Endocrine Abstracts

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...

Adrenocortical carcinoma (ACC) is a very severe endocrine malignancy with poor prognosis. While cancer immunotherapies have revolutionized the treatment of several cancer entities, the results of initial studies of different immune checkpoint inhibitors in ACC were heterogeneous and clinically substantial responses were observed only in a subset of patients. Expression of immune checkpoint molecules - programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T Lymphocytes...

Adrenocortical carcinoma (ACC) is a rare malignancy and most of the therapeutic strategies are not yet prospectively validated. However, several studies have been published in 2010 and preliminary results from two prospective trials are available now.Open adrenalectomy is treatment of choice for resectable tumors. However, two recent retrospective studies provided evidence that a laparoscopic approach might be also a safe alternative in selected cases (e...

Purpose: Mitotane is the reference systemic therapy for adrenocortical carcinoma (ACC), but its mechanism of action and possible predictors of treatment response remain poorly defined. Our aim was to evaluate the gene expression of ribonucleotide reductase large subunit 1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) in ACC as potential biomarkers for clinical outcome and response to mitotane.Experimental design: Forty-five and 47 tiss...

Background: The ESE-ENSAT guidelines emphasize the role of local therapies and suggest radiotherapy (RT) as an individualized treatment in patients with advanced ACC. However, the evidence for this recommendation is very low.Objectives: The aim of this study was to retrospectively investigate the efficacy and tolerance of RT in advanced ACC.Methods: We screened all patients in five European reference centers for ACC since 2000 for ...

Background: Adrenocortical carcinoma is a rare endocrine malignancy with poor prognosis and few treatment options in advanced disease. Immune checkpoint inhibitors (ICI) have been studied in few clinical trials with a limited number of patients in ACC. No real-life data are available so far. In the present study we aimed at evaluating treatment response and safety of ICI treatment in advanced ACC and identifying clinical, biochemical, histological and molecular markers for pre...

Background: Adrenocortical carcinoma (ACC) is an aggressive cancer originating from steroidogenic cells within the adrenal cortex. Unfortunately, half of patients present with metastatic spread upon initial diagnosis, and there is no curative therapy for advanced disease. Genomic analysis has identified that the most aggressive subgroup of ACC patients have overlapping alterations in the WNT/β-catenin pathway and the p53/RB signaling pathway.Objecti...

The European Journal of Endocrinology Prize is awarded to a candidate who has contributed significantly to the advancement of the knowledge in the field of endocrinology through publication. Further information on the prize can be found at http://www.ese-hormones.org/prizes/eje.aspx. This year’s recipient is Prof. Martin Fassnacht. The prize will be presented as part of the ECE 2014 opening ceremony where ...

It is generally accepted that hepatic responses to α-adrenergic agonists are dependent on the redistribution of intracellular and also extracellular Ca2+. Besides, phenylephrine induces significant K+ flux changes and plasma membrane hyperpolarisation. Earlier it was shown that K+ channel blockers as well as chelating of extracellular Ca2+ with EGTA could inhibit phenylephrine-induced metabolic responses and activation of mitoch...

Introduction: Cushing’s disease (CD) is caused by pituitary tumors hypersecreting adrenocorticotropin (ACTH). Until now somatic mutations in the 14-3-3 binding domain of Ubiquitin Specific Peptidase 8 gene (USP8) were the only recurring, driver mutations and were described in about 40% of the 446 CD samples that have been analysed wordwide. We wanted to assess if other driver mutations might be the pathogenetic cause of CD in those tumors without USP8 mu...