What does a decrease in cortisol level from 19 to 6 in response to the 2-day Low-Dose Dexamethasone Suppression Test (LDDST) indicate for a patient suspected of having Cushing's syndrome?

Interpretation of 2-Day LDDST Results: Cortisol Decrease from 19 to 6

A cortisol decrease from 19 to 6 during a 2-day Low-Dose Dexamethasone Suppression Test (LDDST) indicates appropriate suppression of the hypothalamic-pituitary-adrenal axis, effectively ruling out Cushing's syndrome. 1

Understanding LDDST Results

• The LDDST is a key diagnostic test for confirming Cushing's syndrome, with cortisol suppression below 50 nmol/L (1.8 μg/dL) considered normal 1
• In the 2-day LDDST protocol, dexamethasone is administered at 0.5 mg every 6 hours (09:00,15:00,21:00,03:00) for 48 hours, with cortisol measurements at 0,24, and 48 hours 1
• A post-LDDST cortisol level ≥50 nmol/L (≥1.8 μg/dL) is considered diagnostic for Cushing's syndrome with 95% sensitivity and 80% specificity 1
• Your cortisol decrease from 19 to 6 represents significant suppression, indicating normal HPA axis function 1

Clinical Significance

• Proper cortisol suppression during LDDST effectively rules out autonomous cortisol production seen in Cushing's syndrome 2
• The substantial decrease in cortisol levels (from 19 to 6) demonstrates appropriate negative feedback of the HPA axis in response to exogenous glucocorticoids 1
• This result is inconsistent with the pattern seen in Cushing's syndrome, where cortisol would remain elevated (≥50 nmol/L) despite dexamethasone administration 1
• Research shows that higher post-LDDST cortisol concentrations correlate with larger adrenal adenomas and greater autonomous glucocorticoid secretion 2

Diagnostic Algorithm for Suspected Cushing's Syndrome

1. Initial screening tests (if clinical suspicion exists):

   • 24-hour urinary free cortisol (UFC) measurements (3 collections) 1, 3
   • Late-night salivary cortisol 3
   • Overnight 1-mg dexamethasone suppression test 1
   • 2-day LDDST (as in your case) 1

2. Interpretation of LDDST results:

   • Suppression to <50 nmol/L (<1.8 μg/dL): Normal response (rules out Cushing's) 1
   • Failure to suppress to <50 nmol/L: Suggests Cushing's syndrome 1

3. If Cushing's syndrome is confirmed, determine ACTH dependency:

   • Measure morning plasma ACTH 1
   • Perform CRH stimulation test 1, 4
   • Consider combined dexamethasone-CRH test for borderline cases 5, 4

Potential Pitfalls and Considerations

• False positive results (failure to suppress despite no Cushing's) can occur with:

  • Medications affecting dexamethasone metabolism (CYP3A4 inducers like phenobarbital, carbamazepine) 1
  • Increased cortisol-binding globulin from oral estrogens or pregnancy 1
  • Stress, severe illness, or depression (pseudo-Cushing's states) 1, 4

• False negative results (suppression despite Cushing's) can occur with:

  • Medications inhibiting dexamethasone metabolism (fluoxetine, cimetidine) 1
  • Cyclic Cushing's syndrome (if tested during a normal cortisol production phase) 1
  • Decreased cortisol-binding globulin (nephrotic syndrome) 1

• For indeterminate cases, consider:

  • Repeating the test 5
  • Combined dexamethasone-CRH test (higher diagnostic accuracy) 4
  • Very high-dose dexamethasone test (32 mg) for resistant cases 6