Endocrine Abstracts

Background: The management of adjuvant mitotane therapy in patients with adrenocortical carcinoma (ACC) is challenging. Plasma mitotane concentrations>14 mg/l have been associated with efficacy in the treatment of advanced ACC; however, data in the adjuvant setting are mixed. Moreover, there is no consensus on how to assess the optimal exposure to mitotane and all the proposed methods have inherent limitations. We have recently proposed a new method analogous to what is es...

Background: Steroid synthesis inhibitors, like metyrapone, osilodrostat, and ketoconazole are used as second-line treatment in all types of endogenous Cushing’s syndrome (CS). However, a direct comparison of these three drugs is missing. This study aimed to compare these drugs in the short-term therapy of CS.Design: Retrospective multicenter study involving 15 European centers.Methods: Patients with CS treated with metyrapone,...

Background: Benign adrenal tumours (AT) can be non-functioning (NFAT) or associated with cortisol excess, as indicated by failure to suppress serum morning cortisol to <50 nmol/l in the 1mg-dexamethasone suppression test (1 mg-DST). The latter group divides into patients with clinically overt signs of cortisol excess (adrenal Cushing’s syndrome, CUSH) and patients lacking CUSH signs (mild autonomous cortisol excess, MACE). Smaller series and a recent meta-analysis rep...

Objective: Urine steroid metabolomics, combining mass spectrometry-based steroid profiling and machine learning, has been described as a novel diagnostic tool for detection of adrenocortical carcinoma (ACC). This proof-of-concept study evaluated the performance of urine steroid metabolomics as a tool for post-operative recurrence detection after microscopically complete (R0) resection of ACC.Methods: 135 ACC patients from 14 clinical centres provided pos...

Objective: Urine steroid metabolomics, combining mass spectrometry-based steroid profiling and machine learning, has been described as a novel diagnostic tool for detection of adrenocortical carcinoma (ACC). This proof-of-concept study evaluated the performance of urine steroid metabolomics as a tool for post-operative recurrence detection after microscopically complete (R0) resection of ACC.Methods: 135 patients from 14 clinical centers provided post-op...

Background: Adrenocortical cancer (ACC) is an aggressive tumour with heterogeneous prognosis. Recently integrated genomics reported distinct genomic alterations: transcriptome “C1A” (high expression of proliferation/cell cycle-related genes) vs “C1B”, “CIMP” (CpG islands hypermethylation) vs “non-CIMP”, chromosome alterations “Noisy” (numerous and anarchic alterations) vs “Chromosomal” (extended patterns of loss of he...

Genetic alterations affecting the PKA/cAMP pathway are commonly found in cortisol-producing adrenocortical adenomas (ACAs), while activating mutations in the gene coding for β-catenin (CTNNB1) have been reported in both adenomas and carcinomas. However, the molecular pathogenesis of most ACAs is still unclear. Aim of the study was a comprehensive genetic characterization of sporadic ACAs and the identification of novel molecular markers involved in adrenal tumori...

Recent pan-genomic analyses of tumor DNA identified specific patterns of DNA methylation –e.g. CpG islands hypermethylation in the promoter regions of genes- as pejorative prognostic markers in adrenocortical cancer (ACC). Integrated genomics clearly shows that ACC with such an hypermethylation belongs to specific subgroups of ACC with increased driver genes alterations and a poor survival.Aim: To confirm the prognostic value of this methylation pat...

Context: Adrenocortical carcinoma (ACC) is an aggressive malignancy with high recurrence rates. Regular post-operative follow-up imaging is essential, but associated with high radiation exposure and frequent diagnostic ambiguity. Urine steroid metabolomics has been described as a novel diagnostic tool for the detection of adrenocortical malignancy. Here we present the first clinical study assessing the performance of this innovative approach in the follow-up of patients with c...

Context: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC) and in clinical use for more than 50 years. Mitotane counteracts both tumour growth and tumoral steroid hormone production but treatment is associated with severe side effects. The molecular mechanism of mitotane is still unknown, which hampers progress in treatment of ACC.Objective: To identify the mechanism of action and molecular target of mitotane.<p class...