Dexamethasone Suppression Screening for Cushing Disease/Syndrome


The Endocrine Society has published guidelines for screening and diagnosis of Cushing disease and Cushing syndrome.Cushing syndrome is used to describe all causes of excess glucocorticoid, while Cushing disease is reserved for the pituitary-dependent form of the disease caused by excess ACTH. When clinical signs and symptoms of excess cortisol are present, and exogenous glucocorticoid use has been excluded, screening tests are recommended by the Endocrine Society. One screening test from the following list is recommended: 24-hour urine cortisol with creatinine, collected twice on two days; late night salivary cortisol, collected twice on two days; or the 1-mg overnight or 2-mg 48-hour dexamethasone suppression test.

Dexamethasone Suppression Test

The single-dose dexamethasone test is used in screening patients suspected of having Cushing disease or Cushing syndrome. This test has not been used routinely in children and has not been well standardized in children. Consequently, its sensitivity and specificity in children has not been established. The 48-hour dexamethasone suppression test has been used in children greater than 40 kg.  In normal subjects, administration of this synthetic glucocorticoid inhibits ACTH secretion and subsequent cortisol production by negative feedback to the hypothalamus and pituitary. In patients with Cushing disease and Cushing syndrome, effective suppression of cortisol secretion does not occur with glucocorticoid administration because of continuing autonomous production of ACTH or cortisol. Dexamethasone is the preferred glucocorticoid for this test because it does not interfere with the measurement of cortisol or its urinary metabolites. Dexamethasone (1 mg for adults) is administered in the late evening, between 11 PM and midnight in order to block the early morning ACTH surge. The single-dose dexamethasone test is valuable in screening for Cushing disease and Cushing syndrome because a normal response showing sufficiently decreased cortisol levels essentially rules out either diagnosis.

Cortisol (Dexamethasone Suppression Test) With Reflex to Dexamethasone (503990)

Single-dose Overnight Dexamethasone Suppression Test Procedure (Adults):

  • Give 1 mg dexamethasone orally 11 PM to 12 MN, Draw blood 8-9 AM for plasma ACTH, and cortisol or cortisol with reflex to dexamethasone level.

48-Hour 2-mg/day Dexamethasone Suppression Test Procedure (Adults):

  • Draw 9 AM baseline cortisol on day 1 before dexamethasone administration.
  • Give dexamethasone over 48 hours in doses of 0.5 mg, beginning at 9 AM on day one, at six-hour intervals for a total of eight doses. Serum cortisol is measured six hours after the last dose of dexamethasone.
  • Draw blood for serum ACTH and cortisol at 9 AM the following morning prior to food ingestion.

Interpretation: A serum cortisol level greater than 1.7 μg/dL after the single dose or the multiple dose protocol dexamethasone is considered a positive test. This reflex profile then confirms adequate dexamethasone drug level with a dexamethasone measurement.

Limitations and Notes for All Tests

False-positive tests can be seen in patients taking estrogens, obese patients, in those who have had a poor night's sleep, and in patients under acute emotional or physical stress. Pseudo-Cushing syndrome is a term used to describe hypercortisolism, which may affect all screening tests and is due to alcohol, depression, or obesity.2 The Endocrine Society guidelines suggest referral of patients to an endocrinologist for additional testing and confirmation.

Diagnosis and Differential Diagnosis of Cushing’s Syndrome and Pseudo-Cushing’s States

In addition, patients on phenytoin, phenobarbitone, carbamazepine, and rifampicin, including those with alcohol-induced accelerated hepatic clearance of dexamethasone, have accelerated clearance of dexamethasone that may lead to a false-positive result due to the feedback of lower levels of dexamethasone to the hypothalamic-pituitary axis. Tegretol has also been shown to interfere with dexamethasone suppression. Acromegaly and Grave’s disease may also produce false-positive results for all tests. If a falsely positive result is suspected, the test should be repeated or a different test selected. For this reason, LabCorp offers dexamethasone testing as a reflex when cortisol levels are greater than 1.7 ug/dL (test number 503990).

Special Conditions: The response to dexamethasone is blunted in pregnancy due to elevated levels of transcortin, but late-night salivary cortisol and UFC are recommended as screening tests.3 Urine cortisol and salivary cortisol are understood to reflect free (unbound) cortisol and thus are not affected by elevated transcortin (CBG)levels found in pregnancy and estrogen replacement.2


1. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing's syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008 May; 93(5):1526-1540. PubMed 18334580

2. Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states. Endocr Rev. 1998 Oct; 19(5):647-672. PubMed 9793762

3. Vilar L, Freitas Mda C, Lima LH, Lyra R, Kater CE. Cushing's syndrome in pregnancy: An overview. Arq Bras Endocrinol Metabol. 2007 Nov; 51(8):1293-1302. PubMed 18209867

4. Magiakou MA, Mastorakos G, Oldfield EH, et al. Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med. 1994 Sep 8; 331(10):629-636. PubMed 8052272


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