Surgical management of Cushing's disease: a personal perspective.

One of the rewards of studying Cushing's disease is that the understanding of the stages of these tumors provides insight into what happens during the evolution of all types of pituitary tumors. The evolution of the development of the pseudocapsule at the margin of small adenomas begins to occur at about 2 to 3 mm in diameter, the minimum size at which we can identify them during surgical exploration. Certain advantages derive from removal of pituitary adenomas using the histological pseudocapsule as a surgical capsule and as a defined tissue plane. Other unresolved issues need our focus over the next few years. Surgical success would be enhanced if we had more accurate ways of localizing the very smallest tumors, either before or during surgery, in patients with Cushing's disease and negative MRI. We also need better therapies for tumors that invade the cavernous sinus, and we need to understand the biological basis of invasion in patients who have truly invasive tumors. Finally, it would be rewarding to understand the molecular basis of the relative resistance to negative cortisol feedback characterizing these tumors and why it is linked to tumor formation. We still have much to do.