Question: What is a dexamethasone suppression test and why is it used?

Answer: ACTH is the pituitary hormone which regulates cortisol, the glucocorticoid, that is produced by the adrenal glands. Normally, the pituitary gland decreases or suppresses its output of ACTH when cortisol levels are high; the suppresion of ACTH then results in a return of cortisol levels to normal. Dexamethasone is a potent synthetic glucocorticoid which does not interfere with the measurement of cortisol levels in plasma or in urine. Dexamethasone suppression tests are used to determine whether the increased production of cortisol is caused by Cushing's syndrome or is secondary to other causes such as stress. In addition, the tests can also be useful to distinguish between the different causes of Cushing's.

In pituitary ACTH secreting tumors, the ACTH production by the tumor (and by extension cortisol levels also) can be decreased in part by dexamethasone, but only at higher levels than the normal pituitary cells. In Cushing's syndromes secondary to excess production of ACTH by tumors arising in organs other than the pituitary (ectopic ACTH syndrome), the dexamethasone can usually not suppress the ACTH production by the tumors; however this is not always the case as the ACTH produced by some benign carcinoid tumors of the lung or pancreas can be suppressed by dexamethasone. In Cushing's syndrome secondary to excess cortisol production by adrenal tumors, the ACTH levels are already very low and cannot be suppressed further by dexamethasone; thus cortisol levels do not decrease following dexamethasone administration.

Different dexamethasone tests have been used over the years since their original description by Grant Liddle from Vanderbilt University (Nashville TN) in 1960. The classical test reported by Liddle, uses oral administration of dexamethasone following 2 days of baseline 24 hour urine collections. Dexamethasone is administered at the dose of 0.5 mg every six hours for 48 hours, followed by 2 mg of dexamethasone every 6 hours for a second 48 hour period. Normal individuals will suppress their production of cortisol, as measured by plasma cortisol and urinary levels of its metabolites or free urinary cortisol itself, with the low dose of 2 mg/day (0.5 mg every 6 hours) of dexamethasone. Individuals with Cushing's syndrome do not suppress normally during the low level dexamethasone test. The high dose test (2 mg every 6 hours) is used to distinguish between ACTH-dependent pituitary disease (partial cortisol suppression) and either ACTH-independent adrenal tumors or the secretion of ACTH by ectopic tumors located elsewhere in the body (no suppression).

During the 1980's, more rapid dexamethasone tests were designed. In one commonly employed test, dexamethasone is used at the dose of 1 mg taken at 11 PM or 12 midnight followed by the determination of plasma cortisol on the following morning at 8 AM. Again, patients with Cushing's syndrome do not suppress normally during this low dose test. A short test that can discriminate between pituitary Cushing's disease and other causes of Cushing's syndrome utilizes a dexamethasone dose of 8 mg at 11 PM followed by a measurement of plasma cortisol the following morning. Patients with pituitary Cushing's disease suppress their plasma cortisol by 50% or more following the 8 mg of dexamethasone, whereas patients with other causes of Cushing's syndrome do not usually suppress their plasma cortisol.

More recently, other investigators have used an intravenous infusion of dexamethasone over a period of 4 to 7 hours. This modified test has the advantage of requiring only 24 hours to discriminate between normal individuals and those with Cushing's syndrome. This test is also capable of suggesting whether the cause is pituitary, adrenal, or ectopic in origin.

Dexamethasone suppression tests are not 100% percent precise, but do give good indications. In general, the dexamethasone suppression tests will correctly indicate the presence of Cushing's syndrome in 85-90 % of the cases, and effectively determine the cause (pituitary, adrenal, or ectopic) in 75-90 % of the cases.