Endocrine Abstracts

Recent studies have reported a high prevalence of USP8 mutations in corticotroph adenomas causing Cushing’s disease. Nelson’s syndrome is a potentially life-threatening complication of bilateral adrenalectomy in patients with refractory Cushing’s disease that is caused by the development of an ACTH-secreting tumor in the pituitary gland. Whether USP8 alterations are also present in Nelson’s tumors has not been studied in detail so far....

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...

We have recently reported that somatic mutations in the ubiquitin-specific protease 8 (USP8) are present in corticotropinomas of patients with Cushing’s disease and that these mutations reduced the interaction with 14-3-3. Mutant USP8 exhibited higher deubiquitination activity and potentiated EGFR-induced POMC expression (Reincke et al., Nat Genet 2014). To further study the prevalence of these mutations, we have analyzed 134 ACTH-producing corticotropin...

Introduction: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often an incidental finding, but may be diagnosed in patients with Cushing’s syndrome. We have recently identified germline mutations in the armadillo repeat containing 5 gene (ARMC5) in AIMAH patients, associated with somatic second hits specific of each AIMAH nodule ( Assié et al, NEJM, 2013). The aim is to characterize the prevalence of ARMC5 mutations in AIMAH patients and the gen...

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...

Background: Adrenocortical carcinoma (ACC) has an aggressive but heterogenous behaviour. ENSAT stage and Ki67 proliferation index are used to predict clinical outcome but are limited in distinguishing patients with best outcome. We aimed to validate the prognostic role of clinical and histopathological parameters alone or combined by applying a previously proposed points-based score (mGRAS, Lippert JCEM 2018) to a large multicentre cohort of ACC patients.<p class="abstext"...

Introduction: Carney Complex (CNC) is a rare genetic syndrome, with multiple endocrine and non-endocrine neoplasia, mostly due to inactivating mutations of the PRKAR1A gene. CNC has a wide spectrum of manifestations : most frequently skin lesions, cardiac myxomas and primary pigmented nodular adrenocortical dysplasia (PPNAD), but also thyroid nodules, schwannomas, breast tumors (mainly myxoid fibroadenomas and ductal adenomas)… The present study was designed to ...