Minerva endocrinology最新文献

Aggressive pituitary tumors are a subset of pituitary neoplasms, characterized by unusually fast growth rate, invasiveness and overall resistance to optimized standard treatment. When metastases are present, the term pituitary carcinoma is employed. After failure of standard treatments, current guidelines recommend first-line temozolomide monotherapy. However, a significant number of patients do not respond to temozolomide, or experience disease progression following its discontinuation; in these latter cases, re-challenge with temozolomide is generally advised, although the reported outcomes have been less satisfactory. Although no alternative therapies have been formally recommended after temozolomide failure, growing evidence regarding potential second- or third-line therapeutic strategies has emerged. In the present work, we reviewed the available evidence published up to April 2023 involving the most relevant therapies employed so far, namely immune checkpoint inhibitors, bevacizumab, peptide radionuclide receptor therapy, tyrosine kinase inhibitors and mTOR inhibitors. For each treatment, we report efficacy and safety outcomes, along with data regarding potential predictors of response. Overall, immune checkpoint inhibitors and bevacizumab are showing the most promise as therapeutic options after temozolomide failure. The former showed better responses in pituitary carcinomas. Peptide radionuclide receptor therapy has also showed some efficacy in these tumors, while tyrosine kinase inhibitors and mTOR inhibitors have exhibited so far limited or no efficacy. Further studies, as well as an individualized, patient-tailored approach, are clearly needed. In addition, we report an unpublished case of a silent corticotroph pituitary carcinoma that progressed under dual immunotherapy, and then showed stable disease under a combination of lomustine and bevacizumab.

Introduction: The association between betatrophin level and type 2 diabetes mellitus (T2DM) is a subject of controversy, and the reasons for conflicting results have been poorly explained. To address this gap, we conducted a meta-analysis of relevant studies to obtain a more comprehensive estimate and draw a more accurate conclusion.

Evidence acquisition: This study included literature published up to June 2023. We searched for relevant studies in the Web of Science and PubMed databases. We utilized STATA 12.0 software to calculate the standard mean difference (SMD) and 95% confidence interval (CI) to compare circulating betatrophin levels between individuals with T2DM and healthy controls (HCs).

Evidence synthesis: The meta-analysis revealed a significantly higher circulating betatrophin level in individuals with T2DM compared to HC, using a random effects model [mean value of betatrophin level (T2DM vs. HC): 388,685.23 vs. 304,857.04 pg/mL; SMD=1.37; 95%CI: 1.01, 1.73]. Subgroup analysis indicated a higher circulating betatrophin level in T2DM compared to HC among Asian individuals, while no significant difference in circulating betatrophin level was observed between T2DM and HC among Caucasian individuals (Asian: SMD=1.65; 95%CI: 1.23, 2.06; Caucasian: SMD=0.50; 95%CI: -0.21, 1.20). Additionally, subgroup analysis revealed increased plasma and serum betatrophin levels in T2DM compared to HC (plasma: SMD=1.30; 95%CI: 0.72, 1.88; serum: SMD=1.47; 95%CI: 0.98, 1.96).

Conclusions: This meta-analysis provides evidence of elevated levels of betatrophin in individuals with T2DM, suggesting that betatrophin may serve as a potential diagnostic biomarker for T2DM.

Glucagon-like peptide-1 (GLP-1) receptor agonists are used in diabetes management and can have a potential application in cancer therapy. While their involvement in cancer treatment is still being studied, recent research suggests they may have benefits in cancer therapy. A comprehensive literature search was conducted using search engines like Google Scholar, Scopus, and PubMed to explore the effects of GLP-1 receptor agonists in tumor suppression and regression. Mostly in-vitro studies on GLP-1 receptor agonists have shown promising effects in inhibiting cancer cell growth, inducing apoptosis, and modulating angiogenesis and have been reported to be beneficial in colon, prostate, gall bladder, ovarian, and endometrial carcinomas. However, concerns have been raised about potential tumorigeneses, as liraglutide has been reported to be associated with increased incidence of breast, thyroid, and pancreatic carcinomas. Whereas combination therapy of exendin-4 with gemcitabine may be beneficial in pancreatic cancer. GLP-1 receptor agonists may have significant potential in oncology, due to their various mechanisms of action and favorable safety profiles. Limited clinical application, lack of awareness, and the need for further research are current barriers. Future studies should focus on optimal dosage, patient selection, and interdisciplinary collaboration to integrate GLP-1 receptor agonists into routine oncological practice for improved outcomes, warranting large randomized clinical trials in this field.

Background: Due to the low incidence and heterogeneous behavior of medullary thyroid carcinoma (MTC), its prognostic factors are still not well stablished. While several large studies have investigated the impact of gender in differentiated thyroid cancer (DTC), its role in MTC outcomes remains controversial. We aim to identify MTC prognostic features, specially focusing on the role of gender.

Methods: The present study is a retrospective analysis of 76 patients diagnosed with MTC between 1984 and 2018 at a Portuguese Comprehensive Cancer Center.

Results: Patients presented a median age at diagnosis of 49 years and multiple endocrine neoplasia type 2 (MEN2) was identified in 27.6% of them, with those individuals being significantly younger (P<0.001). Most cases were diagnosed as stage IV disease (46.9%), except for the subgroup detected through presymptomatic genetic screening (55.6% at stage I). The 5- and 10-year survival rates were 87.6% and 75.6%, respectively. Univariate analysis identified male gender (P=0.010), age ≥45 years (P=0.007), presence of distant metastasis at diagnosis (P<0.01), capsule invasion (P=0.004), extrathyroidal invasion (P=0.003) and absence of biochemical cure after surgery (P=0.042) as having a negative impact on prognosis. On multivariate analysis, male gender (P=0.046) remained an independent predictor of mortality, as well as an older age (P<0.001) and the presence of distant metastases (P=0.012).

Conclusions: Male gender independently predicted worse survival in MTC patients even after adjusting for age and disease stage. The few older studies on the topic pointed to a behavioral explanation regarding medical care seeking patterns by men, but our study and newer genetic and basic-science oriented publications raise the possibility of a true biological difference between genders in the tumorigenesis of MTC that should me further investigated.

Type 1 diabetes (T1D) is an organ-specific chronic autoimmune disease mediated by autoreactive T cells. ZnT8 is a pancreatic islet-specific zinc transporter that is mainly located in β cells. It not only participates in the synthesis, storage and secretion of insulin but also maintains the structural integrity of insulin. ZnT8 is the main autoantigen recognized by autoreactive CD8⁺ T cells in children and adults with T1D. This article summarizes the latest research results on the T lymphocyte epitope and B lymphocyte epitope of ZnT8 in the current literature. The structure and expression of ZnT8, the role of ZnT8 in insulin synthesis and its role in autoimmunity are reviewed. ZnT8 is the primary autoantigen of T1D and is specifically expressed in pancreatic islets. Thus, it is one of biomarkers for the diagnosis of T1D. It has broad prospects for further research on immunomodulators for the treatment of T1D.

Background: Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of autoimmune chronic inflammatory conditions and papillary thyroid carcinoma (PTC). We hypothesized that, as VEGF expression is increased both in PTC and in lymphocytic thyroiditis (LT), it may stimulate the development of PTC in patients with LT. To evaluate this, we examined both tumor and adjacent non-tumoral tissues of PTC patients with and without LT.

Methods: A total of 50 patients with PTC (52.50±7.41 years) and 17 patients with nodular goiter (NG) (50.47±10.38 years) were included in the study. According to the presence of LT, patients with PTC were further divided into two groups. Immunohistochemical analyses of VEGF were conducted in all patients and for PTC patients, both tumor tissue and adjacent non-tumoral tissue were evaluated.

Results: The scores for intensity of staining and percentage of labeled thyrocytes for VEGF were found to be significantly higher in the PTC patients than in the NG patients (P<0.001, P<0.001, respectively). The tumor tissue revealed similar scores for PTC patients with LT and without LT. However, the scores in adjacent non-tumoral tissue were higher in PTC patients with LT than in patients without LT (P=0.004, P=0.01, respectively).

Conclusions: To the best of our knowledge, our results are the first to demonstrate that the expression of VEGF in adjacent non-tumoral tissue were higher in PTC patients with LT than in those without, which shows a possible role of VEGF expression in the progression of PTC in the presence of LT.

Background: The aim of this study was to analyze the prevalence of primary and secondary hyperparathyroidism in patients with primary aldosteronism (PA), and its implication on cardiovascular and metabolic outcomes.

Methods: A retrospective study of patients with PA (exposed cohort, N.=44) and all hypertensive (EH) patients with adrenal lesions without PA nor other adrenal hypersecretion (non-exposed cohort, N.=41) on follow-up at our center between 2016 and 2020.

Results: The mean age of patients with PA and EH was 55.1±14.13 and 66.3±10.93 (P<0.001), and 50% of PA and 39.0% of EH were women (P=0.309). At diagnosis, the prevalence of primary hyperparathyroidism in PA was of 18.2%, and all were normocalcemic hyperparathyroidism cases. Globally, no differences were found in the prevalence of primary hyperparathyroidism compared to EH (18.2% vs. 29.3%, P=0.229), but hypercalcemic primary hyperparathyroidism was significantly more prevalent in EH patients than in PA (22.0% vs. 0%, P=0.001). There were 47.7% (N.=21) cases of secondary hyperparathyroidism in patients with PA (4 due to chronic kidney disease (CKD) and vitamin D deficiency, and 17 due to vitamin D deficiency alone). The cardiometabolic profile of patients with PA and hyperparathyroidism (N.=29) was similar to of those patients without hyperparathyroidism (N.=15) at diagnosis and after a median follow-up of 3.6 years (interquartile range 1.1-5.9).

Conclusions: Although primary and secondary hyperparathyroidism are common in patients with PA, their prevalence was similar than the observed in EH patients. Primary hyperparathyroidism is usually mild in PA, appearing as normocalcemic forms. No negative implications of the hyperparathyroidism in the cardiometabolic profile of PA were observed.

Background: Besides growth acceleration, growth hormone (GH) therapy of GH deficient (GHD) children improves body composition by decreasing body fat. This effect is due to GH interaction with lipid and carbohydrate metabolism, possibly also mediated by adipokines secreted by adipose tissue, and ghrelin. This study aimed to assess the impact of one-year GH replacement therapy on the metabolic profile, adipokines, and acylated/unacylated ghrelin of prepubertal children with GHD.

Methods: Prospective observational study of 42 non-obese, prepubertal children with GHD followed up for twelve months. Mean lipid, carbohydrate, adipokine profiles, acylated/unacylated ghrelin, and body composition data before therapy onset were compared with measurements obtained after 6 and 12 months of GH therapy.

Results: Total body fat content and body fat percentage decreased significantly, while the lipid profile improved over the study period in the 42 GHD children with a mean age of 9.2±2.6 years. The levels of leptin and unacylated ghrelin decreased significantly, whereas adiponectin and acylated ghrelin values increased after GH therapy. In regression analysis models, GH treatment (reflected by increased absolute values or standard deviations of IGF1) influences the variation of leptin and adiponectin, but not ghrelin, independently of body composition - lean or fat mass.

Conclusions: GH replacement therapy improves body composition, lipid, and adipokine profile in GHD children. Also, GH replacement therapy directly impacts leptin and adiponectin concentrations, independently of body composition. Further research is needed to identify the molecular mechanisms and metabolic pathways by which the GH/IGF1 axis influences adipokines secretion.