Endocrine Abstracts

Introduction: Patients with subclinical Cushing’s syndrome (SCS) present with increased cardiovascular morbidity and mortality, however, the beneficial effect of adrenalectomy on cardiovascular risk factors is uncertain.Objective: Systematic meta-analysis to determine the effect of adrenalectomy vs conservative follow-up on cardiovascular risk factors in patients with adrenal tumors and SCS.Methods: We searched 6 databases thr...

Mitotane (o,p’DDD) is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumour. Mitotane is considered an adrenolytic substance, but no information is available regarding distinct steroidogenic effects. Here we carried out steroid metabolomics by gas chromatography/mass spectrometry in 24-hour urine samples from 106 patients with ACC and with samples coll...

Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. Here we investigated the role of circulating cell-free DNA (ccfDNA) in ACC monitoring. We extracted ccfDNA from 1-4 ml EDTA-plasma using the Nonacus Cell3TMXtract or the Qiagen QIAamp MinElute kit and quantified by fluorimeter. We investigated 63 patients with ACC (25M/38F, 52±...

Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited treatment options. We identified polo-like kinase 1 (PLK1) as one of the most overexpressed genes and potential drug target in ACC. PLK1 inhibitors (PLK1i) are under evaluation in clinical trials for other malignancies, being more effective in TP53-mutated tumours. Here we test PLK1i efficacy in four ACC cell lines with different genetic background. Efficacy of three PLK1i (i.e. Volaserti...

Background: Adrenal masses are discovered in 5% of abdominal imaging scans. Work-up aims at exclusion of malignancy and hormone excess. However, estimates of these risks derive from retrospective studies only, mostly small and with significant selection bias.Methods: Prospective multi-centre study (2011–2016) in 14 centres (11 countries) of the European Network for the Study of Adrenal Tumours (ENSAT) with prospective consecutive enrolment of patien...

Background: Adrenal masses are discovered in 5% of cross-sectional abdominal imaging scans. Work-up aims at exclusion of malignancy and hormone excess. However, estimates of these risks presently derive from retrospective studies only, mostly small and with significant selection bias.Methods: Prospective multi-centre study (2011–2016) in 21 centres (17 countries) of the European Network for the Study of Adrenal Tumours (ENSAT) with consecutive enrol...

Context: Differentiating adrenocortical adenoma (ACA) from adrenocortical carcinoma (ACC) represents a continuous challenge in patients with (often incidentally discovered) adrenal masses, with unfavorable sensitivities and specificities provided by tumor size, imaging and even histology. We have previously developed urine steroid metabolomics as a tool for the detection of adrenal malignancy employing gas chromatography mass spectrometry (GC-MS) for the detection of 32 distin...

Introduction: Gas chromatography mass spectrometry (GC-MS) is the gold standard method for urinary steroid profiling. However, GC-MS requires chemical derivatisation, long run times, is labour intensive, expensive, and unsuitable for rapid multi-sample analysis, limiting its use in routine clinical practice. GC-MS urinary steroid metabolomics, the combination of steroid profiling and machine learning (Generalized Matrix Learning Vector Quantization) was shown to have superior ...

Adrenocortical Carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. Here we evaluated a potential new treatment target for ACC, focusing on the mitochondrial NADPH generator Nicotinamide Nucleotide Transhydrogenase (NNT). NNT has a central role within the mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating NNT mutations lead to isolated primary adrenal insufficiency, suggesting a selective vulnerability of adrenoc...

Adrenocortical Carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. Here we evaluated a potential new treatment target for ACC, focusing on the mitochondrial NADPH generator Nicotinamide Nucleotide Transhydrogenase (NNT). NNT has a central role within the mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating NNT mutations lead to isolated primary adrenal insufficiency, suggesting a selective vulnerability of adrenoc...