In Cushing syndrome, the level of corticosteroids is excessive, usually due to overproduction by the adrenal glands.

• Cushing syndrome usually results from a tumor in the pituitary gland that causes the adrenal glands to produce excessive corticosteroids.
• People with Cushing syndrome usually develop excessive fat throughout the torso and have a large, round face and thin skin.
• Doctors measure the level of cortisol to detect Cushing syndrome.
• Surgery or radiation therapy is often needed to remove a tumor.

The adrenal glands may overproduce corticosteroids because of a problem in the adrenal glands or because of too much stimulation from the pituitary gland. An abnormality in the pituitary gland, such as a tumor, can cause the pituitary to produce large amounts of corticotropin, the hormone that controls the production of corticosteroids from the adrenal glands (a condition known as Cushing disease). Tumors outside the pituitary gland, such as small cell lung cancer or a carcinoid tumor in the lungs or elsewhere in the body, can produce corticotropin as well (a condition called ectopic corticotropin syndrome).

Sometimes a noncancerous tumor (adenoma) develops in the adrenal glands, which causes them to overproduce corticosteroids. Adrenal adenomas are extremely common. Half of all people have them by the age of 70. Only a small fraction of adenomas produce excess hormone, however. Cancerous tumors of the adrenal glands are very rare.

Cushing syndrome can also develop in people who must take large doses of corticosteroids because of a serious medical condition. Those who must take large doses have the same symptoms as those who produce too much of the hormone. The symptoms can occasionally occur even if the corticosteroids are inhaled, as for asthma, or are used topically for a skin condition.

Symptoms

Corticosteroids alter the amount and distribution of body fat. Excessive fat develops throughout the torso and may be particularly noticeable at the top of the back. A person with Cushing syndrome usually has a large, round face (moon face). The arms and legs are usually slender in proportion to the thickened trunk. Muscles lose their bulk, leading to weakness. The skin becomes thin, bruises easily, and heals poorly when bruised or cut. Purple streaks that look like stretch marks may develop over the abdomen. People with Cushing syndrome tend to tire easily.

High corticosteroid levels over time raise the blood pressure, weaken bones (osteoporosis), and diminish resistance to infections. The risk of developing kidney stones and diabetes is increased, and mental disturbances, including depression and hallucinations, may occur. Women usually have an irregular menstrual cycle. Children with Cushing syndrome grow slowly and remain short. In some people, the adrenal glands also produce large amounts of androgens (testosterone and similar hormones), leading to increased facial and body hair in women and balding.

Diagnosis

When doctors suspect Cushing syndrome, they measure the level of cortisol, the main corticosteroid hormone, in the blood. Normally, cortisol levels are high in the morning and lower late in the day. In people who have Cushing syndrome, cortisol levels are very high throughout the day.

If the cortisol levels are high, doctors may recommend a dexamethasone suppression test. Dexamethasone suppresses the pituitary gland and should lead to suppression of cortisol secretion by the adrenal glands. If Cushing syndrome is caused by too much pituitary stimulation, the level of cortisol will fall to some extent, although not as much as in people who do not have Cushing syndrome. If Cushing syndrome has another cause, the level of cortisol will remain high. A high corticotropin level further suggests overstimulation of the adrenal gland.

Imaging tests may be needed to determine the exact cause, including a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pituitary or adrenal glands and a chest x-ray or CT scan of the lungs. However, these tests may occasionally fail to find the tumor.

When overproduction of corticotropin is thought to be the cause, blood samples may be taken from the veins that drain the pituitary to see if that is the source.

Treatment

Treatment depends on whether the problem is in the adrenal glands, the pituitary gland, or elsewhere. Surgery or radiation therapy may be needed to remove or destroy a pituitary tumor. Tumors of the adrenal glands (usually adenomas) can often be removed surgically. Both adrenal glands may have to be removed if these treatments are not effective or if no tumor is present. People who have both adrenal glands removed, and many people who have part of their adrenal glands removed, must take corticosteroids for life. Tumors outside the pituitary and adrenal glands that secrete excess hormones are usually surgically removed. Certain drugs, such as metyraponeSome Trade Names
METOPIRONE
or ketoconazoleSome Trade Names
NIZORAL
, can lower cortisol levels and can be used while awaiting more definitive treatment such as surgery.

What Is Nelson Syndrome?
People who have both their adrenal glands removed as treatment for Cushing disease may develop Nelson syndrome. In this disorder, a pituitary tumor develops, producing large amounts of corticotropin, leading to darkening of the skin. The enlarging pituitary tumor may compress nearby structures in the brain, causing headaches and defects in vision. Some experts believe that this compression may be prevented, at least in some people, by radiation therapy to the pituitary gland. If necessary, Nelson syndrome can be treated with radiation therapy or surgical removal of the pituitary gland.

Last full review/revision September 2012 by Ashley B. Grossman, MD, FRCP, FMedSci