Cushing’s syndrome occurs when the body makes too much cortisol. This may be caused by a tumor on the pituitary gland or the adrenal glands, or by taking a high level of cortisol-like medication.

Cortisol helps the body respond to stress, maintain the immune system, blood pressure and cardiovascular function, and convert fat, carbohydrates and proteins into energy. Too much cortisol in the blood over a long period can cause may physical changes, including weight gain in the neck, face and upper body, flushing in the face, easy bruising, purple stretch marks on the abdomen, diabetes, high blood pressure, bone loss, excess facial hair and fewer menstrual periods in women, muscle weakness and infertility. Excess cortisol can also cause cognitive problems (memory, thinking) and depression.

Too much cortisol in the blood may be caused by:

ACTH secreting pituitary tumor (Cushing’s disease). When Cushing’s syndrome is caused by a tumor in the pituitary gland, it is called Cushing’s disease. Small tumors on the pituitary gland, which are usually benign, can cause the adrenal glands to make too much cortisol. While 90 percent of tumors the produce ACTH are located in the pituitary, at times other tumors (usually in the lungs) can also produce too much ACTH and cause Cushing’s syndrome.

Ectopic ACTH syndrome. Tumors (cancerous or noncancerous) may arise outside the pituitary gland and produce ACTH. Tumors in the lungs cause more than half of the cases of ectopic ACTH syndrome.

Cortisol-producing adrenal tumors. In about 10 percent to 15 percent of cases, an abnormality of the adrenal glands (most often an adrenal tumor) causes Cushing’s syndrome. Adrenal tumors are more common in women than men. Most of these cases involve benign tumors of adrenal tissue that release excess cortisol into the blood.

Nodular adrenal hyperplasia. An enlargement of the adrenal gland that causes an overproduction of cortisol.

Cortisol-like medications. Cushing’s syndrome can occur when the body is exposed to higher than normal amounts of cortisol-like drugs for an extended period of time. This can happen when a person takes steroids such as prednisone for an extended period to treat conditions such as asthma or lupus.

Diagnosing Cushing’s syndrome

Because Cushing’s syndrome causes many symptoms, and each person has different symptoms, it can be difficult to diagnose. Froedtert & The Medical College of Wisconsin endocrinologists are experts at interpreting test results to accurately diagnose Cushing’s syndrome. Tests may include blood tests and salivary cortisol tests.

Blood tests measure cortisol levels and evaluate how well the pituitary and adrenal glands are working.

Salivary cortisol tests involve measuring cortisol levels in saliva between 11:00 pm and midnight (people with Cushing’s have an elevated cortisol level late in the evening, when it should otherwise decrease). A person simply places an absorbing material in the mouth to collect saliva for testing. The material is then placed in a small vial and mailed to the lab for analysis. If the test is positive, it is repeated and other tests are done to confirm a Cushing’s diagnosis. Medical College of Wisconsin endocrinologist James Findling, MD, FACP, helped develop this important test in the 1990s.

Other tests for Cushing’s may include:

Inferior petrosal sinus sampling (IPSS), a minimally invasive test that involves collecting a blood sample from the inferior petrosal sinuses (at the base of the skull) and an arm vein. The test is done to determine if ACTH production is related to a pituitary or non-pituitary source. Medical College of Wisconsin endocrinologist James Findling, MD, FACP, developed this test in the last 1970s/early 1980s. today, the test is used across the United States to help diagnose Cushing’s.

Dexamethasone suppression test, which measures the response of the adrenal glands to ACTH. A patient receives dexamethasone, and the patient’s cortisol levels are measured.

Urine cortisol test, which measures the amount of cortisol in urine collected over 24 hours.

Imaging to identify the location of a tumor. Imaging may involve an MRI of the pituitary gland or a CT of the adrenal gland. It a tumor isn’t found in either gland, imaging of the lung may be done to locate a tumor causing Cushing’s.

Teamwork to Treat Cushing’s

When Cushing’s is caused by one or more tumor of the pituitary or adrenal glands, the most effective treatment is surgery to remove the tumor(s). People with Cushing’s syndrome caused by adrenal tumors have a nearly 100 percent cure rate once the tumor(s) are removed. For people with Cushing’s disease caused by pituitary tumors, the cure rate is about 80 percent. After surgery, most symptoms resolve.

Some tumors that cause Cushing’s will recur. When this happens, surgery may be performed again. Radiation therapy may also be used to try to destroy a recurring tumor in the pituitary gland.

If treatments directed at the pituitary fail to provide adequate control of Cushing’s, the patient may then have both adrenal glands removed laparoscopically (minimally invasive surgery). The patient will then require lifelong oral steroid replacement.

If the patient has an adrenal tumor causing Cushing’s syndrome, the initial treatment of choice is laparoscopic removal of the involved adrenal gland.

Currently, there are no FDA approved medications to treat Cushing’s syndrome. Ketoconazole, an anti-fungal medication, used in high doses may be helpful for to lower cortisol levels in some patients. Because this drug has side effects, it should only be used by an experienced endocrinologist.

When Cushing’s syndrome is caused by taking an excessive level of cortisol-like medications, treatment involves symptom relief and medication to help prevent bone loss.

Patients also receive treatment for specific symptoms, such as medication for high blood pressure, diabetes and depression, as well as education for helpful lifestyle changes.

Last Review Date: Aug. 27, 2009