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Background
Dexamethasone is a synthetic form of glucocorticoid. It does not interfere with the measurement of cortisol. The dexamethasone suppression test (DST) is a diagnostic test which is used to determine the adrenal gland function by know how the cortisol level in blood reacts to the dexamethasone. DST detects the hypothalamic-pituitary-adrenal (HPA) axis and diagnose the disease linked to overproduction of cortisol mainly Cushing syndrome.
Low dosage of dexamethasone suppression test (DST):
In the HPA axis, a supraphysiological dosage of dexamethasone can inhibit the secretion of ACTH by pituitary which can drop in the level of cortisol in saliva, serum and urine. Inhibition does not occur in patient who have Cushing syndrome.
Overnight suppression test: 1 mg of dexamethasone is administered orally in 11 pm to midnight and check the cortisol levels from 8 to 9 in the morning.
Standard 2 days of DST: Administer 0.5 mg dexamethasone orally for every 6 hours for 48 hours. Check the cortisol level at 6 hour (9 am) after last dosage.
Other methods which are used in the administration of dexamethasone is 0.5 mg of dosage by orally for every 6 hours in the afternoon and continue this for 48 hours. Check the cortisol level for every 2 hours after the last dose.
The 24-hour urine cortisol test is used during the 2nd day of std test at endpoint. Serum cortisol has more diagnostic accuracy and conduct both test is not suggested.
High dosage of dexamethasone suppression test (DST):
A high dosage of dexamethasone 8 mg is needed to inhibit the secretion of the ACTH and decrease the serum cortisol level in urine, serum, and saliva.
Standard 2-days of DST: 24 hours of urine-free cortisol and serum cortisol level are assessed. 2 mg of dexamethasone is given by orally in the interval of 6 hours for 48 hours. Urine is collected for the assessment of the cortisol. Serum cortisol is also checked after the 6 hours of the last dosage.
Overnight DST: Serum cortisol levels are measured at baseline, then dexamethasone (usually 8 mg) is administered orally between 11 p.m. and midnight. Cortisol levels are then measured between 8 and 9 a.m. the following morning.
Intravenous DST: The serum cortisol level is measured at the baseline which is followed by continuous infusion of the IV dexamethasone at 1 mg/hour for every 5 hours to 7 hours.
Indications/Applications
Cushing syndrome screening tests include the low-dose dexamethasone suppression test. The Endocrine Society recommends four very sensitive tests for detecting Cushing syndrome: 24-hour urine-free cortisol, late-night salivary cortisol, overnight dexamethasone suppression test, and standard 2-day dexamethasone suppression test. If Cushing syndrome is detected, doctor must do at least 2 24-hour urine-free cortisol test, 2 mid-night salivary cortisol test, and 1 DST. If the 1st evaluation is positive, more test should be undertaken.
The maximum dosage DST is performed in patients who have confirmed Cushing syndrome to know the pathogenesis.
It is necessary to differentiate the ACTH-dependent Cushing syndrome and ACTH-independent Cushing syndrome. ACTH-dependent Cushing syndrome is ectopic ACTH and ACTH-independent Cushing syndrome is adrenal disease. If the Cushing syndrome is determined whether it is dependent or independent, one can give the maximum dosage of DST.
Factors which can lead to ACTH-dependent Cushing syndrome are:
Factors which can lead to ACTH-independent Cushing syndrome:
Pseudo-Cushing syndrome can result from the following conditions:
These conditions can lead to overactivation of the HPA axis and elevates the levels of cortisol in the circulation. This can lead to abnormal results of the DST and increased level of cortisol in the 24 hours of the urine samples.
The classic 2-day reduced dosage of DST, with a corticotropin-releasing hormone, was used to differentiate between the Cushing disease and pseudo-Cushing syndrome.
The test involves delivering 0.5 mg dexamethasone orally every 6 hours for 48 hours, followed by IV CRH (1µg/kg) 2 hours after the last dosage of dexamethasone. Cortisol levels are then tested around 15 minutes following IV CRH delivery. Patients with Cushing syndrome do not lower cortisol levels, however those with pseudo-Cushing syndrome do.
As per the Endocrine Society, the DST test is used in patients who have equivocal 24 hours of urinary free cortisol test result and the dexamethasone levels must be detected at time of administration of the CRH to exclude the false-positive test result.
Reference Range
Low dose – below 50% reduction of the plasma cortisol
High dose – more than 50% reduction of plasma cortisol
Urinary free cortisol: Below 20 mcg/24 hr
Normal findings for the fast (overnight) test show that plasma cortisol levels are reduced to less than 2 mcg/dL.
Interpretation
While Cushing illness is limited to pituitary-dependent Cushing syndrome, Cushing syndrome includes all forms of glucocorticoid excess.
Dexamethasone suppression test at low doses
Cushing syndrome lacks suppression.
The following conditions may lead to false-positive result:
Estrogens by oral contraceptive pills can increase the cortisol-binding globulin which can lead to an increased levels in total cortisol. Females who are taking oral contraceptive pill must discontinue the usage before the 6 weeks of the test.
Alcohol, carbamazepine, rifampicin, phenytoin, and phenobarbitone may all activate CYP3A4 and enhance the liver’s ability to eliminate dexamethasone.
In healthy people, there is suppression.
Patients who have Cushing syndrome may have the false-negative results in the following conditions:
Patients who have liver failure, renal failure, nephrotic syndrome
Patient who is taking the medications which can inhibit the CYP3A4 and reduce the levels of dexamethasone eliminated by the liver like itraconazole, aprepitant/fos aprepitant, fluoxetine, ritonavir, cimetidine, diltiazem.
High dosage of DST:
Patients who have Cushing syndrome do not have suppression because of the abnormalities in adrenal glands or the ectopic ACTH production.
Collection And Panels
Serum cortisol sample
Sample type: Blood serum
Sample collection tube: Gel barrier tube or red top tube
Unacceptable conditions: Grossly hemolyzed samples
Sample preparation: Plasma must be separated and transfer in the transport tube
Sample storage: refrigerator
Panels: No panel
24 -hours urinary free cortisol
Sample type: Urine
Sample collection: Plastic urine container which contains 1 gm of boric acid/L
Sample preparation: Urine creatinine must be measured in the same sample to check the adequacy
Sample storage: Refrigerator
Patient instruction: Collect the samples in the morning, 1st sample is discarded and next 24 hours samples are used for the test.
Panels: No panels
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