UFC excretion reflects plasma unbound cortisol that is filtered and excreted by the kidney. This test is extremely sensitive for the diagnosis of Cushing's syndrome because, in 90% of affected patients, the initial UFC level is greater than 50 μg/24 hours when measured by HPLC or mass spectroscopy cortisol assays.
Patients with Cushing's disease usually have UFC levels between 100 and 500 μg/24 hours,
Whereas patients with the ectopic ACTH syndrome and cortisol-secreting adrenal adenomas or carcinomas frequently have UFC levels greater than 500 μg/24 hours.
The normal plasma cortisol level ranges between 8 and 25 μg/dL and declines throughout the day. By , the values are usually less than 5 μg/dL. Most patients with Cushing's syndrome lack this diurnal variation. Thus, although their morning cortisol levels may be normal, their afternoon or evening concentrations are markedly higher.
The overnight dexamethasone suppression test can also be used as a screening test to evaluate patients suspected of having hypercortisolism. Dexamethasone, 1 mg, is given orally at , and plasma cortisol is measured the following morning at . A morning plasma cortisol level greater than 3 μg/dL suggests hypercortisolism. This test is easy and can be performed in an outpatient setting. The test is fairly sensitive, although some pituitary adenomas are very sensitive to dexamethasone and can suppress cortisol production readily in this test. However, the test produces a significant number of false-positive results, especially in obese and depressed patients.
For these reasons, collection of urine for measurement of 24-hour UFC excretion is a better screening test.
In the dexamethasone suppression test (Liddle test), 0.5 mg of dexamethasone is given orally every 6 hours for 2 days, followed by 2 mg of dexamethasone every 6 hours for another 2 days. On the second day of the high dosage of dexamethasone, UFC is suppressed to less than 10% of that of the baseline collection in patients with pituitary adenomas but not in patients with the ectopic ACTH syndrome or adrenal cortisol-secreted tumors. Although the Liddle test is often helpful in establishing the etiology of Cushing's syndrome, it has some disadvantages. The test requires accurate measurement of urine collections, often necessitating inpatient hospitalization. In approximately 50% of patients with bronchial carcinoids causing ectopic ACTH production, cortisol secretion is suppressible by high-dose dexamethasone, which yields a false-positive result. In addition, because patients with Cushing's syndrome are often episodic secretors of corticosteroids, considerable variation in daily UFC excretion can occur and false results can be obtained. Therefore, the Liddle test should be interpreted cautiously and other confirmatory tests should be performed before a patient is sent to surgery.
An overnight high-dose dexamethasone suppression test is helpful in establishing the etiology of Cushing's syndrome. In this test, a baseline cortisol level is measured, and then 8 mg of dexamethasone is given orally at . At the following morning, a plasma cortisol measurement is obtained. Suppression, which would occur in patients with pituitary Cushing's disease, is defined as a decrease in plasma cortisol to less than 50% of the baseline level. Few patients with bronchial carcinoid have been examined, so the suppressibility of these tumors by high-dose overnight dexamethasone is not well established.
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TABLE 35-2 Association between Pathobiology of Causative Agents and Clinical Features in Acute Infectious Diarrhea