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Cushing's Syndrome (cont.)

How is Cushing's syndrome diagnosed?

Diagnosis is based on a review of the patient's medical history, physical examination and laboratory tests. Often x-ray exams of the adrenal or pituitary glands are useful for locating tumors. These tests help to determine if excess levels of cortisol are present and why.

24-Hour Urinary Free Cortisol Level

This is the most specific diagnostic test. The patient's urine is collected over a 24-hour period and tested for the amount of cortisol. Levels higher than 50-100 micrograms a day for an adult suggest Cushing's syndrome. The normal upper limit varies in different laboratories, depending on which measurement technique is used.

Once Cushing's syndrome has been diagnosed, other tests are used to find the exact location of the abnormality that leads to excess cortisol production. The choice of test depends, in part, on the preference of the endocrinologist or the center where the test is performed.

Dexamethasone Suppression Test

This test helps to distinguish patients with excess production of ACTH due to pituitary adenomas from those with ectopic ACTH-producing tumors. Patients are given dexamethasone, a synthetic glucocorticoid, by mouth every 6 hours for 4 days. For the first 2 days, low doses of dexamethasone are given, and for the last 2 days, higher doses are given. Twenty-four hour urine collections are made before dexamethasone is administered and on each day of the test. Since cortisol and other glucocorticoids signal the pituitary to lower secretion of ACTH, the normal response after taking dexamethasone is a drop in blood and urine cortisol levels. Different responses of cortisol to dexamethasone are obtained depending on whether the cause of Cushing's syndrome is a pituitary adenoma or an ectopic ACTH-producing tumor.

The dexamethasone suppression test can produce false-positive results in patients with depression, alcohol abuse, high estrogen levels, acute illness, and stress. Conversely, drugs such as phenytoin and phenobarbital may cause false-negative results in response to dexamethasone suppression. For this reason, patients are usually advised by their physicians to stop taking these drugs at least one week before the test.

CRH Stimulation Test

This test helps to distinguish between patients with pituitary adenomas and those with ectopic ACTH syndrome or cortisol-secreting adrenal tumors. Patients are given an injection of CRH, the corticotropin-releasing hormone which causes the pituitary to secrete ACTH. Patients with pituitary adenomas usually experience a rise in blood levels of ACTH and cortisol. This response is rarely seen in patients with ectopic ACTH syndrome and practically never in patients with cortisol-secreting adrenal tumors.

Direct Visualization of the Endocrine Glands (Radiologic Imaging)

Imaging tests reveal the size and shape of the pituitary and adrenal glands and help determine if a tumor is present. The most common are the CT (computerized tomography) scan and MRI (magnetic resonance imaging). A CT scan produces a series of x-ray pictures giving a cross-sectional image of a body part. MRI also produces images of the internal organs of the body but without exposing the patient to ionizing radiation.

Imaging procedures are used to find a tumor after a diagnosis has been established. Imaging is not used to make the diagnosis of Cushing's syndrome because benign tumors, sometimes called "incidentalomas," are commonly found in the pituitary and adrenal glands. These tumors do not produce hormones detrimental to health and are not removed unless blood tests show they are a cause of symptoms or they are unusually large. Conversely, pituitary tumors are not detected by imaging in almost 50 percent of patients who ultimately require pituitary surgery for Cushing's syndrome.

Petrosal Sinus Sampling

This test is not always required, but in many cases, it is the best way to separate pituitary from ectopic causes of Cushing's syndrome. Samples of blood are drawn from the petrosal sinuses, veins which drain the pituitary, by introducing catheters through a vein in the upper thigh/groin region, with local anesthesia and mild sedation. X-rays are used to confirm the correct position of the catheters. Often CRH, the hormone which causes the pituitary to secrete ACTH, is given during this test to improve diagnostic accuracy. Levels of ACTH in the petrosal sinuses are measured and compared with ACTH levels in a forearm vein. ACTH levels higher in the petrosal sinuses than in the forearm vein indicate the presence of a pituitary adenoma; similar levels suggest ectopic ACTH syndrome.

The Dexamethasone-CRH Test

Some individuals have high cortisol levels, but do not develop the progressive effects of Cushing's syndrome, such as muscle weakness, fractures and thinning of the skin. These individuals may have Pseudo Cushing's syndrome, which was originally described in people who were depressed or drank excess alcohol, but is now known to be more common. Pseudo Cushing's does not have the same long-term effects on health as Cushing's syndrome and does not require treatment directed at the endocrine glands. Although observation over months to years will distinguish Pseudo Cushing's from Cushing's, the dexamethasone-CRH test was developed to distinguish between the conditions rapidly, so that Cushing's patients can receive prompt treatment. This test combines the dexamethasone suppression and the CRH stimulation tests. Elevations of cortisol during this test suggest Cushing's syndrome.

Some patients may have sustained high cortisol levels without the effects of Cushing's syndrome. These high cortisol levels may be compensating for the body's resistance to cortisol's effects. This rare syndrome of cortisol resistance is a genetic condition that causes hypertension and chronic androgen excess.

Sometimes other conditions may be associated with many of the symptoms of Cushing's syndrome. These include polycystic ovarian syndrome, which may cause menstrual disturbances, weight gain from adolescence, excess hair growth and sometimes impaired insulin action and diabetes. Commonly, weight gain, high blood pressure and abnormal levels of cholesterol and triglycerides in the blood are associated with resistance to insulin action and diabetes; this has been described as the "Metabolic Syndrome-X." Patients with these disorders do not have abnormally elevated cortisol levels.

Medically Reviewed by a Doctor on 4/15/2014

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Source: MedicineNet.com
http://www.medicinenet.com/cushings_syndrome/article.htm

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