The production of cortisol by the adrenal glands is stimulated by ACTH (Adrenal Cortical Tropic Hormone), which is produced by the pituitary gland in the brain. Thus, overproduction of cortisol can be caused by either a tumor in the pituitary gland (Cushing's disease), or in the adrenal glands (Cushing's syndrome). Less commonly, a tumor producing too much ACTH may be found outside of the pituitary gland. In patients with Cushing's disease, the blood levels of both ACTH and cortisol are elevated. In patients with Cushing's syndrome, the blood level of cortisol is increased in the setting of a low level of ACTH. Rarely, adrenocortical cancers may cause Cushing's syndrome.
There is a great deal of variability throughout the day in the amounts of cortisol produced by the adrenal glands. For this reason, the most sensitive test measures the amount of cortisol excreted in the urine over a 24-hour period. A 24 hour free cortisol level greater than 100 µg is diagnostic of Cushing's syndrome. Patients suspected of having Cushing's syndrome will also undergo a dexamethasone suppression test which helps to determine the cause of the increased cortisol production. A CT or MRI scan is used to determine the location of the tumor.
Patients with Cushing's disease typically have benign tumors of the pituitary gland in the brain. These patients are referred to a neurosurgeon for removal of the tumors. If removal of the pituitary tumor and medications fail to control Cushing's disease, removing both adrenal glands may be indicated. In patients with Cushing's syndrome, an adrenalectomy—surgical removal of the adrenal gland—is curative. This operation is usually performed laparoscopically, through several very small incisions.