Endocrine Abstracts

Background: Endogenous Cushing’s syndrome (CS) is associated with increased susceptibility to infections and mortality. Previously reported effects of hypercortisolism on immune function include a reduced CD4+/CD8+ ratio with a shift towards IL4+T helper cells (Th2), suppressed NK-cell cytotoxic activity as well as a low-grade inflammatory profile.Aim: This cross-sectional single center study aims to compare immune phenotype in patients with overt C...

Adrenocortical carcinomas (ACC) are associated with heterogeneous prognosis and limited treatment options for advanced stages. Until now no efficient targeted therapies have been identified. This study aims to identify possible new molecular drug targets for a future personalized therapeutic approach. RNA was isolated from 40 formalin-fixed paraffin-embedded tumor samples from ACC patients (26F&14M, median age 46 yrs) with known genetic background (Lippert et al. JCEM ...

Adrenocortical carcinoma (ACC) is an orphan tumor entity the pathogenesis of which is poorly understood. In advanced tumour stages, prognosis is unfavorable, but biomarkers for early diagnosis are lacking. MALDI-Mass Spectrometry Imaging (MALDI-MSI) enables semi-quantitative detection of a broad spectrum of analytes including endogenous cell metabolites in tissue sections. MALDI-MSI was used as a discovery approach to analyse tissue specimens of 72 ACC patients in FFPE tissue ...

Adrenocortical carcinoma (ACC) is a rare tumor with heterogeneous outcome and no available targeted therapy. The aim of the study is to identify prognostic molecular markers and novel potential drug targets.A total of 43 FFPE tumor samples were retrospectively investigated for somatic mutations and copy number variations (CNV) by next-generation sequencing (160 cancer-related genes, Qiagen). Gene expression was evaluated by quantitative RT-PCR in a subgr...

Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma (ACC) and we recently demonstrated that a high expression of cytochrome P450 2W1 (CYP2W1) correlated with response to mitotane. The association between CYP2W1 alleles and a generally increased cancer risk is under debate. Aim of the study was to evaluate the frequency of CYP2W1 polymorphisms and its correlation with the response to mitotane treatment in ACC patients.<p class="abstext"...

Context: Anaplastic (ATC) thyroid carcinoma is an orphan disease accounting for about 2% of all malignant thyroid tumors. ATC confers a dismal prognosis and standard treatment is not established.Objective: To describe the epidemiology, current treatment regimens and outcome of ATC, to identify clinical prognostic markers and treatment factors associated with improved prognosis. To establish a consensus treatment schedule.Design: Re...

Background: Cushing’s syndrome (CS) is a chronic disorder characterized by endogenous cortisol excess resulting in long-term metabolic and cardiovascular consequences. The identification of metabolic alterations related to hypercortisolism could be beneficial in tailoring treatments of co-morbidities. Our aim was to characterize the metabolic alterations of patients with hypercortisolism by targeted plasma metabolomic profiling.Methods: Subjects (<e...

Background: Adrenocortical carcinoma (ACC) has a heterogeneous prognosis and current medical therapies have limited efficacy in its advanced stages. Genome-wide multi-omics-studies identified molecular patterns associated with clinical outcome. Here, we aimed at identifying a molecular signature useful for both personalized prognostic stratification and druggable targets, using methods applicable in clinical routine.Methods: 117 tumor samples from 107 AC...

Background: The multi-tyrosine kinase inhibitor sunitinib is approved for advanced renal cell carcinoma and gastrointestinal stroma tumors. It targets both tumor vessels and malignant cells. Animal experiments have pointed to a direct adrenotoxic effect of the drug.Aims: We hypothesized that sunitinib may inhibit proliferation of adrenocortical cancer (ACC) cells and influence adrenal steroid hormone synthesis.Results: Sunitinib re...

Introduction: Adrenocortical carcinoma (ACC) is a rare, aggressive tumour with unsatisfactory treatment options in advanced disease. Activation of epithelial to mesenchymal transition (EMT) has been described as causative of metastatic spread in a variety of human cancers. Accordingly, new drugs were developed specifically targeting EMT with a focus on HGF/c-MET and FGF/FGFR signalling. We here asked whether EMT is a relevant mechanism in ACC.Methods: Ex...