Most of the reported mutations in ACTH-secreting adenomas alter the amino acid sequence in the 14-3-3 binding site and disrupt the USP8 and 14-3-3 bond, thus un-inhibiting USP8 activity because of increased cleavage of the catalytic domain [9] and/or increased spontaneous enzymatic activity even without such cleavage [7]. This evidence concerns the gene USP8 and adenoma.