Dexamethasone Suppression Test vs. ACTH Stimulation Test: These Are Completely Different Tests
No, the dexamethasone suppression test and ACTH stimulation test are fundamentally different diagnostic procedures that serve opposite purposes and should never be confused. The dexamethasone suppression test evaluates for cortisol excess (Cushing syndrome), while the ACTH stimulation test evaluates for cortisol deficiency (adrenal insufficiency) 1.
Key Distinctions Between the Tests
Dexamethasone Suppression Test (DST)
- Purpose: Screens for autonomous cortisol overproduction and Cushing syndrome 2, 3
- Mechanism: Administers dexamethasone (typically 1 mg overnight) to suppress normal cortisol production; failure to suppress indicates autonomous cortisol secretion 2, 4
- Interpretation: Cortisol levels >138 nmol/L (5 μg/dL) after dexamethasone indicate likely autonomous cortisol production 4, 5
- Clinical context: Used when suspecting cortisol excess, particularly relevant in your 53-year-old patient with suspected lung cancer, as 30-50% of small cell lung cancer patients have biochemical evidence of ectopic ACTH production 3
ACTH Stimulation Test
- Purpose: Evaluates adrenal reserve and diagnoses adrenal insufficiency 1
- Mechanism: Administers synthetic ACTH to stimulate cortisol production; inadequate cortisol response indicates adrenal insufficiency 1
- Interpretation: Used when baseline cortisol and ACTH results are indeterminate 1
- Clinical context: Confirms suspected adrenal insufficiency when morning cortisol and ACTH levels are equivocal 1
Critical Clinical Pitfall in Your Patient Population
In patients with suspected lung cancer and potential ectopic ACTH syndrome, you must diagnose hypercortisolism during initial evaluation before starting chemotherapy, as untreated hypercortisolism increases mortality from opportunistic infections and venous thromboembolism 2, 3. Order serum potassium, bicarbonate, glucose, and sodium alongside cortisol and ACTH, as hypokalemia, metabolic alkalosis, and hyperglycemia characterize ectopic ACTH syndrome 2, 6.
Important Interaction Between These Tests
If you need to perform emergent therapy for suspected adrenal insufficiency while the diagnosis remains unclear, use dexamethasone 4 mg IV rather than hydrocortisone, because dexamethasone does not interfere with subsequent ACTH stimulation testing 1. This allows you to treat presumed adrenal crisis while preserving the ability to confirm the diagnosis.
Drug Interactions Affecting DST Accuracy
Phenytoin, phenobarbital, ephedrine, and rifampin enhance dexamethasone metabolism, potentially causing false-negative DST results and requiring cautious interpretation 7. Indomethacin also causes false-negative DST results 7.
Post-Treatment Monitoring Consideration
After initiating cancer treatment in ectopic ACTH syndrome, patients may paradoxically develop acute adrenal insufficiency due to rapid tumor response, requiring close monitoring and potential transition from evaluating cortisol excess to managing cortisol deficiency 2.