Low Dose (1 mg) Overnight Dexamethasone Suppression Test
This should be the first line screening test for all subjects suspected of having Cushing’s syndrome.
Patients on enzyme inducing drugs eg anti-convulsants and rifampicin, may rapidly metabolise dexamethasone and give a false positive result ie no suppression. Women on oestrogen therapy may fail to suppress adequately due to increased cortisol binding globulin. If so, progress to 2 mg dexamethasone suppression test.
Patients with depression, chronic alcohol abuse, those who have serious illness or who are on dialysis are likely to give false positive results.
Principle of test
In normal subjects, dexamethasone suppresses ACTH and therefore cortisol secretion. In Cushing’s syndrome, there is incomplete suppression.
This is an outpatient test and no patient preparation is necessary.
- 1 mg dexamethasone tablet
- dose of dexamethasone for children is 0.3 mg/m2 surface area
- 1 plain blood tube
The patient takes 1 mg dexamethasone orally at 2300h and the following morning at exactly 0900h a blood sample (3 mL plain blood) is taken for plasma cortisol.
If the patient is collecting a 24 h urine sample for urinary free cortisol this should be done before taking the dexamethasone.
A normal response is shown by suppression of 0900 h cortisol to < 50 nmol/L.
Sensitivity and Specificity
The low dose test is very sensitive and if the blood sample is not taken at 9am on the day after dexamethsodne administration, the pituitary-adrenal axis may escape from suppression. This would result in a raised cortisol (a false positive test).
Suppression in patients with Cushing's syndrome is rare with this test (2%). In the reported cases the patients have been shown to metabolise dexamethasone slowly and so achieve higher circulating levels than expected. If there is strong clinical or biochemical evidence for Cushing's syndrome this test should be repeated or a formal low dose dexamethasone test is performed.
Normal subjects rarely (2%) fail to suppress with overnight dexamethasone. False positives may occur with depression (30-50%) due to the development of a reversible glucocorticoid resistance, and in patients with severe systemic illness (10-20%). Patients with renal failure on dialysis may have false positive tests due to increased clearance of dexamethasone. The effect of chronic alcohol abuse is questioned by some but there are clearly described cases (see review by Wood et al). Patients with simple obesity do not have an increased risk of false positive tests.
The formal low dose (2 day) dexamethasone suppression test may be slightly more specific.
- Crapo L. Cushing's Syndrome: a review of diagnostic tests. Metabolism 1979;28:955-979.
- Hindmarsh PC, Brook CG. Single dose dexamethasone suppression test in children: dose relationship to body size. Clin Endocrinol (Oxf) 1985;23:67-70.
- Wood P, Barth JH, Freedman DB, Perry L, Sheridan B. Evidence for the low dose dexamethasone suppression test to screen for Cushing’s syndrome - recommendations for a protocol for UK biochemistry laboratories. Ann Clin Biochem 1997;34:222-229.
JHB 14 Febuary 2013