Germline inactivating variants in the PRKAR1A gene (17q22-24 locus) are the main cause of the disease and have been found in more than 70% of patients with familial CNC and PPNAD and more than 70% of patients with familial CNC with almost 100% penetrance [28,30,31]. Here, PRKAR1A is linked to primary pigmented nodular adrenocortical disease.