Endocrine Abstracts

Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options.Purpose: To look for new therapeutic approaches issued from the screening for common genetic variants in a large series of advanced ACC.Experimental design: Whole exome sequencing have been performed in 10 advanced (stage III and IV) ACC samples to identify the recurrent variants. The presence and the frequency of most interesting variants ...

Context: Diagnosis announcement of a chronic disease is a crucial moment for patients as well as for their families and an important step of the management of severe conditions like rare endocrine diseases. It is considered as an ‘eternal minute’, marking the end of a time of life when the disease was absent. Little is known on how diagnosis is communicated to patients and families. FIRENDO as defined by the National Plan for Rare Diseases aims at promoting education...

Introduction and rationale: Cushing’s syndrome (CS) is a rare disease with hypercortisolism caused either by ACTH excess from a pituitary or non-pituitary tumor or by an ACTH-independent primary adrenal overproduction of cortisol. It is associated with significant comorbidities potentially lethal: hypertension, diabetes, coagulopathy, cardiovascular disease, infections, and osteoporotic fractures. It is usually managed by surgery and/or medical treatment with steroidogene...

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...

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...