How do you interpret the results of a dexamethasone (corticosteroid) suppression test?

Interpreting the Dexamethasone Suppression Test

The dexamethasone suppression test (DST) is interpreted based on serum cortisol levels after dexamethasone administration, with a normal response defined as cortisol suppression to <1.8 μg/dL (50 nmol/L), which effectively rules out Cushing's syndrome. 1, 2

Types of Dexamethasone Suppression Tests

• Overnight 1-mg DST: Administered as 1 mg dexamethasone orally between 11:00 PM and midnight, with serum cortisol measured at 8:00 AM the next morning 2

  • Normal response: Serum cortisol <1.8 μg/dL (50 nmol/L)
  • Abnormal response: Serum cortisol >1.8 μg/dL (50 nmol/L)
  • Strong evidence of autonomous cortisol secretion: Serum cortisol >5.0 μg/dL (138 nmol/L) 2

• Low-Dose 2-Day DST (LDDST): Involves administering 0.5 mg dexamethasone orally every 6 hours for 48 hours, with cortisol measurement at 0,24, and 48 hours 2

  • Normal response: Suppression to <1.8 μg/dL (50 nmol/L) 2
  • Sensitivity of 95% and specificity of 80% for diagnosing Cushing's syndrome 1

• High-Dose DST: Used for differential diagnosis of ACTH-dependent Cushing's syndrome 3, 4

  • Helps distinguish between pituitary and ectopic sources of ACTH 4

Improving Test Accuracy

• Measure dexamethasone levels concomitantly with cortisol to reduce false-positive results 1, 2, 5

  • Lower limit of normal dexamethasone concentration: 1.8 ng/mL (4.6 nmol/L) 1
  • Approximately 6% of patients may not achieve adequate dexamethasone levels, accounting for 40% of false positive results 5

• Consider timing of measurements as this can affect interpretation 3

  • Multiple sampling times may improve diagnostic accuracy 3

Potential Pitfalls and False Results

False Positives (Failure to Suppress)

• Rapid dexamethasone absorption or malabsorption 1, 2
• Medications that induce CYP3A4 (phenobarbital, carbamazepine, phenytoin, rifampin) 2, 6
• Increased cortisol-binding globulin levels (pregnancy, estrogen therapy) 1, 2
• Pseudo-Cushing's states (depression, alcoholism, obesity) 7, 1
• Indomethacin use can cause false negative DST results 6

False Negatives (Inappropriate Suppression)

• Medications that inhibit dexamethasone metabolism (fluoxetine, cimetidine, diltiazem) 1, 2
• Decreased cortisol-binding globulin levels 1
• Mild cases of Cushing's syndrome may show partial suppression 8, 9
  • Up to 18% of patients with Cushing's disease can suppress serum cortisol to <5 μg/dL 8
  • 8% may suppress to <2 μg/dL 8

Special Considerations

• Adrenal incidentalomas: DST is particularly useful as a first-line test, with cortisol values >5 μg/dL generally identifying patients with dysregulated cortisol secretion 1

• Shift workers and disrupted circadian rhythm: DST may be preferred over other tests like urinary free cortisol or late-night salivary cortisol 1

• Women on oral estrogen: DST may not be reliable; consider alternative tests 1

• Suspected pseudo-Cushing's states: The combined low-dose dexamethasone-CRH test (Dex-CRH) may help distinguish between ACTH-dependent Cushing's syndrome and pseudo-Cushing's states 7, 1

Diagnostic Algorithm

1. Initial screening based on clinical suspicion 7:

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

2. Interpret results 7:

   • Normal screening results: Cushing's syndrome is unlikely
   • Abnormal results: Repeat screening tests
   • Persistently abnormal results: Proceed to ACTH measurement

3. Based on ACTH levels 7:

   • Low ACTH: ACTH-independent Cushing's syndrome (adrenal imaging)
   • Normal/high ACTH: ACTH-dependent Cushing's syndrome (pituitary MRI)

4. For ACTH-dependent cases 7, 4:

   • Pituitary adenoma ≥10 mm: Presumed Cushing's disease
   • Pituitary adenoma <6 mm or no adenoma: Perform inferior petrosal sinus sampling (IPSS)
   • Pituitary adenoma 6-9 mm: Consider CRH and DDAVP testing or IPSS

Important Caveats

• The traditional cutoff of 5 μg/dL may miss cases of Cushing's syndrome; the more stringent cutoff of <1.8 μg/dL is now recommended 9, 2

• Combined testing approaches (e.g., DST plus CRH test) provide higher sensitivity and specificity than either test alone 4

• Measuring dexamethasone levels can significantly improve test specificity by identifying cases where inadequate dexamethasone levels led to false positive results 5

• The low-dose DST can sometimes provide information for differential diagnosis between pituitary and ectopic ACTH sources, not just for screening 4