What does a cortisol level of 6 micrograms per deciliter after a 2-day Low-Dose Dexamethasone Suppression Test (LDDST) indicate?

Interpretation of Cortisol Level After 2-Day LDDST

A cortisol level of 6 μg/dL after a 2-day Low-Dose Dexamethasone Suppression Test (LDDST) indicates normal suppression of the hypothalamic-pituitary-adrenal axis, effectively ruling out Cushing's syndrome. 1

Understanding LDDST Results

• The 2-day LDDST protocol involves administering dexamethasone 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 <1.8 μg/dL (50 nmol/L) is considered a normal response that rules out Cushing's syndrome 2, 1
• Cortisol values between 1.8-5 μg/dL represent a gray zone that may require additional testing 2
• A post-LDDST cortisol level >5 μg/dL (138 nmol/L) generally identifies patients with dysregulated cortisol secretion, particularly from adrenal incidentalomas with overt Cushing's syndrome 2

Clinical Significance of 6 μg/dL Result

• A cortisol level of 6 μg/dL after LDDST is above the standard cutoff of 1.8 μg/dL, suggesting incomplete suppression of cortisol 2, 1
• This result is consistent with one of several possible clinical scenarios:

1. Possible Cushing's Syndrome

• The value exceeds the 5 μg/dL threshold that generally identifies patients with dysregulated cortisol secretion 2
• Further diagnostic testing is warranted to confirm or exclude Cushing's syndrome 2

2. Adrenal Incidentaloma with Autonomous Cortisol Secretion

• Post-LDDST cortisol concentrations above 5 μg/dL may indicate significant hypercortisolism in patients with adrenal adenomas 3
• Higher post-LDDST cortisol concentrations correlate with larger adenomas and hormonal alterations including lower ACTH and DHEAS levels 3

3. Potential False Positive Result

• Several factors can cause falsely elevated cortisol after dexamethasone:
  • Medications affecting dexamethasone metabolism (CYP3A4 inducers like phenobarbital, carbamazepine) 2, 1
  • Rapid absorption/malabsorption of dexamethasone due to increased gut transit time 2
  • Increased corticosteroid binding globulin levels from oral estrogens or pregnancy 2

Next Steps in Evaluation

• Measure dexamethasone level along with cortisol to ensure adequate absorption and metabolism 2, 4

• Consider additional testing to confirm or exclude Cushing's syndrome:

  • Late-night salivary cortisol (LNSC) measurements (≥2 on consecutive days) 2
  • 24-hour urinary free cortisol (UFC) collections (average of 2-3 samples) 2
  • Combined dexamethasone-CRH test, which has higher diagnostic accuracy (100%) than either test alone 5

• If Cushing's syndrome is still suspected, measure ACTH to determine if it is ACTH-dependent or independent 2

• If ACTH is low, adrenal imaging (CT or MRI) is indicated to evaluate for adrenal adenoma or carcinoma 2

• If ACTH is normal or high, pituitary MRI is recommended 2

Common Pitfalls to Avoid

• Do not rely solely on a single test result to diagnose or exclude Cushing's syndrome 2, 1
• Be aware that certain medications, medical conditions, and physiological states can affect test results 2, 1
• Consider measuring dexamethasone levels simultaneously with cortisol to improve test interpretability and reduce false-positive results 2, 4
• Remember that UFC may be less reliable in patients with renal impairment or significant polyuria 2