The Medical Treatment of Cushing's Syndrome

WITH the advent of synthetic glucocorticoids in the late 1940s, adrenalectomy ushered in the modern era of treatment for Cushing's syndrome. Nearly two decades later, the development of transsphenoidal microsurgical techniques allowed the treatment of Cushing's disease with preservation of anterior pituitary function. Medical treatment for hypercortisolism has also progressed during this time. In the 1950s and 1960s, steroidogenic blocking agents, metyrapone and aminoglutethimide, and the adrenolytic agent, mitotane, first achieved use, later to be joined by the imidazole derivative, ketoconazole. As understanding of ACTH neuroregulation advanced in subsequent decades, agents such as bromocriptine, cyproheptadine, and valproate achieved some clinical use. Most recently, a different class of agent, the steroid receptor antagonist RU-486, has been added to the list of potential therapeutic agents. Although medical therapies for Cushing's syndrome have proliferated, no single agent has yet achieved widespread clinical use compared to surgical therapy. The purpose of this paper is to review clinical studies of the pharmacotherapy of Cushing's syndrome, and to consider the indications for medical therapy in light of accumulated experience with medical, surgical, and radiation therapy.