Reviews in Endocrine & Metabolic Disorders最新文献

The recent incorporation of immune checkpoint inhibitors targeting the PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways into the therapeutic armamentarium of cancer has increased the need to understand the correlation between the immune system, autoimmunity, and malignant neoplasms. Both autoimmune thyroid diseases and thyroid cancer are common clinical conditions. The molecular pathology of autoimmune thyroid diseases is characterized by the important impact of the PD-1/PD-L1 axis, an important inhibitory pathway involved in the regulation of T-cell responses. Insufficient inhibitory pathways may prone the thyroid tissue to a self-destructive immune response that leads to hypothyroidism. On the other hand, the PD-1/PD-L1 axis and other co-inhibitory pathways are the cornerstones of the immune escape mechanisms in thyroid cancer, which is a mechanism through which the immune response fails to recognize and eradicate thyroid tumor cells. This common mechanism raises the idea that thyroid autoimmunity and thyroid cancer may be opposite sides of the same coin, meaning that both conditions share similar molecular signatures. When associated with thyroid autoimmunity, thyroid cancer may have a less aggressive presentation, even though the molecular explanation of this clinical consequence is unclear. More studies are warranted to elucidate the molecular link between thyroid autoimmune disease and thyroid cancer. The prognostic impact that thyroid autoimmune disease, especially chronic lymphocytic thyroiditis, may exert on thyroid cancer raises important insights that can help physicians to better individualize the management of patients with thyroid cancer.

Ultrasound (US) of the thyroid has been used as a diagnostic tool since the late 1960s. US is the most important imaging tool for diagnosing thyroid disease. In the majority of cases a correct diagnosis can already be made in synopsis of the sonographic together with clinical findings and basal thyroid hormone parameters. However, the characterization of thyroid nodules by US remains challenging. The introduction of Thyroid Imaging Reporting and Data Systems (TIRADSs) has improved diagnostic accuracy of thyroid cancer significantly. Newer techniques such as elastography, superb microvascular imaging (SMI), contrast enhanced ultrasound (CEUS) and multiparametric ultrasound (MPUS) expand diagnostic options and tools further. In addition, the use of artificial intelligence (AI) is a promising tool to improve and simplify diagnostics of thyroid nodules and there is evidence that AI can exceed the performance of humans. Combining different US techniques with the introduction of new software, the use of AI, FNB as well as molecular markers might pave the way for a completely new area of diagnostic accuracy in thyroid disease. Finally, interventional ultrasound using US-guided thermal ablation (TA) procedures are increasingly proposed as therapy options for benign as well as malignant thyroid diseases.

In recent years, a growing number of studies have examined the relationship between thyroid pathophysiology and intestinal microbiota composition. The reciprocal influence between these two entities has been proven so extensive that some authors coined the term "gut-thyroid axis". However, since some papers reported conflicting results, several aspects of this correlation need to be clarified. This systematic review was conceived to achieve more robust information about: 1)the characteristics of gut microbiota composition in patients with the more common morphological, functional and autoimmune disorders of the thyroid; 2)the influence of gut microbial composition on micronutrients that are essential for the maintenance of thyroid homeostasis; 3)the effect of probiotics, prebiotics and synbiotics, some of the most popular over-the-counter products, on thyroid balance; 4)the opportunity to use specific dietary advice. The literature evaluation was made by three authors independently. A five steps strategy was a priori adopted. After duplicates removal, 1106 records were initially found and 38 reviews were finally included in the analysis. The systematic reviews of reviews found that: 1) some significant variations characterize the gut microbiota composition in patients with thyroid disorders. However, geographical clustering of most of the studies prevents drawing definitive conclusions on this topic; 2) the available knowledge about the effect of probiotics and synbiotics are not strong enough to suggest the routine use of these compounds in patients with thyroid disorders; 3) specific elimination nutrition should not be routine suggested to patients, which, instead have to be checked for possible micronutrients and vitamins deficiency, often owed to gastrointestinal autoimmune comorbidities.

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.