Detection of new potentially pathogenic mutations in two patients with primary pigmented nodular adrenocortical disease (PPNAD) - case reports with literature review

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare form of ACTH-independent Cushing's syndrome (CS). Half of patients with PPNAD are sporadic cases and the other half familial. We present two patients with PPNAD confirmed by genetic analysis. In both patients there were no abnormal findings on diagnostic imaging of both adrenals and heart. Patients underwent bilateral two-stage adrenalectomy. Histopathological examination confirmed PPNAD. Genetic testing showed the following mutations in the PRKAR1A gene coding for the regulatory subunit type 1A of the protein kinase A enzyme: c.125dupG (patient 1) and c.15dupT (patient 2). Both these defects lead to inactivation of the PRKAR1A protein and are consequently causative of PPNAD in these patients. The novel mutations presented in this article are considered to be pathogenic for PPNAD.