Dexamethasone Suppression Test

• Dexamethasone is a synthetic steroid with 25 times the glucocorticoid activity of cortisol. It does not interfere with cortisol measurement.
• Dexamethasone leads to suppression of adrenal cortisol secretion in normal individuals. In patients with Cushing’s syndrome there is incomplete suppression.
• 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.

Indication

• As a screening test to exclude Cushing’s syndrome

Contraindication/SideEffect

• None

Precaution

• This procedure may be contraindicated in patients with active peptic ulcer disease

Overnight Screening Test

1 DAY PROTOCOL
Briefing	·         briefed on when to take the dexamethasone and to return the following morning for a blood test at 9am. ·         If the patient is collecting a 24hr urine sample for urinary free cortisol, this should be completed before taking the dexamethasone
DAY 1: 11.00PM-12.00Midnight	·         Take 1 mg Dexamethasone	·         2 X 0.5mg Tab
DAY2: 8.00AM-9.00AM	·         Take blood sample	·         plain, red top vacutainer tube

Interpretation

< 50 nmol/L (1.8 mcg/Dl)	·         Normal suppresion ·         Normal suppression makes a diagnosis of Cushing’s Syndrome unlikely. ·         The specificity of the test is 87%.
> 50 nmol/L (1.8 mcg/dL)	·         Failure of suppression does not confirm Cushing’s Syndrome. ·         Abnormal results with this test should be followed by further investigation under the supervision of an endocrinologist (eg. urine free cortisol, diurnal rhythm studies, low and high dose dexamethasone suppression test, ACTH measurements)
failure of cortisol suppression can also occur in	·         Severe endogenous depression - these patients may have abnormal circadian rhythm. ·         Alcoholism (pseudo-Cushing’s syndrome) ·         Severe stressful illness/infection - the test should not be performed in this situation. ·         Hepatic enzyme-inducing drugs - (phenytoin, phenobarbitone, rifampicin, etc). These may cause more rapid metabolism of dexamethasone, such that normal suppression of the pituitary-adrenal axis fails ·         Oestrogen therapy - induces high levels of cortisol binding globulin, such that the test is not interpretable. ·         Failure to take dexamethasone correctly - check with patient. ·         Glucocorticoid resistance syndrome - rare, familial disorder and patients are not Cushingoid. ·         Obesity ·         Renal failure

Two-Day Low Dose Test

2 DAY PROTOCOL
DAY 1: 8AM,2PM,8PM,2AM	Take 0.5 mg Dexamethasone  6 hourly	0.5mg Tab
DAY2: 8AM,2PM,8PM,2AM	Take 0.5 mg Dexamethasone  6 hourly	0.5mg Tab
	24-H urine free cortisol 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)	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
DAY 3: 8AM	Take blood sample	plain, red top vacutainer tube Other protocols suggest starting checking cortisol level 2 hours (8 am) after the last dose

High Dose Dexamethasone suppression tests

• The basis for the high-dose suppression tests is the fact that ACTH secretion in Cushing's disease is only relatively resistant to glucocorticoid negative feedback inhibition and will not suppress normally with either the overnight 1 mg or the two-day, low-dose test

1 DAY PROTOCOL
DAY 1: 11.00PM-12.00Midnight	·         Take 8 mg Dexamethasone	·
DAY2: 8.00AM-9.00AM	·         Take blood sample	·         plain, red top vacutainer tube
Interpretation	·         Undetectable	·         Normal
	·         <5 mcg/dL (140 nmol/L)	·         Cushing's disease
2 DAY PROTOCOL
DAY 1: 8AM,2PM,8PM,2AM	·         Take 2 mg Dexamethasone  6 hourly	·
DAY2: 8AM,2PM,8PM,2AM	·         Take 2 mg Dexamethasone  6 hourly	·
	·         24-H urine free cortisol	·
DAY 3: 8AM	·         Take blood sample	·         plain, red top vacutainer tube
Investigation	·         Urinary free cortisol excretion is less than 5 mcg (14 nmol) per 24 hours	·         Normal

Recommendation:

• 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 standard 2-day dexamethasone suppression test
• 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

References:

1. http://emedicine.medscape.com/article/2114191-overview#showall
2. http://www.pathology.leedsth.nhs.uk/dnn_bilm/Investigationprotocols/Pituitaryprotocols/1mgDexamethasoneOvernightSuppressionTest.aspx
3. www.uptodate.com
4. Low Dose Overnight Dexamethasone Suppression Test for the First Line Investigation of Cushing’s Syndrome. Pathology at the Royal Derby Hospital