Molecular pathogenesis of primary adrenal cushing’s syndrome

Abstract

Recent advances in whole genome/exome sequencing have greatly accelerated our understanding of the molecular mechanisms of tumorigenesis in adrenocortical tumors and hyperplasia. Maintenance of hypercortisolism in primary adrenal Cushing’s syndrome despite the suppression of ACTH secretion by the pituitary results from germline or somatic mutations in a variety of genes as well as from aberrant expression and function of several hormone receptors. This review focuses on novel genetic alterations involved in the cAMP signaling pathway or in armadillo proteins such as ARMC5 and β-catenin as well as on autocrine/paracrine regulatory secretory loops responsible for the abnormal adrenal steroidogenesis in primary adrenal causes of Cushing’s syndrome.