Searchable abstracts of presentations at key conferences in endocrinology

ea0090oc9.4 | Oral Communications 9: Adrenal and Cardiovascular Endocrinology 2 | ECE2023

Recovery of adrenal function after stopping mitotane in patients with adrenocortical carcinoma

Altieri Barbara , Kimpel Otilia , Megerle Felix , Detomas Mario , Chifu Irina , Quinkler Marcus , Matthias Kroiss , Fassnacht Martin

Background: Mitotane is regularly used in patients with adrenocortical carcinoma (ACC) adjuvantly, in patients with high risk of recurrence, and in advanced disease. Multiple effects of mitotane result in adrenal insufficiency in virtually all patients. However, it is unclear how frequently the hypothalamic-pituitary-adrenal (HPA) axis is recovering after treatment discontinuation. Here, we aim to investigate the HPA axis after treatment with mitotane.Me...

ea0090p113 | Endocrine-related Cancer | ECE2023

In silico neoantigen prediction - a forceful avenue to improve immunotherapy in human adrenocortical carcinoma

Landwehr Laura-Sophie , Appenzeller Silke , Olsner Laura , Weigand Isabel , Sbiera Silviu , Fassnacht Martin , Kroiss Matthias

Introduction: Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies and confers a poor prognosis in advanced stages. Effective treatments are lacking. The results of immune checkpoint inhibition were disappointing with few responders only deriving clinical benefit. For the development of novel immunotherapies such as tumor vaccines and T cell-based treatments, target identification is essential. Tumor-specific mutant neoantigens that may be recogn...

ea0049gp121 | Endocrine Tumours | ECE2017

Immunity in adrenocortical carcinoma patients – interplay between anti-cancer immunity and steroid hormones

Sbiera Silviu , Dexneit Thomas , Sbiera Iuliu , Schreiner Jochen , Ronchi Cristina L. , Kroiss Matthias , Fassnacht Martin

Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies. By applying a ‘multiple omics’ approach, we recently identified two distinct subgroups of ACC patients, a good prognosis “immune” and bad prognosis “steroid” phenotype.We hypothesized that the steroid phenotype is associated with glucocorticoid-induced suppression that can be ‘rescued’ by reactivating the immune system using immune...

ea0037ep1125 | Endocrine tumours | ECE2015

Mitotane directly interacts with lipid membranes and alters membrane structure and dynamics

Muller Peter , Theisgen Stephan , Schirbel Andreas , Sbiera Silviu , Haralampiev Ivan , Fassnacht Martin , Huster Daniel , Kroiss Matthias

Context: Mitotane (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]ethane) is the only drug approved for treatment of adrenocortical carcinoma (ACC). Mitotane counteracts both tumor growth and tumoural steroid hormone production but treatment is severely hampered by unfavorable pharmacokinetics and serious side effects. Mitotane is a lipophilic compound and treatment emergent alterations of lipid metabolism are frequently observed. This raises the question whether mitotane d...

ea0070oc1.4 | Adrenal and Cardiovascular Endocrinology | ECE2020

Immune infiltrate and PD-1 / PD-L1 expression in adrenocortical carcinoma: who can predict patients´ outcome?

Landwehr Laura-Sophie , Sbiera Iuliu , Schreiner Jochen , Weigand Isabel , Kroiss Matthias , Fassnacht Martin , Sbiera Silviu

Context: Adrenocortical carcinoma (ACC) are endocrine malignant neoplasms associated with severe aggressiveness. Tumour-related glucocorticoid excess occurs in 60% of patients and is associated with poor prognosis. First clinical trials using immune checkpoint inhibitors are quite unsatisfactory and treatment advancements are urgently needed.Recently, we characterized tumour-infiltrating lymphocytes (TILs) in ACC and identified the detrimental dependency...

ea0070aep83 | Adrenal and Cardiovascular Endocrinology | ECE2020

JIL-O: Establishment of a new steroidogenic human adrenocortical carcinoma cell line

Landwehr Laura-Sophie , Jochen Schreiner , Herterich Sabine , Appenzeller Silke , Fassnacht Martin , Kroiss Matthias , Weigand Isabel

Adrenocortical carcinoma (ACC) is a rare malignancy with heterogeneous but dismal prognosis and despite numerous efforts to improve patient care, effective treatment options are still lacking. ACC in vitro research faces for decades one major obstacle - the unavailability of different ACC cell line models. Here, we present a newly established human ACC cell line that was directly transferred to and now proliferates in cell culture. JIL-O cell line was derived from a p...

ea0056p132 | Endocrine tumours and neoplasia | ECE2018

Role of GLUT-2 expression and MGMT methylation for streptozotocin clinical response in adrenocortical carcinoma

Sbiera Silviu , Maukner Alfred , Kroiss Matthias , Quinkler Marcus , Beuschlein Felix , Rosenwald Andreas , Herterich Sabine , Fassnacht Martin

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...

ea0081p385 | Endocrine-Related Cancer | ECE2022

PD-1 and PD-L1 immune checkpoint expression - the prognostic impact on adrenocortical carcinoma

Landwehr Laura-Sophie , Sbiera Iuliu , Altieri Barbara , Remde Hanna , Kircher Stefan , Sbiera Silviu , Kroiss Matthias , Fassnacht Martin

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...

ea0081p153 | Pituitary and Neuroendocrinology | ECE2022

Subtype-specific pattern of white blood cell differential in endogenous Cushing’s syndrome

Detomas Mario , Altieri Barbara , Chifu Irina , Remde Hanna , Landwehr Laura-Sophie , Sbiera Silviu , Kroiss Matthias , Fassnacht Martin , Deutschbein Timo

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 ...

ea0063gp100 | Adrenal and Neuroendocrine - Basic | ECE2019

Characterization of cell death induced by mitotane in adrenocortical carcinoma cells

Weigand Isabel , Schreiner Jochen , Rohrig Florian , Kiseljak-Vassiliades Katja , Hofner Kerstin , Kendl Sabine , Fassnacht Martin , Sbiera Silviu , Kroiss Matthias

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 ...