disruptions due to gut microbiome dysbiosis, contributing to the development of NAFLD by dysregulating the gut-liver axis. Hence, altering the pathogenic bacterial population using probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) could benefit patients with NAFLD. Therefore, it is crucial to acknowledge the importance of microbiota-mediated therapeutic approaches for NAFLD and comprehend the underlying mechanisms that establish a connection between NAFLD and gut microbiota. This review provides a comprehensive overview of the affiliation between dysbiosis of gut microbiota and the progress of NAFLD, as well as the potential benefits of prebiotic, probiotic, synbiotic supplementation, and FMT in obese individuals with NAFLD.

White adipose tissue (WAT) is an important endocrine organ that regulates systemic energy metabolism. In metabolically unhealthy obesity, adipocytes become dysfunctional through hypertrophic mechanisms associated with a reduced endocrine function, reduced mitochondrial function, but increased inflammation, fibrosis, and extracellular remodelling. A pathologic WAT remodelling promotes systemic lipotoxicity characterized by fat accumulation in tissues such as muscle and liver, leading to systemic insulin resistance and type 2 diabetes. Several lines of evidence from human and animal studies suggest a link between unhealthy obesity and adipocyte mitochondrial dysfunction, and interventions that improve mitochondrial function may reduce the risk of obesity-associated diseases. This review discusses the importance of mitochondrial function and metabolism in human adipocyte biology and intercellular communication mechanisms within WAT. Moreover, a selected interventional approach for better adipocyte mitochondrial metabolism in humans is reviewed. A greater understanding of mitochondrial bioenergetics in WAT might provide novel therapeutic opportunities to prevent or restore dysfunctional adipose tissue in obesity-associated diseases.

The incidence of childhood obesity and metabolic syndrome has grown notably in the last years, becoming major public health burdens in developed countries. Nowadays, oxidative stress is well-recognized to be closely associated with the onset and progression of several obesity-related complications within the framework of a complex crosstalk involving other intertwined pathogenic events, such as inflammation, insulin disturbances, and dyslipidemia. Thus, understanding the molecular basis behind these oxidative dysregulations could provide new approaches for the diagnosis, prevention, and treatment of childhood obesity and associated disorders. In this respect, the transcriptomic characterization of miRNAs bares great potential because of their involvement in post-transcriptional modulation of genetic expression. Herein, we provide a comprehensive literature revision gathering state-of-the-art research into the association between childhood obesity, metabolic syndrome, and miRNAs. We put special emphasis on the potential role of miRNAs in modulating obesity-related pathogenic events, with particular focus on oxidative stress.