Diseases of the Adrenal Cortex: Cushing's Syndrome

This page contains information that assumes you have read our introduction to the adrenal gland page. If not, go there first. Remember, the adrenal gland has a center gland (medulla) that produces adrenaline, and an outer gland (the cortex) that produces several hormones, such as cortisol an aldosterone. This page is about cortisol overproduction by the adrenal cortex.

In 1932, a physician named Harvey Cushing described eight patients with central body obesity, glucose intolerance, hypertension, excess hair growth, osteoporosis, kidney stones, menstrual irregularity, and emotional liability. It is now known that these symptoms characterize Cushing's syndrome, which is the result of excess production of cortisol by the adrenal glands.

Cortisol is a powerful steroid hormone, and excess cortisol has detrimental effects on many cells throughout the body.  Keep in mind that Cushing's syndrome is rare, occurring in only about 10 patients per one million. On the other hand, simple obesity can be associated with some of these symptoms in the absence of an adrenal tumor; this is related to the slightly different mechanism by which normally produced steroids are metabolized by individuals who are obese. Note: The most common cause of excess steroids in the blood and its side effects, however, is long-term use of steroid medications for other disorders.

Since cortisol production by the adrenal glands is normally under the control of the pituitary, overproduction can be caused by a tumor in the pituitary or within the adrenal glands themselves. When a pituitary tumor secretes too much ACTH (Adrenocorticotropic Hormone), it simply causes the otherwise normal adrenal glands to produce too much cortisol. This type of Cushing's syndrome is termed Cushing's Disease and it is diagnosed like other endocrine disorders (by measuring hormone production). In this case, serum cortisol will be elevated, and serum ACTH will also be elevated.

When the adrenal glands develop a tumor, like any other endocrine gland, they usually produce excess amounts of the hormone normally produced by these cells. If the adrenal tumor is composed of cortisol-producing cells, excess cortisol will be produced. Under these conditions, the normal pituitary will sense the excess cortisol and will stop making ACTH in an attempt to slow the adrenal down. In this manner, physicians can readily distinguish whether excess cortisol is the result of a pituitary tumor or an adrenal tumor.

Even more rare is when excess ACTH is produced somewhere other than the pituitary. This is extremely uncommon, but certain lung cancers can produce ACTH, and patients develop Cushing's syndrome in the same way as if the ACTH was coming from the pituitary.

Causes of Cushing's Syndrome

ACTH Dependent (80%)

• Pituitary tumors (60%)
• Lung cancers (5%)

ACTH Independent (20%)

• Benign adrenal tumors (adenoma) (25%)
• Malignant adrenal tumors (adrenal cell carcinoma) (10%) [new page on this topic]

Testing for Cushing's Syndrome
The most sensitive test to check for the possibility of this disease is to measure the amount of cortisol excreted in the during during a 24-hour period. Cortisol is normally secreted in different amounts during the day and night, so this test usually will be repeated once or twice to eliminate the variability that is normally seen. This normal variability is why simply checking the amount of cortisol in the blood is not a very reliable test. A 24-hour free cortisol level greater than 100 ug is diagnostic of Cushing's syndrome.

The second test that helps confirm this diagnosis is the suppression test which measures the cortisol secretion following the administration of a powerful synthetic steroid that will shut down steroid production in everybody with a normal adrenal gland. Subsequent tests will distinguish whether the disease is due to an ACTH dependent or independent cause.

Invariably, once the diagnosis is made, patients will undergo a CT scan (or possibly an MRI or ultrasound) of the adrenal glands to look for tumors in one or both of them (more information on adrenal x-ray tests on another page). If the laboratory test suggest a pituitary origin, a CT or MRI of the brain (and possibly of the chest as well) will be performed.

Treatment of Cushing's Syndrome
Obviously, the treatment of this disease depends on the cause. Pituitary tumors are usually removed surgically and often treated with radiation therapy. Neurosurgeons and some ENT surgeons specialize in these tumors. If the cause is determined to be within a single adrenal gland, this is treated by surgical removal. If the tumor has characteristics of cancer on any of the x-ray tests, then a larger, conventional operation is in order. If a single adrenal gland possesses a small, well-defined tumor, it can usually be removed by the new technique of laparoscopic adrenalectomy.