Endocrine Abstracts

Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D have been described in 50% of aldosterone producing adenomas (APA). To identify genetic alterations in new genes, we performed whole exome sequencing in 23 patients with APA negative for recurrent mutations in known driver genes. A low number of somatic variations were identified per patient, ranging from 1 to 22. N...

Primary aldosteronism caused by aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia is the most prevalent cause of secondary hypertension. Somatic mutations of KCNJ5, ATP1A1, CACNA1D and ATP2B3 have been shown to be involved in the formation of APA. We studied the immunoexpressions of CYP11B2 and HSD3B2, the rate-limiting enzyme for aldosterone production and the prevalent isoform of β-HSD found in APA respectively, and...

Background: Sporadic aldosterone-producing adenomas (APA) are relevant cause of endocrine related hypertension in Primary Aldosteronism (PA). Next generation sequencing techniques have identified somatic mutations in APA harbored in KCNJ5, ATP1A1, ATP2B3, CACNA1D, CTNNB1 and PRKACA genes. Yet, a number of APA harbor no mutations in candidate genes (designated as wild type, WT) and little is known about genotype/phenotype correlation.Objectives: We invest...

Aldosterone-producing adenomas (APAs) are the most frequent cause of primary aldosteronism (PA). Somatic mutations of KCNJ5, ATP1A1, CACNA1D and ATP2B3 are involved in APAs formation while CTNNB1 and GNAS somatic mutations have been described in both APAs and in cortisol-producing adenomas (CPAs). In contrast, mutations of PRKACA coding for the catalytic subunit of protein kinase A have been yet only identified in ...

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...

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...

Introduction: Cushing’s disease (CD) is caused by pituitary tumors hypersecreting adrenocorticotropin (ACTH). Until now somatic mutations in the 14-3-3 binding domain of Ubiquitin Specific Peptidase 8 gene (USP8) were the only recurring, driver mutations and were described in about 40% of the 446 CD samples that have been analysed wordwide. We wanted to assess if other driver mutations might be the pathogenetic cause of CD in those tumors without USP8 mu...