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December 5, 1977

Mitotane: Spironolactone Antagonism in Cushing's Syndrome

JAMA. 1977;238(23):2527. doi:10.1001/jama.1977.03280240073028

CUSHING'S syndrome is usually treated surgically when it is associated with pituitary-dependent adrenocortical hyperplasia or an adrenal adenoma. However, the patient's general condition may exclude a surgical approach, and in these cases as well as in certain instances of Cushing's syndrome due to metastatic adrenal carcinoma of ectopic adrenocorticotropic hormone (ACTH) production, medical treatment has a place. The drugs available include mitotane, aminoglutethimide, and metyrapone; more recently, successful treatment of adrenocortical hyperplasia with cyproheptadine hydrochloride has been reported.

Mitotane and aminoglutethimide have been the most commonly used, but both have a high incidence of adverse reactions.1 Only mitotane leads to permanent destruction of the adrenal cortex. Spironolactone is commonly used in the management of the hypokalemia of Cushing's syndrome, but in the case we are presenting, it is suggested that this drug blocks the action of mitotane.

Report of a Case  A 65-year-old woman with features of florid Cushing's