Our data demonstrated high penetrance of NF-PETs in 15- to 20-year-old MEN1 patients. The high percentage of the patients presenting consensus criteria for surgery for NF-PET alone or NF-PET/insulinoma suggests a potential benefit for the periodic surveillance of these tumors in this age group.

Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1-related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.

Objective: To date, no evidence of robust genotype-phenotype correlation or disease modifiers for multiple endocrine neoplasia type 1 (MEN1) syndrome has been described, leaving the highly variable clinical presentation of patients unaccounted for. Design: As the CDKN1B (p27) gene causes MEN4 syndrome and it is transcriptionally regulated by the product of the MEN1 gene (menin), we sought to analyze whether p27 influences the phenotype of MEN1-mutated patients. The cohort consisted of 100 patients carrying germline MEN1 gene mutations and 855 population-matched control individuals. Methods: Genotyping of the coding p27 c.326TOG (V109G) variant was performed by sequencing and restriction site digestion, and the genotypes were associated with clinical parameters by calculating odds ratios (ORs) and their 95% CIs using logistic regression. Results: There were significant differences in p27 V109G allele frequencies between controls and MEN1-mutated patients (ORZ2.55, PZ0.019, CIZ1.013-5.76). Among patients who are R30 years old carrying truncating MEN1 mutations, the T allele was strongly associated with susceptibility to tumors in multiple glands (three to four glands affected vs one to two glands affected; ORZ18.33; PZ0.002, CIZ2. 88-16.41). This finding remained significant after the Bonferroni's multiple testing correction, indicating a robust association. No correlations were observed with the development of MEN1-related tumors such as hyperparathyroidism, pituitary adenomas, and enteropancreatic and adrenocortical tumors. European Journal of EndocrinologyClinical Study V C Longuini and others p27 rs2066827, an MEN1 syndrome modifier

Germline mutations in p27 kip1 are associated with increased susceptibility to multiple endocrine neoplasias (MEN) both in rats and humans; however, the potential role of common polymorphisms of this gene in endocrine tumor susceptibility and tumorigenesis remains mostly unrecognized. To assess the risk associated with polymorphism rs2066827 (p27-V109G), we genotyped a large cohort of Brazilian patients with sporadic endocrine tumors (pituitary adenomas, nZ252; pheochromocytomas, nZ125; medullary thyroid carcinoma, nZ51; and parathyroid adenomas, nZ19) and 885 population-matched healthy controls and determined the odds ratios and 95% CIs. Significant associations were found for the group of patients with pituitary adenomas (PZ0.01), particularly for those with ACTH-secreting pituitary adenomas (PZ0.005). In contrast, no association was found with GH-secreting pituitary tumors alone or with the sporadic counterpart of MEN2-component neoplasias. Our in vitro analyses revealed increased colony formation and cell growth rate for an AtT20 corticotropin mouse cell line overexpressing the p27-V109G variant compared with cells transfected with the WT p27. However, the genotypic effects in genetic and in vitro approaches were divergent. In accordance with our genetic data showing specificity for ACTH-secreting pituitary tissues, the overexpression of p27-V109G in a GH3 somatotropin rat cell line resulted in no difference compared with the WT. Pituitary tumors are one of the major clinical components of syndromes associated with the p27 pathogenic mutations MENX and MEN4. Our genetic and in vitro data indicate that the common polymorphism rs2066827 may play a role in corticotropinoma susceptibility and tumorigenesis through a molecular mechanism not fully understood thus far.

Digital ulcers are one of the earliest and most disabling manifestations of systemic sclerosis (SSc). We report the clinical case of a female patient with SSc and severe digital ulcers, recurrent and refractory to the classic treatments to whom it was prescribed off-label macitentan with complete resolution of the condition.

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Aims In Portugal, in the last 5 years, no study has published recent data regarding outcomes of patients with acute decompensated heart failure (ADHF). We aimed to determine the characteristics and outcomes of a large contemporaneous Portuguese cohort of ADHF patients admitted to our emergency department (ED). Methods and resultsWe conducted a retrospective, study of all 1024 patients admitted to our ED with a discharge diagnosis of ADHF from November 2016 to December 2017. Baseline clinical data and outcomes {in-hospital, 30 day, and follow-up allcause mortality, and readmissions; median follow-up, 5 months; interquartile range [(IQR), 3-11 months]} were determined. Mean age was 78 ± 10 years, and 53% were male; of the 1024 patients, 554 (54%) were hospitalized. The median hospitalization length was 9 (IQR, 5-15) days, and in-hospital mortality was 12.7%. Hospitalized patients were predominantly men (56% vs. 47%; P < 0.001), younger (77 ± 9 vs. 79 ± 11 years; P = 0.002) and had higher creatinine values and B-type natriuretic peptide values (P < 0.001) than discharged patients. Patients with prior hospitalization had lower 30 day readmission rate (8% vs. 14%; P = 0.01), same overall readmission rate (30% vs. 32%), and higher 30 day (13% vs. 5%; P < 0.001) and overall mortality rates (28% vs. 15%; P < 0.001). Conclusions Approximately half of the patients admitted to the ED were hospitalized. Of these, only 8% were readmitted in the ED within 30 days. The clinical and analytical status in the ED are important predictors of hospitalization.Additional supporting information may be found online in the Supporting Information section at the end of the article. Data S1. Supporting information.Analysis of acute decompensated heart failure outcomes 557 ESC Heart Failure 2020; 7: 551-558

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