What does a high dose dexamethasone (corticosteroid) suppression test with suppression indicate?

High Dose Dexamethasone Suppression Test Interpretation

Suppression of cortisol in a high-dose dexamethasone suppression test indicates Cushing's disease (pituitary adenoma) as the source of hypercortisolism. 1, 2

Mechanism and Interpretation

The high-dose dexamethasone suppression test works by exploiting the different feedback mechanisms in various forms of Cushing's syndrome:

• Positive result (suppression occurs):

  • Indicates pituitary-dependent Cushing's disease (ACTH-secreting pituitary adenoma)
  • These tumors retain some sensitivity to negative feedback from high-dose dexamethasone
  • Typically shows >50% suppression of cortisol levels from baseline

• Negative result (no suppression):

  • Suggests either ectopic ACTH syndrome or adrenal tumor
  • These sources are autonomous and resistant to dexamethasone feedback

Diagnostic Criteria

According to the Endocrine Society guidelines, the following criteria are used to interpret results 1:

• Standard criteria: >50% suppression of cortisol indicates pituitary source
• More stringent criteria: >80% suppression has a likelihood ratio of 10.1 for pituitary disease
• Highest specificity: >90% suppression has "infinite" likelihood ratio (100% specificity) for pituitary disease 3

Test Performance Characteristics

• In some studies, up to 42% of patients with confirmed Cushing's disease failed to show suppression after the standard 8 mg dexamethasone test 2
• Using urinary free cortisol (UFC) as an endpoint may improve diagnostic accuracy:
  • UFC suppression >90% is associated with 100% specificity for pituitary disease 3
  • Combined measurement of UFC and 17-hydroxysteroid excretion improves diagnostic performance to 86% accuracy 3

Important Considerations

• False positive results (suppression in non-pituitary disease) are rare but can occur in some cases of macronodular adrenal hyperplasia 2
• Medications that affect dexamethasone metabolism (particularly CYP3A4 inducers) can interfere with test results 1
• Women on estrogen-containing oral contraceptives may have altered dexamethasone metabolism 1
• Very high dose testing (32 mg) may be useful in patients who don't suppress with standard high-dose testing 2

Clinical Algorithm

1. Establish the diagnosis of Cushing's syndrome using screening tests (1-mg overnight DST, late-night salivary cortisol, or 24-hour UFC)
2. Measure plasma ACTH to determine if Cushing's syndrome is ACTH-dependent or independent
3. If ACTH-dependent, perform high-dose dexamethasone suppression test
4. Interpret results:

   • 50% suppression: Likely pituitary source

   • 90% suppression: Definitive for pituitary source

   • <50% suppression: Consider ectopic ACTH or need for very high-dose testing
5. Confirm with imaging (pituitary MRI) and potentially inferior petrosal sinus sampling in equivocal cases

The high-dose dexamethasone suppression test remains a valuable tool in the differential diagnosis of Cushing's syndrome, particularly when used in conjunction with other diagnostic modalities.