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Dexamethasone Suppression Test 

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

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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Contributor Information and Disclosures
Author

Georges Elhomsy, MD Fellow in Endocrinology, St Louis University School of Medicine

Georges Elhomsy, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

References
  1. Pesonen AK, Martikainen S, Kajantie E, Heinonen K, Wehkalampi K, Lahti J, et al. The associations between adolescent sleep, diurnal cortisol patterns and cortisol reactivity to dexamethasone suppression test. Psychoneuroendocrinology. 2014 Jul 18. 49C:150-160. [Medline].

  2. Sorenson AN, Sullivan EC, Mendoza SP, Capitanio JP, Higley JD. Serotonin transporter genotype modulates HPA axis output during stress: effect of stress, dexamethasone test and ACTH challenge. Transl Dev Psychiatry. 2013 Sep 9. 1:21130. [Medline]. [Full Text].

  3. Zografos GN, Perysinakis I, Vassilatou E. Subclinical Cushing's syndrome: Current concepts and trends. Hormones (Athens). 2014 Jul. 13(3):323-337. [Medline].

  4. Savic D, Knezevic G, Damjanovic S, Antic J, Matic G. GR gene BclI polymorphysm changes the path, but not the level, of dexamethasone-induced cortisol suppression. J Affect Disord. 2014 Oct 15. 168:1-4. [Medline].

  5. The Adrenal Cortex. Stewart PM, Krone NP. Melmed: Williams Textbook of Endocrinology, 12th ed. Philadelphia, PA Saunders Company; 2011:chap 15.

  6. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008 May. 93(5):1526-40. [Medline].

 
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