What is the protocol for performing an outpatient dexamethasone (corticosteroid) suppression test?

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Protocol for Outpatient Dexamethasone Suppression Test

The overnight 1-mg dexamethasone suppression test (DST) is the recommended protocol for outpatient screening of Cushing's syndrome, with dexamethasone administered at 11:00 PM and cortisol measured between 8:00-9:00 AM the following morning. 1

Standard Protocol for Overnight DST

  1. Preparation:

    • Ensure patient is not taking medications that interfere with dexamethasone metabolism (particularly CYP3A4 inducers)
    • Women on estrogen-containing oral contraceptives may have false positive results 2
  2. Test Administration:

    • Dose: 1 mg oral dexamethasone tablet 1, 3
    • Timing: Administer at 11:00 PM (23:00) 3
    • Alternative timing at 21:00 (9:00 PM) has been shown to be equally effective 4
  3. Sample Collection:

    • Draw blood for serum cortisol measurement between 8:00-9:00 AM the following morning 3
    • Measure dexamethasone level along with cortisol to improve test interpretability 2
  4. Result Interpretation:

    • Normal response: Cortisol suppression to <50 nmol/L (1.8 μg/dL) 5
    • Alternative cutoff: <80 nmol/L (3 μg/dL) can be used but may increase false positives 3
    • Failure to suppress suggests possible Cushing's syndrome

Special Considerations

For Obese Patients

  • False positive rates of 2.3% have been reported with the 1-mg DST in obese patients 3
  • Consider using a 2-mg overnight DST for obese patients, which has shown a lower false positive rate (2% vs 8% with 1-mg test) 5

Potential Pitfalls

  • False positives may occur due to:

    • Rapid absorption/malabsorption of dexamethasone
    • Medications affecting dexamethasone metabolism
    • Increased corticosteroid binding globulin levels
    • Pseudo-Cushing's states (psychiatric disorders, alcohol use disorder, severe obesity) 1
  • False negatives may occur due to:

    • Medications inhibiting dexamethasone metabolism
    • Cyclic Cushing's syndrome 1

Follow-up Testing

  • If DST is positive (non-suppression of cortisol), confirm with additional tests:
    • 24-hour urinary free cortisol (UFC)
    • Late-night salivary cortisol (LNSC)
    • Low-dose dexamethasone suppression test (0.5 mg every 6 hours for 2 days) 3

Alternative Protocols

  • For shift workers or patients with disrupted circadian rhythm, DST is preferred over other tests 1
  • For suspected adrenal tumor, DST is recommended as the initial test 1
  • For suspected cyclic Cushing's syndrome, LNSC may be more appropriate 1

The overnight 1-mg DST remains a reliable and convenient screening test for Cushing's syndrome in the outpatient setting, with good sensitivity and specificity when properly administered and interpreted.

References

Guideline

Cushing's Syndrome Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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