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Neurosurg Focus. 2007;23(3):E10.

Medical management of Cushing disease.

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Department of Neurological Surgery, The Feinberg School of Medicine and McGaw Medical Center, Northwestern University, Chicago, Illinois, USA.


Although transsphenoidal excision of the adrenocorticotropic hormone (ACTH)-producing neoplasm is often the treatment of choice in patients with Cushing disease, medical management is itself a useful preoperative temporizing measure, an option for long-term management in nonsurgical candidates, and an option for patients in whom surgery and/or radiotherapy have failed. Three pathophysiologically based approaches exist in the research literature--neuro-modulation to limit ACTH levels, adrenal enzyme inhibition, and glucocorticoid receptor antagonism. Unfortunately, the neuromodulatory approach involving agents such as bromocriptine, cyproheptadine, octreotide, and valproate has yielded only suboptimal results. Glucocorticoid receptor antagonism remains in its infancy but may overall be limited by side effects and a resultant increase in ACTH and cortisol levels. Adrenal enzyme inhibitors, however, offer substantial future promise in the management of Cushing disease but are limited by the potential need to use them indefinitely and by dose-tolerance effects. Although etomidate is a potential intravenous alternative for acute cortisol level control, ketoconazole has shown efficacy in the long-term treatment of patients with the disease. Metyrapone and/or aminoglutethimide can be added to ketoconazole if additional control is needed. If success is still not achieved, the potent adrenolytic agent often used for adrenocortical carcinomas, mitotane, is another alternative.

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