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Dexamethasone Suppression Test

The Dexamethasone Suppression Test may be used to screen patients for possible Cushing’s syndrome when this diagnosis seems possible but of low probability.  Several varieties of this test exist, each with a specific protocol. 

  • The Overnight Screening Test is performed by administering 1 mg of dexamethasone orally at 23:00 hours and measuring plasma cortisol at 08:00 the next morning.
  • The Low Dose Test calls for the administration of 0.5 mg of dexamethasone every 6 hours for 48 hours, beginning at 08:00 hours on the first day.  Plasma cortisol is measured at 0, 24 and 48 hours.
  • The classic High Dose Test requires a baseline 08:00 plasma cortisol level and 24 hour urine free cortisol determination followed by administration of 2 mg of dexamethasone every six hours for 48 hours.  This is accompanied by measurement of a 08:00 plasma cortisol level and a 24-hour urine free cortisol level on days two and three.
  • An alternative High Dose protocol administers an 8 mg dose of dexamethasone at 23:00 hours followed by an 08:00 plasma cortisol level, which is compared to a baseline 08:00 plasma cortisol level.

Some medical centers recommend the 1-mg overnight dexamethasone suppression test followed by morning plasma cortisol measurement as the preferred screening test for Cushing syndrome. Normally, the morning cortisol level should be suppressed below 5 ug/dL following the single-dose overnight dexamethasone suppression test. Cortisol levels <5 ug/dL virtually exclude the diagnosis of Cushing syndrome, while levels >10 ug/dL support the diagnosis. Cushing syndrome cannot be excluded if the morning cortisol value falls between 5 and 10 ug/dL. Obesity, depression, alcoholism, high estrogen states, and uremia can cause false positive results. Chronic renal failure and liver failure can cause false negative results. The 1-mg overnight dexamethasone suppression test is most useful in patients with ambiguous urinary free cortisol values. 

Sensitivity for Cushing's syndrome of the Overnight Screening Test is about 98% with an 08:00 plasma cortisol of greater than 7.0 ug/dL. The specificity is approximately 98% in thin, otherwise healthy adults, 87% in obese adults and 77% in chronically ill patients.  False positive tests may occur in patients taking phenytoin or estrogen, and during depression.

A normal response to the Low Dose Test is a 08:00 plasma cortisol at 48 hours of less than 5.0 ug/dL.  Levels greater than this have a sensitivity of 97% and a specificity of 99% for Cushing's syndrome.  Patients taking phenytoin, or patients that are depressed may have positive tests.

Using either of the High Dose Test protocols, the 08:00 plasma cortisol or the urine free cortisol will usually be depressed by at least 50% in patients with Cushing's disease.  The overnight procedure has a reported sensitivity and specificity of 92% and 100% respectively, which is slightly better than the 48-hour test.

Specimen requirement for each cortisol sample is one SST tube of blood.


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