Our work, taken together with that of Lee 8 and Schwartz 13, also suggests that the L205R‐PKACα mutation causes ACTH‐independent Cushing's syndrome through a change of substrate specificity and not simply constitutive activation of the L205R gain‐of‐function mutant kinase. This evidence concerns the gene PRKACA and Cushing syndrome due to macronodular adrenal hyperplasia.