As you may remember from our steroid article, dexamethasone is a synthetic corticosteroid that is around 25x as potent than endogenous cortisol or synthetic hydrocortisone. What makes this test so useful is that dexamethasone does not directly suppress cortisol production from the adrenal cortex, it will indirectly do so by suppressing production of ACTH – more on this later.
Recall that Cushing’s syndrome refers to the overproduction of endogenous cortisol which can be either primary or secondary.
- In primary Cushing syndrome there is excessive production of cortisol by the adrenal cortex
- In secondary Cushing syndrome there is excessive production of ACTH, either by
- Pituitary (specifically referred to as Cushing’s disease)
- Ectopic foci (typically in the lung due to paraneoplastic syndrome of small cell carcinoma)
Algorithm overview
- Determine whether the patient has Cushing syndrome
- Determine whether the patient has primary or secondary Cushing syndrome (ACTH dependent or independent)
- If ACTH dependent, determine whether the patient has Cushing’s disease or ectopic foci of ACTH production
There are 2 main types of dexamethasone suppression tests:
- Low dose
- High dose
Low dose dexamethasone suppression test
Low dose dexamethasone will suppress the production of ACTH and consequently lead to a decrease in the production of cortisol in normal individuals.
In patients with Cushing’s syndrome, regardless of whether it is primary or secondary, there will be no significant decrease in cortisol levels.
Low dose dexamethasone suppression test is just one potential screening test for Cushing’s syndrome. Other tests include: elevated 24 hour urinary cortisol or elevated midnight salivary or serum cortisol (midnight when we expect cortisol to be low). Although 24 hours urinary cortisol is not as feasible in the outpatient setting, so low dose dexamethasone suppression test is usually performed instead.
- Overnight low dose suppression test
1 mg of dexamethasone is provided at 11 pm and then cortisol levels are checked at 8 am the next morning.
If cortisol levels the next morning are higher than 50 nmol/L, the patient has Cushing’s syndrome.
- 2 day low dose suppression test (“2 day-2 mg test)
Serum cortisol is measured at 8 am on the first day. Then 0.5 mg of dexamethasone is provided every 6 hours for 48 hours for a total of 4 mg (2 mg per day). Serum cortisol is checked 2 or 6 hours after last dose of dexamethasone.
If cortisol levels the next morning are higher than 50 nmol/L, the patient has Cushing’s syndrome.
Serum ACTH levels
After you have completed the low dose dexamethasone suppression test (or 24 urinary cortisol or salivary or serum midnight cortisol) and determined that the patient has Cushing’s syndrome, the next step is to find out whether it is primary or secondary which you can do by measuring the serum ACTH levels (ideally close to midnight).
- Serum ACTH <1.1 pmol/L = ACTH independent
- Serum ACTH > 4.4 pmol/L = ACTH dependent
High dose dexamethasone suppression test
High dose dexamethasone is used to distinguish between Cushing’s disease and ectopic production of ACTH – only to be used in secondary Cushing syndrome.
In patients with Cushing’s disease, where the pituitary is producing excess ACTH, high doses of dexamethasone will suppress ACTH production by a pituitary tumor. High dose dose dexamethasone will NOT suppression production ACTH by an ectopic foci.
- Overnight high dose suppression test
Serum cortisol is checked at 8 am in the morning. 8 mg of dexamethasone is provided at 11 pm and then cortisol levels are checked at 8 am the next morning.
If the cortisol levels have decreased by 50 % compared to 8 am the day before, this means that the secondary Cushing syndrome is due to a pituitary tumor.
If the cortisol levels have not decreased by 50 % then the disease is due to an ectopic foci.
CRH test
CRH test is usually recommended in addition to the high dose dexamethasone suppression test.
Measure serum cortisol and ACTH, then provide IV CRH, and then measure serum cortisol and ACTH 45 minutes afterwards.
If the patient has Cushing disease, then the CRH will stimulate the pituitary to increase ACTH and consequently cortisol.
If the patient has an ectopic foci, then the foci will not be responsive to the CRH, and ACTH and cortisol will not increase.