Endocrine Abstracts

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: Heterozygous activating somatic mutations in the catalytic subunit α (Cα) of Protein Kinase A (PKA) underlie 30–40% of cortisol producing adrenocortical adenomas (CPA). The activity of the catalytic subunits α,β,γ is controlled by the regulatory subunits (Iα,Iβ, IIα, IIβ). Previous reports found uncommonly reduced levels of RIIβ in CPA compared to other adrenocortical tumors.Aim: Investig...

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...

Aim: To determine diagnostic performance of normetanephrine (NMN) and metanephrine (MN) measured by an enzyme immunoassay (EIA) compared with liquid chromatographic–tandem mass spectrometry (LC-MS/MS).Methods: Subjects included 341 patients (174 males) with a mean age of 52 year (range 13–86) tested for PHEO, which was confirmed in 54 patients. Samples where collected from fasting patients after 30 min of supine rest and analyzed for NMN, MN an...

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.</...

Introduction: O,p’DDD is the drug of choice for patients with adrenocortical carcinoma (ACC). Monitoring o,p’DDD serum level has been proposed as predictor of tumour response. Measurement of o,p’DDD metabolites involved in the active pathway may provide an improved prediction of o,p’DDD activity. The objective of our study was to (1)to confirm the currently used threshold o,p’DDD serum level of 14mg/l for achieving a tumour response and (2)compare the ...

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)...