The causes are divided into three categories: iatrogenic, primary, and secondary. Iatrogenic causes are a result of excessive cortisol levels from chronic therapy with glucocorticoids. Approximately 25% of cases have a primary cause of excessive cortisol production from adrenal neoplasms such as adenomas or carcinomas. The tumors usually affect only one adrenal gland, and about 50% are malignant. Even with appropriate treatment, most patients with adrenal carcinoma die within 3 years because of metastases to the liver and lung. Secondary Cushing's syndrome is more common than primary, and bilateral adrenal hyperplasia is the most common secondary condition. It is caused by excessive production of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland.

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