Genetics of Cushing's Syndrome

The knowledge on the molecular and genetic causes of Cushing's syndrome (CS) has greatly increased in the recent years. Somatic mutations leading to overactive 3',5'-cyclic adenosine monophosphate/protein kinase A and wingless-type MMTV integration site family/beta-catenin pathways are the main molecular mechanisms underlying adrenocortical tumorigenesis. Corticotropinomas are characterized by resistance to glucocorticoid negative feedback, impaired cell cycle control, and overexpression of pathways sustaining adrenocorticotropic hormone secretion. Recognizing the genetic defects behind corticotroph and adrenocortical tumorigenesis proves crucial for tailoring the clinical management of patients with CS and for designing strategies for genetic counseling and clinical screening to be applied in routine medical practice.