Endocrine Abstracts

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 per million per year. Prognosis of ACC is generally poor but variable and therapeutic approaches are scarce. While surgical resection presents the best option for definitive cure, mitotane remains the only approved drug for adjuvant therapy in ACC to date. Advancements regarding novel treatment strategies as well as fostered understanding of potential drivers of adrenocortical carcinogenesis ...

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) and its ligand PD-L1 - has been shown to pred...

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...

Adrenocortical carcinoma (ACC) is a rare malignant tumour with heterogeneous outcome. Prognostic classification relies on individual clinical/histopathological parameters that have limited performance. Recent studies proposed the use of selected DNA-based biomarkers to improve prognostication of ACC. Aim of the study was to perform a comparative analysis of DNA-based biomarkers (BM) for prognostic assessment of ACC by evaluating their added value to the established prognostic ...

Background: Combinatory treatments with analogues of incretins might mimic the beneficial effects of bariatric surgery. We could show in the past that a combinatory treatment with PYY 3-36 and liraglutide leads to a similar body weight loss as Roux-en-Y gastric bypass (RYGB). We hypothesize that a combination of semaglutide and a modified PYY 3-36 analogue with increased selectivity for the neuropeptide Y receptor type 2 (NNC0165-1273) exceeds the weight-reducing effects of ba...

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...

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy presenting with an incidence of 1 per million per year and an overall 5-year survival rate under 35%. Currently, curative treatment is limited to full surgical resection, while the adrenolytic drug mitotane remains the only approved medical therapy option leaving a huge demand for innovative therapeutic strategies. Genetic alterations observed in ACC commonly lead to activation of Wnt/β-Catenin signaling most f...

Background: Adrenocortical carcinoma (ACC) is a rare aggressive cancer with limited treatment options for advanced stages. By targeted RNA expression screening, we identified polo-like kinase 1 (PLK1) as one of most overexpressed genes, thus representing a potential drug target for ACC. PLK1 inhibitors are under evaluation in clinical trials for other solid cancers and seem to be more effective in TP53 mutated tumours. The aim of the study was to evaluate PLK1 protein levels i...

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 ...