Endocrine Abstracts

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...

Background and Methods: Corticotropin-independent Cushing’s syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol producing adrenal adenomas is not well understood. Therefore, exome sequencing was performed in 10 cortisol-producing adenomas and recurrent mutations in candidate genes were evaluated in additional 171 patients with adrenocortical tumors. In addition, genome-wide copy number analysis was performed in 35 pati...

Background: The prognosis of adrenocortical carcinomas (ACCs) is heterogeneous. Genome-wide methylation analysis of tumor DNA identified a sub-group of ACCs from the French COMETE network with CpG island hypermethylation evoking a CpG island methylator phenotype (CIMP). These ACCs are associated with a poorer prognosis (Barreau, JCEM 2013).The aim was to validate the prognostic value of CIMP in a large multicentric independent cohort from ENSAT (European...