POMC and Cushing syndrome due to macronodular adrenal hyperplasia: Both treatment groups showed a reduction in seizures: 43% of the low-dose group and 56% of the high-dose group; however, patients treated with high doses had a higher incidence of agitation, sleep disorders (p = 0.002), and Cushing syndrome (p = 0.04).22Moreover, a retrospective cohort study23showed no difference between low-moderate (40 IU/day) versus high-dose (120 IU/day) natural ACTH, and natural versus synthetic ACTH, after 2 to 3 weeks of treatment.