A higher frequency of PDE11A variants has also been found in patients with CNC, with PDE11A defects being associated with increased development of PPNAD and/or testicular large-cell calcifying Sertoli cell tumors (LCCSCT) in those with PRKAR1A defects, possibly acting as a genetic modifying factor in these patients (71). Here, PRKAR1A is linked to primary pigmented nodular adrenocortical disease.