What is the protocol for a dexamethasone (corticosteroid) suppression test?

Dexamethasone Suppression Test Protocol

The overnight 1mg dexamethasone suppression test (DST) should be performed by administering 1mg dexamethasone between 11pm and midnight, followed by measuring only serum cortisol at 8am the next morning, with a normal response being serum cortisol <1.8 μg/dL. 1

Overnight 1mg DST Protocol (First-Line Test)

• Administer 1mg dexamethasone orally between 11pm and midnight 1
• Measure serum cortisol at 8am the following morning 1
• Normal response: serum cortisol <1.8 μg/dL (50 nmol/L), which strongly predicts absence of Cushing's syndrome 1, 2
• ACTH levels should not be measured during the initial overnight DST, as this test is designed specifically to assess cortisol suppression 1

2-Day Low-Dose DST Protocol (Alternative Test)

• Administer 0.5mg dexamethasone every 6 hours (09:00,15:00,21:00,03:00) for 48 hours 3
• Measure cortisol at 0,24, and 48 hours 3
• Normal response: cortisol suppression below 50 nmol/L (1.8 μg/dL) 3
• Sensitivity: 95%, Specificity: 80% for diagnosing Cushing's syndrome 3

Interpretation of Results

• Cortisol <1.8 μg/dL: Normal response, effectively rules out Cushing's syndrome 1, 2
• Cortisol ≥1.8 μg/dL: Abnormal response, suggests possible Cushing's syndrome 1, 2
• A substantial decrease in cortisol levels demonstrates appropriate negative feedback of the HPA axis 3

Diagnostic Algorithm for Suspected Cushing's Syndrome

1. Initial screening based on clinical suspicion 2:

   • Low suspicion: Start with late-night salivary cortisol (LNSC)
   • Intermediate/high suspicion: Perform 2-3 screening tests (LNSC, 24h UFC, overnight DST)

2. If screening results are abnormal 2:

   • Repeat screening tests
   • If persistently abnormal, proceed to ACTH measurement to differentiate between ACTH-dependent and ACTH-independent causes

Potential Pitfalls and Considerations

• False positives (failure to suppress despite no Cushing's) can occur with 1, 2:

  • Rapid absorption/malabsorption of dexamethasone
  • Concomitant treatment with CYP3A4 inducers (phenobarbital, carbamazepine)
  • Increased corticosteroid binding globulin levels

• False negatives (suppression despite Cushing's) can occur with 1, 2:

  • Inhibition of dexamethasone metabolism by medications (fluoxetine, cimetidine)
  • Decreased corticosteroid binding globulin levels

• Measuring dexamethasone levels concomitantly with cortisol can reduce false-positive results, with a lower limit of normal dexamethasone concentration of 1.8 ng/mL (4.6 nmol/L) 2, 4

• The traditional 1mg overnight test may have limited sensitivity in patients with mild and/or periodic Cushing's syndrome 5, 6

Special Considerations

• DST may be preferred for shift workers and patients with disrupted circadian rhythm 2
• DST may not be reliable in women treated with oral estrogen 2
• For adrenal incidentalomas, DST is particularly useful as a first-line test, with cortisol values >5 μg/dL generally identifying patients with dysregulated cortisol secretion 2