Dexamethasone Suppression Test 

Updated: Nov 21, 2014
  • Author: Georges Elhomsy, MD, ECNU, FACE; Chief Editor: Eric B Staros, MD  more...
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Reference Range

The 2 types of dexamethasone suppression tests are high-dose suppression test and low-dose suppression test. Both tests can be performed either by overnight suppression or by the standard 2-day suppression.

The reference ranges for the low-dose dexamethasone suppression tests are as follows:

  • Overnight dexamethasone suppression test: Serum cortisol less than 1.8 mcg/dL (< 50 nmol/L)
  • Standard 2-day dexamethasone suppression test: Serum cortisol less than 1.8 mcg/dL (< 50 nmol/L)

The reference ranges for the high-dose dexamethasone suppression tests are as follows:

  • Overnight dexamethasone suppression test: Decrease of more than 50% in serum cortisol
  • Standard two-day dexamethasone suppression test: Decrease of more than 50% in serum cortisol or a decrease of more than 50% in 24-hour urinary free cortisol
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Interpretation

Cushing syndrome encompasses all causes of glucocorticoid excess, whereas Cushing disease is reserved only for pituitary-dependent Cushing syndrome.

Low-dose dexamethasone suppression test

Suppression is absent in Cushing syndrome.

False-positive results can occur in the following situations:

  • Estrogens in oral contraceptive pills increase cortisol-binding globulin leading to an increase in total cortisol. Women who are taking oral contraceptive pills should discontinue use 6 weeks prior to the test.
  • Phenytoin, phenobarbitone, carbamazepine, rifampicin, and alcohol can induce CYP3A4 and increase hepatic clearance of dexamethasone.

Suppression is present in healthy subjects.

False-negative results can occur in subjects with Cushing syndrome in the following situations:

  • Patients with nephrotic syndrome, because of the drop in albumin and cortisol-binding globulin
  • Patients with liver failure and/or renal failure
  • Patients on drugs that inhibit CYP3A4 and decrease hepatic clearance of dexamethasone (eg, aprepitant/fos aprepitant, itraconazole, ritonavir, fluoxetine, diltiazem, cimetidine)

High-dose dexamethasone suppression test

Suppression is absent in patients with Cushing syndrome due to ectopic ACTH secretion or adrenal abnormalities. Suppression is present in patients with Cushing disease.

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Collection and Panels

Specifics for collection and panels of dexamethasone suppression tests are as follows:

Serum cortisol

See the list below:

  • Patient instruction: Preferred in the morning, no fasting needed
  • Specimen type: Blood serum
  • Collection tube: Red-top tube or gel-barrier tube
  • Unacceptable conditions: Grossly hemolyzed specimens
  • Specimen preparation: Plasma should be separated and transferred to a transport tube
  • Storage/transport temperature: Refrigerated

Panels: None

24 -hour urinary free cortisol

See the list below:

  • Patient instruction: Collection usually starts in the morning; the patient discards the first void and then collects all urine for the next 24 hours (including the first void the next morning)
  • Collection : Plastic urine containercontaining 1g of boric acid per liter
  • Specimen preparation: Urine creatinine should be measured in the same specimen to assess adequacy
  • Storage/transport temperature: Refrigerated

Panels: None

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Background

Description

Dexamethasone is a synthetic glucocorticoid that does not interact with cortisol measurement. [1, 2, 3, 4]

Low-dose dexamethasone suppression tests

In a subject with a normal hypothalamic–pituitary–adrenal (HPA) axis, a supraphysiological dose of dexamethasone can inhibit ACTH secretion by the pituitary leading to drop in cortisol level in serum, urine and saliva; such inhibition does not occur in patients with Cushing syndrome.

  • Overnight suppression test: Administer 1 mg oral dexamethasone between 11 pm and midnight. Test cortisol level between 8 am and 9 am the next morning.
  • Standard 2-day dexamethasone suppression test: Administer 0.5 mg oral dexamethasone every 6 hours for 48 hours (9 am, 3 pm, 9 pm, and 3 am). Measure cortisol level 6 hours (9 am) after the last dose. Other protocols suggest starting dexamethasone 0.5 mg orally every 6 hours starting at noon for 48 hours and checking cortisol level 2 hours (8 am) after the last dose.

The 24-hour urine free cortisol test may be used during the second day of the standard test as an end point; however, data suggest that serum cortisol has higher diagnostic accuracy and conducting both tests is not recommended. [5]

High-dose dexamethasone suppression test

In subjects with Cushing disease, a higher dose of dexamethasone (usually 8 mg) is required to suppress ACTH secretion and drop cortisol level in serum, urine, and saliva.

  • Standard 2-day dexamethasone suppression test: Serum cortisol level and/or 24-hour urinary free cortisol is measured as a baseline, and then dexamethasone 2 mg orally is taken every 6 hours for 48 hours; urine for free cortisol is collected during the test and serum cortisol is checked 6 hours after the last dose.
  • Overnight suppression test: Serum cortisol is checked at baseline, then dexamethasone (typically 8 mg) is given orally between 11 pm and midnight. Cortisol level is then checked between 8 am and 9 am the next morning.
  • Intravenous dexamethasone suppression test: Serum cortisol is checked at baseline, followed by continuous infusion of intravenous dexamethasone at a rate of 1 mg/h for 5-7 hours.

Indications/Applications

The low-dose dexamethasone suppression test is one of the screening tests for Cushing syndrome. Four highly sensitive tests are recommended by the Endocrine Society for the screening of Cushing syndrome: 24-hour urinary free cortisol, late-night salivary cortisol, overnight dexamethasone suppression test, and sta  ndard 2-day dexamethasone suppression test. [6] If Cushing syndrome is suspected, the physician should perform at least two 24-hour urinary free cortisol tests, at least 2 late-night salivary cortisol tests, or one dexamethasone suppression test. If this initial evaluation is positive, then another set of tests should be performed.

The high-dose dexamethasone suppression test is used in patients with confirmed Cushing syndrome when further workup is needed to identify the etiology. The first step is to differentiate between ACTH-dependent Cushing syndrome (ectopic ACTH and Cushing disease) and ACTH-independent Cushing syndrome (adrenal disorders). Once the Cushing syndrome is confirmed to be ACTH-dependent, a high-dose dexamethasone suppression test is performed to differentiate between Cushing disease (suppression) and ectopic ACTH.

The causes of ACTH-dependent Cushing syndrome are as follows:

The causes of ACTH-independent Cushing syndrome are as follows:

Considerations

Pseudo-Cushing syndrome can occur as a result of the following conditions:

  • Depression, anxiety disorder, obsessive compulsive disorder
  • Alcohol dependence
  • Morbid obesity
  • Poorly controlled diabetes mellitus

These conditions can overactivate the HPA axis, causing a physiological increase in circulating cortisol and leading to erroneous dexamethasone suppression test results and/or elevated 24-hour urinary free cortisol levels suggestive of Cushing syndrome.

The standard 2-day low-dose dexamethasone suppression test followed by corticotropin-releasing hormone (CRH) was designed to differentiate between Cushing syndrome and pseudo-Cushing syndrome.

The test is performed by administering 0.5 mg dexamethasone orally every 6 hours for 48 hours followed by IV CRH (1µg/kg) 2 hours after the last dose of dexamethasone; then cortisol level is measured about 15 minutes after IV CRH administration. Patients with Cushing syndrome do not suppress, whereas patients with pseudo-Cushing syndrome do suppress their cortisol level.

According to The Endocrine Society, this test can be useful in patients with equivocal 24-hour urinary free cortisol results, and a dexamethasone level should be measured at the time of CRH administration to exclude a false-positive result. [6]

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