Endocrine Abstracts

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...

Background: Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in obese individuals. GLP-1 agonists, such as semaglutide, and SGLT-2 inhibitors, such as empagliflozin, are well known to be beneficial in NAFLD, while other incretins, like peptide tyrosine tyrosine 3-36 (PYY3-36), might be also useful for the treatment of NAFLD. We directly compared the effects of semaglutide alone and in combination with peptide tyrosine tyrosine 3-36 (PYY3-36), empagliflozin and...

Background: Bisphenol A (BPA) is known to act as an endocrine disruptor in different organs. However, its impact on adrenal gland functionality 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) o...

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...

Background: An activation of the hypothalamic-pituitary-adrenal (HPA) axis is a common observation in obese individuals. GLP-1 agonists, such as semaglutide, and SGLT-2 inhibitors, such as empagliflozin, are well known to be beneficial in obesity, while other incretins, like peptide tyrosine tyrosine 3-36 (PYY 3-36), might be also useful for the treatment of obesity. However, the effect of these substances on the adrenal gland is largely unknown. We directly compared the effec...

Background: The diagnostic workup of primary aldosteronism (PA) is challenging and the current screening tool, aldosterone-renin ratio, is increasingly challenged. Due to interference with immunoassays and the general high variability of plasma aldosterone levels false-positive as well as false-negative results are probably more frequent than previously assumed. Therefore, we aimed at the establishment of a reliable LC-MS/MS method to analyze aldosterone and related steroids i...

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...

Background: The chemokine receptor CXCR4 and its associate receptor CXCR7, that modulates CXCR4 function, have been associated with tumor progression and metastasis in human cancers. In ACC, Ki67 index and ENSAT stage are the most important prognostic parameters.Objective: To assess expression of CXCR4 and CXCR7 in adrenal cancer and correlate results with clinical outcome.Methods: CR expression was assessed by immunohistochemistry...

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...

Background: Adrenocortical tumors consist of benign adenomas (ACA) and highly malignant carcinomas (ACC). Dysregulation of the Notch signalling pathway is implicated in several cancers with oncogenic or tumor suppressor functions. JAG1 is a Notch1 ligand of the Jagged family and a common target gene for Notch and Wnt/β catenin pathways. It has been reported that upregulated expression of JAG1 enhances cell proliferation in ACC.Material and methods: ...