Endocrine Abstracts

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...

Introduction: Adrenocortical tumours comprise frequent adenomas (ACA) and rare highly malignant carcinoma (ACC). Livin/ML-IAP/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumorigenesis, mostly through the inhibition of caspase-3. Aim of the study was to evaluate the expression of livin/BIRC7 in normal and neoplastic adrenal glands.Methods: The mRNA expression of BIRC7, its isoforms livin α...

Background: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC). Molecular events leading to cell death in adrenocortical cells are unknown preventing the development of drugs with improved efficacy-toxicity ratio.Methods: We employed the ACC model cell line NCI-H295 to investigate the effects of mitotane on genome-wide mRNA expression using microarray analysis. Several algorithms were used to delineate signaling pathways t...

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: Glucocorticoids (GC) are used for immunosuppression in many clinical conditions. Pre-clinical and early clinical studies suggested that the induction of regulatory T (Treg) cells contributes to the immunosupressive effects of GCs. However, in the hitherto reported clinical studies only patients with ongoing autoimmune diseases were included. Our goal, therefore, was to determine the influence of exogenous GCs in vivo in immunocompetent subjects and mice.</...

Objectives: Endocrine gland-derived vascular endothelial growth factor (EG-VEGF; also termed prokineticin-1) has been identified as a mitogen preferable for the endothelium of steroidogenic glands (1). EG-VEGF and its receptors (prokineticin receptors 1 and 2; PKR1 and 2) are highly expressed in the normal adrenal gland and an autocrine mitogenic loop has been proposed (2). Therefore, we investigated the expression of EG-VEGF and its receptors in adrenocortical carcinoma (ACC)...

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...

ContextThe occurrence of different subtypes of endogenous Cushing’s syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing’s disease (CD).Case DescriptionA 50-year-old female was diagnosed with ACTH-independent CS and a left-sided adrenal adenoma in January 2015. After ...

Background: Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing’s syndrome. The clinical application of adrenal venous sampling (AVS) in diagnostic work-up for PBMAH is still controversially discussed. AVS might be useful in evaluating the predominant side and guiding the decision for unilateral adrenalectomy in PBMAH.Objectives: Our aim was to evaluate whether certain metabolites in AVS samp...

Context: The occurrence of different subtypes of endogenous Cushing’s syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing&apos;s disease (CD).Case Description: A 50-year-old female was diagnosed with ACTH-independent CS and a left-sided adrenal adenoma in January 2015. After adrenalectomy and histopathological co...