Endocrine Abstracts

Objective: Glucocorticoid excess impairs immune function, thereby predisposing patients with endogenous Cushing’s syndrome (CS) to infections. However, it is still not clear whether there is a CS-subtype specific pattern in white blood cell (WBC) and WBC differential (WBCD) count.Methods: Retrospective monocentric cohort study in patients with either overt endogenous CS or adrenal adenomas with autonomous cortisol secretion (ACS), with WBC and WBCD ...

Background: Molecular mechanisms of malignant adrenocortical tumorigenesis remain elusive despite previous comprehensive genomic studies. Nonetheless, cellular heterogeneity of primary, recurrent and metastatic adrenocortical carcinoma (ACC) haven’t been fully investigated.Aim: To characterize the molecular profile of different cell subtypes in primary, recurrent and metastatic ACC by single-nuclei RNA sequencing (snRNA-Seq), using adult human norma...

Context: Endogenous Cushing syndrome (CS) is associated with hematological abnormalities. Nevertheless, conflicting data have been reported on erythropoiesis. Some studies reported an association between CS and anemia in men, whereas others described erythrocytosis in affected patients. Furthermore, it is unclear whether there are CS subtype-specific changes in red blood cells (RBC) parameters.Objective: To investigate sex and subtype-specific changes in...

Background: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC). We have found that mitotane leads to endoplasmic reticulum stress and decreased viability in ACC cells. It is not known by which downstream mechanisms cell death is induced by mitotane.Aim: To characterize the mechanisms underlying cell death resulting from mitotane treatment in ACC cells.Methods: Lipid peroxidation in the ACC cell line ...

Context: Adrenocortical carcinoma (ACC) are endocrine malignant neoplasms associated with severe aggressiveness. By applying of ‘multiple omics’ approach, we recently categorized ACC patients based on their steroidogenic activity and expression of immune activation marker, which is along with prognosis; an ‘immune’ phenotype with good and a ‘steroid’ phenotype with bad outcome.Hypothesis: Our central hypothesis focuses on th...

Ad Adrenocortical carcinoma (ACC) is an aggressive tumour and treatment remains unsatisfactory in advanced disease. Activation of epithelial to mesenchymal transition (EMT) is considered causative for metastatic spread in a variety of human cancers. Accordingly, new drugs were developed specifically targeting EMT with a focus on hepatocyte growth factor (HGF)/HGF receptor (c-MET) and fibroblast growth factor (FGF)/FGF receptor (FGFR) signalling.We here a...

In a previous study we found mutations in the main catalytic subunit of protein kinase A (PKA Cα) to be responsible for cortisol-secreting adrenocortical adenomas (ACAs). These mutations interfere with the formation of a stable holoenzyme, thus causing constitutive PKA activation. More recently, we identified additional mutations affecting PKA Cα in ACAs associated with overt Cushing syndrome: Ser213Arg_Leu212_Lys214insIle-Ile-Leu-Arg, Cys200_Gly201insVal, Trp197Arg,...

Background: Adrenocortical tumours consist of frequent adrenocortical adenomas (ACA) and highly malignant (ACC) with a still incompletely understood pathogenesis. Dysregulation of Notch signalling pathway is implicated in several cancers with oncogenic or tumour suppressor functions. Copy number gains and over-expression of Jagged1, a ligand of Notch receptor, was reported in ACC. The aim of the study was to evaluate the expression of Jagged1 and other Notch-r...

Recently, mutations in the PRKACA (catalytic subunit α of the PKA) gene have been identified as causative in 35% of adrenocortical adenomas (ACA) with overt Cushing’s syndrome (Beuschlein et al. 2014). These mutations lead to constitutive activation of PKA signaling and subsequently to an excessive production of cortisol. Protein kinase A is a heterotetramer consisting of two catalytic and two regulatory subunits with several isoforms (Cα, β, &#947...

Background: Mitotane is the only approved treatment for advanced adrenocortical carcinoma and was shown to inhibit Sterol-O-Acyl transferase 1 (SOAT1) which leads to the depletion of cholesterol esters and increase of free cholesterol in the ACC cell line H295R. Downstream activation of the endoplasmic reticulum stress (ER-stress) pathway results in decreased adrenocortical cell viability.Aim: To better characterize the effects of SOAT1 inhibition in ACC...