High-Dose Test: Standard 2-Day (8-mg) Test


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Subject: High-Dose Test: Standard 2-Day (8-mg) Test

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  • The patient collects at least one baseline 24-hour urine, at 8 am.

  • The patient begins taking 2 mg of dexamethasone orally every 6 hours for a total of 8 doses, usually at 8 am, 2 pm, 8 pm, and 2 am, and the urine collections are continued.

  • In practice, this test is often performed immediately after completing the low-dose dexamethasone suppression test (if the test is positive).

  • The urine collections are assayed for urinary free cortisol and creatinine. In addition, a blood specimen can be collected 6 hours after the last dose of dexamethasone for measurement of cortisol, dexamethasone, and ACTH.

  • This protocol leads to the following values in normal subjects:

    • Urinary free cortisol excretion is <5 μg/24 hours.

    • Serum cortisol and plasma ACTH are low and usually undetectable.

    • Serum dexamethasone ranges from about 8 to 20 ng/mL.

Limitations of All Tests

  • False-positive results may occur in acute and chronic illness, alcoholism, depression, and due to certain drugs (e.g., phenytoin, phenobarbital, primidone, carbamazepine, rifampicin, and spironolactone).

  • Atypical or false-positive responses may occur also due to alcohol, estrogens, birth control pills, pregnancy, obesity, acute illness and stress, and severe depression.

  • Not a good choice for patients in whom CBG levels may be abnormal.

  • Noncompliance (check by measuring plasma dexamethasone).

  • Some patients with large ACTH-producing pituitary adenomas have marked resistance to high-dose dexamethasone suppression. In long-standing cases, nodular hyperplasia of the adrenal may develop causing autonomous cortisol production and resistance to dexamethasone test.

  • No suppression in 80% of cases in ectopic ACTH syndrome or nodular adrenal hyperplasia.

  • Urine cortisol and plasma cortisol are not decreased after high or low doses of dexamethasone in adrenal adenoma or carcinoma or ectopic ACTH syndrome.

  • Patients with psychiatric illness may be resistant and do not reproducibly suppress.