Adrenolytic therapy

Abstract

In hypercortisolism, adrenolytic therapy can be used diagnostically, as medical management prior to definitive therapy, or as adjunctive therapy for adrenocortical disease in which surgery has not led to a cure. The commonly used agents are metyrapone, ketoconazole, RU 486, octreotide, and mitotane. Metyrapone effectively lowers cortisol levels in Cushing disease and in patients with hypercortisolism secondary to ectopic corticotropin syndrome. Mitotane causes adrenal atrophy, but its use at effective doses is often limited by gastrointestinal side effects. For these reasons its use is mainly restricted to management of adrenocortical carcinoma. The outlook for adrenocortical carcinoma remains poor, but recent publications have reported the use of two new agents, suramin and gossypol which, after further trials and dose adjustments and use in combination therapy, may have a role. With careful diagnostic assessment and follow-up, patients with Cushing disease should now have good outcomes with the available surgical and medical strategies. Most patients with ectopic adrenocorticotropic hormone syndrome can have their hypercortisolism controlled with drugs while other anticancer strategies are used for the primary disease. In contrast, management of adrenocortical carcinoma is still most unsatisfactory and further cooperative trials of chemotherapeutic agents such as etoposide, cisplatin, and doxorubicin are needed.