GNAS and Cushing syndrome due to macronodular adrenal hyperplasia: Given the role of GNAS and PDE11A mutations in the development of adrenal hyperplasia and adenomas, as described in detail above, and that GNAS, PDE11A and PRKAR1A all encode essential components of cAMP signaling pathways (Figure 1), it is not completely surprising that Carney Complex patients develop primary pigmented nodular adrenocortical disease, which may cause Cushing syndrome, and cortisol-secreting adrenal adenomas (91).