Endocrine Abstracts

Introduction: Streptozotocin (SZ) is an active drug for the treatment of advanced adrenocortical carcinoma (ACC) in a minority of patients with an objective response rate of <10%. It has been reported that expression of glucose transporter-2 (GLUT-2) is essential for SZ to enter tumor cells and that high activity of O-6-methylguanine-DNA methyltransferase (MGMT) counteracts the alkylating effect of SZ. Therefore, we aimed to clarify the role of GLUT-2 and MGMT in the respo...

Background: Immune checkpoint therapy response rate in adrenocortical carcinoma (ACC) is only ~15%. Glucocorticoid (GC) secretion is present in ~60% of tumours, associated with adverse outcome and has been associated with an immunologically cold tumoural microenvironment. On the other hand, activation of the Wnt/ß-Catenin pathway has been suggested to contribute to reduced immune infiltration.Aims: First, we aim to improve the understanding of cellu...

Background: Bisphenol A (BPA) acts as an endocrine disruptor in different endocrine systmes. However, its impact on the adrenal cortex and steroidogenesis is largely unknown. This also applies to its substitute substances bisphenol F (BPF) and S (BPS). Therefore, experiments addressing this subject are urgently needed.Methods: The human adrenocortical cell lines NCI-H295R and MUC-1 were treated with increasing concentrations (1 nM–1 mM) of bisphenol...

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy that produces glucocorticoids in 60% of cases causing clinically relevant hypercortisolism. Since, we observed in another study, that shaping these immunosuppressive and life-threatining properties with corticosteroid inhibitors not only led to a glucocorticoid receptor-related downregulation of ROR1 but also to the upregulation of another promising membrane bound oncogenic antigen* (AG), we sought to...

Background: Serum liquid chromatography–tandem mass spectrometry (LC–MS/MS) steroid profiling is used for the diagnosis of adrenocortical carcinoma (ACC). Guidelines recommend endocrine work-up in addition to radiological imaging for follow-up in ACC, but data on this topic are scarce.Aim: To retrospectively investigate an earlier detection of a recurrent or progressive disease by using endocrine follow-up with LC–MS/MS measurements in com...

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 ...