Endocrine Abstracts

Background: Genetic alterations underlying the pathogenesis of autonomous cortisol secretion and early adrenocortical tumorigenesis have been identified in 40% of adrenocortical tumors (ACT). Nonetheless, the molecular events leading to development of ACT and steroid secretion remain obscure for a large proportion of patients.Aim: Aims of our study were to investigate the relationship between transcriptome profile and genetic background in a large series...

Background: The human cytochrome P450 (CYP) 2W1 is involved in the metabolism of several endogenous substrates, including lysophospholipids and fatty acids. Using a polyclonal antibody, we previously demonstrated a high CYP2W1 immunoreactivity in adrenocortical tumors, particularly in those secreting steroids. The aim of the study was to better elucidate the relationship between CYP2W1 and steroid secretion in adrenocortical carcinoma (ACC) H295R cell line and in a larger seri...

Context: Primary aldosteronism (PHA) is the most common cause of secondary hypertension. Distinguishing unilateral (UAH) from bilateral (BAH) and other causes of PHA is one of the greatest challenges in the diagnostic process. Adrenal venous sampling (AVS) is widely considered to be the gold standard for subtype differentiation.Methods: Technical and diagnostic outcome of AVS was analysed retrospectively in 59 patients with PHA who underwent AVS at the U...

Adrenocortical carcinoma (ACC) is a rare disease with poor prognosis. Accordingly, in many cases, the attending doctors have no previous experience with the disease. The aim of our study was to evaluate the quality of care in a large number of patients with ACC in Germany. Data from 263 adult patients of the German ACC registry were analyzed with regard to the following parameters: time to diagnosis, hormonal assessment, imaging, histopathological documentation, follow-up. The...

Background: Adrenal masses are discovered in 5% of abdominal imaging scans. Accuracy of currently available imaging tests to diagnose malignancy is poor. In a proof-of-concept study (JCE&M 2011;96(12):3775-84), we had demonstrated 90% sensitivity and specificity in detecting adrenocortical carcinoma (ACC) for urine steroid metabolomics, the combination of mass spectrometry-based steroid profiling and machine learning-based data analysis. This diagnostic performance is supe...

Adrenocortical carcinoma (ACC) has heterogeneous prognosis and no effective targeted therapies. Pan-genomic studies identified complex molecular patterns related to outcome. Our study aimed at identification of an ‘easy-to-apply’ molecular signature for better personalized prognostic stratification. A total of 107 ACC patients were enrolled. Clinical/histopathological parameters of prognostic relevance were evaluated. Targeted molecular analysis was performed on DNA ...

The cytochrome P450 2W1 (CYP2W1) is an orphan enzyme able to activate anticancer pro-drugs and to metabolise endogenous substances as fatty acids and lysophospholipids. Aim of the study was to evaluate the frequency of CYP2W1 polymorphisms in patients with adrenocortical carcinoma (ACC) and correlate it with the sensitivity to mitotane, which represents the only approved drug for the treatment of advanced ACC.Methods: A multicenter retrospective study in...

Recently, somatic, heterozygous mutations in the gene encoding the deubiquitinase USP8 have been identified in 30–60% of corticotroph tumors. These mutations were found to hinder binding of 14-3-3 proteins, increasing its deubiquitinating activity. One substrate is Epidermal Growth Factor Receptor (EGFR), USP8 triggers EGFR recycling and increased EGFR signaling. However, tumors harboring mutations in USP8 are smaller than WT tumors, raising the debate if EGFR, as a poten...

BackgroundAdrenocortical Carcinoma (ACC) is a rare aggressive cancer with a heterogeneous behaviour. Disease surveillance relies on frequent imaging, which has limited sensitivity and results in significant radiation exposure. Aim of the study was to investigate the role of circulating cell-free DNA (ccfDNA) as a biomarker for prognostication and disease monitoring in ACC.MethodsccfDNA was extracted from 1&#8...

BackgroundMitotane represents the first-line medical treatment in most patients with adrenocortical carcinoma (ACC). Although adverse effects (AEs) due to mitotane are known to be frequent and may limit treatment, few systematic data are available. Aim of the study was to evaluate the AEs in ACC patients treated with mitotane monotherapy.MethodsA retrospective multicenter study including 311 ACC patients (M:F...