Finally, in a case report of an isolated case of bilateral adrenal hyperplasia, the synergistic action of two variants (p.C21R and p.S247G) on the same allele of MC2R (encoding the melanocortin 2 receptor/ACTH receptor) resulted in autonomous cortisol secretion via constitutive activation of the cAMP/PKA pathway (86). This evidence concerns the gene MC2R and congenital adrenal hyperplasia.