~ Cushing's Syndrome ~ Note: this page contains information which 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) which produces adrenaline, and an outer gland (the cortex) which produces several hormones such as cortisol an aldosterone. This page is about cortisol overproduction by the adrenal cortex.

In 1932, a physician by the name of 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 are 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. Although some of these symptoms are common by themselves, the combination of these suggests that a workup for this disease may be in order. Keep in mind that Cushings syndrome is rare, occurring in only about 10 patients per one million population. 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 (like the thyroid gland), overproduction can be caused by a tumor in the pituitary or within the adrenal glands themselves. When a pituitary tumor secretes too much ACTH (Adrenal Cortical Tropic Hormone), it simply causes the otherwise normal adrenal glands to produce too much cortisol. This type of Cushings syndrome is termed "Cushings Disease" and it is diagnosed like other endocrine disorders by measuring the appropriateness of hormone production. In this case, serum cortisol will be elevated, and, serum ACTH will be elevated at the same time.

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 which can be measured in the blood. 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 (but placed here for completion sake) is when excess ACTH is produced somewhere other than the pituitary. This is extremely uncommon, but certain lung cancers can make ACTH (we don't know why) and the patients develop Cushings Syndrome in the same way they do as if the ACTH was coming from the pituitary.

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]

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 time 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 which 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 Cushings syndrome. The second test which helps confirms this diagnosis is the suppression test which measures the cortisol secretion following the administration of a powerful synthetic steroid which 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.

Obviously, the treatment of this disease depends upon 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.



More about X-ray Tests for Adrenal Tumors