Dexamethasone Suppression Test

Introduction

The dexamethasone suppression test (DST) is a screening test to rule out Cushing syndrome.

  • Dexamethasone suppression test is used in combination with other tests (midnight plasma cortisol, late-night salivary cortisol, and/or 24-hour urinary free cortisol) to confirm the diagnosis.

A suppression test, in general, involves giving the patient a substance that would normally cause the inhibition of the release of the hormone.

  • However, due to the excessive amounts of hormone or hyperfunction of the endocrine organ, a patient with the disease state would fail to have the hormone levels suppressed.



Regimen

It may be administered as a

  • Low-dose test
    • Screening for Cushing syndrome
    • Overnight test: 1 mg PO between 11 PM and 12 AM; cortisol level tested between 8 AM and 9 AM on following morning.
    • Standard 2-day test: 0.5 mg PO q6hr (9 AM, 3 PM, 9 PM, 3 AM) for 2 days; cortisol level tested 6 hours after final dose (9 AM).
  • High-dose test
    • Confirmed Cushing syndrome in which further workup is needed to identify whether hormone excess is the result of Cushing syndrome or other causes.
    • Standard 2-day test: After determination of baseline serum cortisol or 24-hr urinary free cortisol, 2 mg PO q6hr for 2 days; urine for free cortisol is collected during test, and serum cortisol is checked 6 hours after final dose.
    • Overnight test: After determination of baseline serum cortisol, 8 mg (typically) PO between 11:00 PM and midnight; cortisol level tested between 8:00 and 9:00 AM on following morning.
    • IV test: After determination of baseline serum cortisol, 1 mg/hr by continuous IV infusion for 5-7 hours.



Interpretation with Low-dose Test

While a fasting plasma cortisol level greater than 5 mcg/dL is consistent with Cushing’s syndrome, lower levels (>1.8 mcg/dL) may not fully rule out Cushing’s syndrome, as some patients may be able to slightly suppress cortisol.

  • This lower level may increase the sensitivity but at the expense of the specificity.

NOTE: There are many exceptions, and the test must be interpreted with caution.



Factors Affecting Test Results

Ideally, all medications should be discontinued for 24 to 48 hours prior to the test.

  • Drugs that increase the metabolism of dexamethasone by induction of cytochrome P450(CYP) 3A4 may increase the possibility of a false positive.
    • Examples include phenobarbital, phenytoin, carbamazepine, primidone, rifampin, rifapentine, ethosuximide.
  • Estrogen stimulates cortisol binding globulin, causing increased total cortisol concentration.
    • Examples include oral contraceptive pill, menopausal hormone therapy.
  • Drugs that decrease the metabolism of dexamethasone by inhibition of CYP 3A4 may increase the possibility of a false negative.
    • Examples include: aprepitant/fosaprepitant, itraconazole, ritonavir, fluoxetine, diltiazem, cimetidine.

Conditions that may reduce the clearance of dexamethasone and increase the possibility of a false negative include liver and renal failure.

Cortisol levels may be physiologically increased during hypoglycemia, stress, and pregnancy, making interpretation of cortisol excess difficult.



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