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High Dose Dexamethasone Suppression Test


Patients with definite Cushing's syndrome of unknown aetiology.


Patients on enzyme inducing drugs e.g. anti-convulsants may rapidly metabolise dexamethasone.
Oestrogens (e.g. pregnancy, HRT or COC) may induce cortisol binding protein and artefactually increase total cortisol levels.
Care in patients with severe depression or hypomania.


Stop all oral oestrogen therapy 6 weeks prior to test. Again implants can cause problems.
This is an inpatient test and should only be performed after at least 2 baseline values for 24 hour urinary free cortisol and 0900h cortisol and ACTH levels (see below).


  1. This test often follows the LDDST. The final sample from the LDDST (2+48) can often be used as the basal sample for this test. Basal 0900h cortisol (red top Vacutainer) and ACTH (purple tops Vacutainers on ice) are measured ("8+0").
  2. During the test the patient takes 2 mg dexamethasone p.o. at strict 6 hour intervals (i.e. 0900h, 1500h, 2100h and 0300h) for 48 hours.
  3. The cortisol and ACTH are measured at 0900h on the first day of the test and 48 hours later ("8+48"). In some patients the dexamethasone may be continued for 72 hours in which case an additional 0900h serum cortisol and ACTH are taken ("8+72").


If the 0900h cortisol is less than 50% of the basal value after 48 hours of dexamethasone this is classified as showing suppression. Suppression with high dose dexamethasone is usually seen in Cushing's disease but not in ectopic ACTH production or adrenal tumours.


The high dose dexamethasone test is useful but not totally reliable in the differential diagnosis of Cushing's syndrome as it is neither very sensitive nor specific. Suppression occurs in 75% of patients with Cushing's disease, 10-25% of patients with ectopic ACTH and 0-6% of patients with adrenal tumours. Patients with ectopic ACTH who show suppression tend to have occult and relatively benign tumours with lower levels of ACTH and cortisol. These patients are very hard to differentiate from Cushing's disease.
The 0900h cortisol after 48 hours is considered to be the best parameter to use to discriminate between Cushing's disease and ectopic ACTH. The criterion of 50% suppression at 48 hours should not be applied too rigidly as many cases of Cushing's disease will suppress by 40 or 45% or suppress after 72 hours. In difficult cases it is advisable to repeat the test as no patients with an adrenal tumour have been shown to have reproducible suppression and cases of Cushing's syndrome may show cyclical variation.


Crappo A., Metabolism 28, 955-979 (1979).