Reviews in Endocrine & Metabolic Disorders最新文献

Thyroid cancer has shown a parallel increase with diabetes in the last few years. This narrative review aims to explain the association between these two entities, focusing on insulin resistance as the mediator and exploring the effects of antidiabetic agents on thyroid cancer incidence and progression.We searched Pubmed for English-written articles on insulin resistance, diabetes, antidiabetic treatments, and thyroid cancer reported from January 2019 to April 2023. Exclusion criteria were preclinical and clinical studies involving a population with thyroid dysfunction, benign nodular goiter, or those that only analyzed thyroid cancer's association with obesity.The results of the narrative literature review revealed 96 articles. Additionally, four studies from a manual search were retrieved. After the exclusion criteria were applied, we included 20 studies. Out of 8 studies on insulin-resistant or Metabolic Syndrome patients, all suggest a positive association with thyroid cancer. At the same time, for diabetes, four out of five publications support a link with thyroid cancer. The seven remaining studies on antidiabetics suggest that metformin might benefit thyroid cancer. In contrast, the evidence for an association between Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and increased thyroid cancer findings is limited.In conclusion, the association between thyroid cancer and diabetes may be explained by insulin resistance, as shown in observational studies. However, the causal role is yet to be defined. Although the wide use of different antidiabetic agents has been related to thyroid cancer prevalence and progression, future research with drugs such as metformin or GLP-1 RA is still needed.

Active Surveillance is a non-invasive strategy designed to identify a minority of patients with low-risk papillary thyroid carcinoma who might experience clinical progression and benefit from additional definitive treatments. Global experience suggests that these tumors typically show minimal changes in size during active surveillance, often demonstrating very slow growth or even size reduction. Moreover, the rate of lymph node metastases is low and can be effectively managed through rescue surgery, without impacting cancer-related mortality. However, despite 30 years of experience demonstrating the safety and feasibility of active surveillance for appropriately selected patients, this approach seems to have limited adoption in specific contexts. This limitation can be attributed to various barriers, including disparities in access to accurate information about the indolent nature of this disease and the prevalence of a maximalist mindset among certain patients and medical settings. This review aims to revisit the experience from the last three decades, provide current insights into the clinical outcomes of active surveillance trials, and propose a systematic approach for its implementation. Furthermore, it intends to emphasize the importance of precise patient selection and provides new perspectives in the field.

Anaplastic thyroid cancer (ATC) is an infrequent thyroid tumor that usually occurs in elderly patients. There is often a history of previous differentiated thyroid cancer suggesting a biological progression. It is clinically characterized by a locally invasive cervical mass of rapid onset. Metastases are found at diagnosis in 50% of patients. Due to its adverse prognosis, a prompt diagnosis is crucial. In patients with unresectable or metastatic disease, multimodal therapy (chemotherapy and external beam radiotherapy) has yielded poor outcomes with 12-month overall survival of less than 20%. Recently, significant progress has been made in understanding the oncogenic pathways of ATC, leading to the identification of BRAF V600E mutations as the driver oncogene in nearly 40% of cases. The combination of the BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) showed outstanding response rates in BRAF-mutated ATC and is now considered the standard of care in this setting. Recently, it was shown that neoadjuvant use of DT followed by surgery achieved 24-month overall survival rates of 80%. Although these approaches have changed the management of ATC, effective therapies are still needed for patients with BRAF wild-type ATC, and high-quality evidence is lacking for most aspects of this neoplasia. Additionally, in real-world settings, timely access to multidisciplinary care, molecular testing, and targeted therapies continues to be a challenge. Health policies are warranted to ensure specialized treatment for ATC.The expanding knowledge of ATC´s molecular biology, in addition to the ongoing clinical trials provides hope for the development of further therapeutic options.

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.

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.

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.