Dexamethasone Suppression Test is based on pituitary Adrenocorticotropic Hormone (ACTH) secretion being dependent on the plasma cortisol feedback mechanism. When blood Cortisol Levels increase, the production of ACTH is suppressed. And vice versa, when blood Cortisol Levels decrease, the production of ACTH is stimulated. Dexamethasone is a synthetic steroid which suppress ACTH secretion the same way to Cortisol does. Under normal circumstances this results in reduced stimulation to the adrenal glands and ultimately a drop of 50% or more in plasma cortisol and 17-OCHS levels. This important feedback system does not function properly in patients with Cushing syndrome.
In Cushing syndrome caused by bilateral adrenal hyperplasia (Cushing disease), the pituitary gland is reset upward and responds only to high plasma levels of cortisone and steroids. In Cushing syndrome caused by adrenal adenoma or cancer (which acts autonomously), cortisol secretion will continue despite a decrease in ACTH. When Cushing syndrome is caused by an ectopic ACTH-producing tumor (as in lung cancer), that tumor is also considered autonomous and will continue to secrete ACTH despite high cortisol levels. Again, no decrease occurs in plasma cortisol. Knowledge of the following defects in the normal cortisol-ACTH feedback system is the basis for understanding the Dexamethasone Suppression Test:
Cushing Syndrome Caused by Bilateral Adrenal Hyperplasia
Low dose: no change
High dose: >50% reduction of plasma cortisol and 17-OCHS levels
Cushing Syndrome Caused by Adrenal Adenoma or Carcinoma
Low dose: no change
High dose: no change
Cushing Syndrome Caused by Ectopic ACTH-Producing Tumor
Low dose: no change
High dose: no change
The Dexamethasone Suppression Test also may identify depressed persons likely to respond to electroconvulsive therapy or antidepressants rather than to psychologic or social interventions. ACTH production will not be suppressed after administration of low-dose Dexamethasone in these patients.
The Prolonged Dexamethasone Suppression Test can be performed over a 6-day period on an outpatient basis. The following steps summarize the important actions performed during this procedure:
- A baseline 24-hour urine collection for corticosteroids is obtained.
- Blood is collected for determination of baseline plasma Cortisol Levels if indicated. As well 24-hour urine specimens are collected daily over a 6-day period. Because 6 continuous days of urine collections are needed, no urine specimens are discarded except for the first voided specimen on day 1, after which the collection begins. The specimens should be refrigerated or kept on ice during the collection period and the creatinine content is measured in all the 24-hour urine collections to demonstrate their accuracy and adequacy.
- On day 3, a low dose of Dexamethasone is administered by mouth.
- On day 5, a high does of Dexamethasone is administered by mouth. The Dexamethasone can be given with milk or an antacid to prevent gastric irritation.
Unlike the Prolonged Dexamethasone Suppression Test, the Rapid Dexamethasone Suppression Test is easily and quickly performed and is also used primarily as a screening test to diagnose Cushing Syndrome. However, the Rapid Dexamethasone Suppression Test is less accurate and less informative than the prolonged Dexamethasone Suppression Test, but when its results are normal, the diagnosis of Cushing syndrome can safely be excluded. The ease with which the rapid Dexamethasone Suppression Test can be performed makes it useful in clinical medicine. The following is a summary of the important steps performed during the Rapid Dexamethasone Suppression Test which should demonstrate how simple it is compared to the Prolonged Dexamethasone Suppression Test:
- A dose of Dexamethasone is given to the patient by mouth at 11 PM. The dose should be administered with milk or an antacid to prevent gastric irritation.
- A good night’s sleep is necessary since Cortisol Levels are sensitive to the patient state of resting or tiredness. Sedative/hypnotics are used only if absolutely necessary.
- At 8 AM the next morning, blood is drawn for determination of the plasma cortisol level before the patient arises.
- If no cortisol suppression occurs after administration of the dose of Dexamethasone, a higher dose is administered to suppress ACTH production. This is referred to as the Overnight 8-mg Dexamethasone Suppression Test. Patients with adrenal hyperplasia will suppress. Patients with adrenal or ectopic tumors will not suppress.
Normal Cortisol Levels of the Dexamethasone Suppression Test
Expected values (normal)
After Low Dose is given on day 3: More than 50% reduction of plasma Cortisol Levels and 17-hydroxycorticosteroid (17-OCHS) levels
After High Dose is given on day 5: More than 50% reduction of plasma Cortisol Levels and 17-OCHS levels
Normal: nearly zero Cortisol Levels.
Causes of Dexamethasone Suppression Test False Indications
- Physical and emotional stress can elevate ACTH release and obscure interpretation of test results. Stress is stimulatory to the pituitary, which thereby secretes ACTH.
- Drug’s that can affect test results include Barbiturates, Estrogens, Oral Contraceptives, Phenytoin (Dilantin), Spironolactone (Aldactone), Steroids, and Tetracyclines.
Causes of Cushing Syndrome
When Cortisol Levels and 17-hydroxycorticosteroid Levels don’t drop after performing the Dexamethasone Suppression Test, this indicates that the production of ACTH is not suppressed by the Dexamethasone dose/doses. When ACTH production doesn’t respond to Dexamethasone, this would be an indication of Cushing Syndrome (Adrenal Hyperfunction). Cushing Syndrome can be a result of the following diseases:
- When ACTH is produced without regard to the inhibitory feedback mechanism that normally exists. This is a result of neoplastic overproduction of ACTH in the pituitary or elsewhere in the body by an ACTH-producing cancer. ACTH is not suppressed. As a result, cortisol is not suppressed. This happens with patient who have Cushing Disease or Ectopic ACTH-producing Tumors.
- Adrenal Adenoma or Adrenal Carcinoma: Neoplasms of the adrenal glands are not sensitive to the inhibitory feedback mechanism that normally exists. Therefore ACTH will be suppressed by the Dexamethasone dose, but cortisol production (the end point of the test) is not.
- Bilateral Adrenal Hyperplasia: The inhibitory feedback mechanism that normally exists in the pituitary-adrenal system is blunted. Therefore at low dexamethasone doses no change in cortisol production is seen. At high dexamethasone doses, however, the ACTH and subsequently cortisol are suppressed.
- Mental Depression: ACTH is not suppressed in individuals likely to require electroconvulsive or medicinal therapy for their depression.