In our eight cases in which the 11-deoxycortisol response to Metyrapone was poor, despite high ACTH after Metyrapone, only three were after treatment with high doses of GCS, and two were after unilateral adrenalectomy due to hypercortisolemia (the same mechanism of secondary adrenal insufficiency as after GCS). This evidence concerns the gene POMC and adrenal gland hyperfunction.