While in Cushing’s syndrome the huge amount of secreted GC overcomes the inactivating activity exerted by the 11BHSD2 enzyme and renders the different 11BHSD1 and GR single nucleotide polymorphisms uninfluential, in mHC these latter factors of GC exposure could become crucial. This evidence concerns the gene NR3C1 and Cushing syndrome due to macronodular adrenal hyperplasia.