Aberrant cAMP-PKA signaling was first associated with the development CS due to primary bimorphic adrenocortical disease (PBAD) in the rare tumor disorder McCune-Albright syndrome (MAS), which is caused by early embryonic postzygotic somatic activating defects in GNAS, the gene that encodes the α-subunit of the stimulatory G protein (Gsα) (2, 4). Here, GNAS is linked to Cowden syndrome 1.