In summary, persistent, subtle, autonomous ACTH secretion that engenders mild, yet continually elevated levels of cortisol is difficult to diagnose due to the presence of interfering clinical conditions, such as obesity and depression, which are more prevalent in the general population, and heterogeneity in severity or temporal stage of the disease among subgroups of examined patients. This problem can be mitigated by developing a structured and standardized approach to the evaluation of patients who undergo pituitary surgery for CD. This evidence concerns the gene POMC and major depressive disorder.