Should an Adrenocorticotropic hormone (ACTH) level be checked at 8am along with a morning cortisol level after administering 1mg of dexamethasone at 11pm the night before to confirm Cushing's syndrome?

Diagnosing Cushing's Syndrome: The Role of ACTH in Dexamethasone Suppression Testing

No, you should not check an ACTH level at 8am with a morning cortisol after giving 1mg of dexamethasone at 11pm the night before to confirm Cushing's syndrome. 1, 2

Proper Diagnostic Approach for Cushing's Syndrome

Initial Screening Tests

• The overnight 1mg dexamethasone suppression test (DST) should be performed by administering 1mg dexamethasone between 11pm and midnight, followed by measuring only serum cortisol at 8am the next morning 1
• A normal response is serum cortisol <1.8 μg/dL (50 nmol/L), which strongly predicts the absence of Cushing's syndrome 1
• ACTH levels should not be measured during the initial overnight DST, as this test is designed specifically to assess cortisol suppression 1, 2

Interpretation of Overnight DST Results

• Cortisol values <1.8 μg/dL exclude dysregulated cortisol production 1
• Values >5 μg/dL generally identify patients with dysregulated cortisol secretion 1
• Measuring dexamethasone concomitantly with cortisol can reduce the risk of false-positive results by confirming adequate absorption 1

Diagnostic Algorithm for Cushing's Syndrome

Step 1: Confirm Hypercortisolism

• Use at least one of these first-line tests:
  • Overnight 1mg DST (measuring only cortisol) 1, 2
  • Late-night salivary cortisol (LNSC) (at least two measurements) 1
  • 24-hour urinary free cortisol (UFC) (at least 2-3 collections) 1

Step 2: Determine ACTH Dependency

• Once Cushing's syndrome is confirmed, then measure ACTH levels to differentiate between ACTH-dependent and ACTH-independent causes 1, 2
• Low ACTH indicates ACTH-independent Cushing's syndrome (adrenal source) 1, 2
• Normal or high ACTH indicates ACTH-dependent Cushing's syndrome (pituitary or ectopic source) 1, 2

Potential Pitfalls in Dexamethasone Suppression Testing

False Positive Results

• Rapid absorption/malabsorption of dexamethasone 1
• Concomitant treatment with CYP3A4 inducers (phenobarbital, carbamazepine, St. John's wort) 1
• Increased corticosteroid binding globulin levels from oral estrogens or pregnancy 1

False Negative Results

• Inhibition of dexamethasone metabolism by medications like fluoxetine, cimetidine, or diltiazem 1
• Decreased corticosteroid binding globulin levels (e.g., in nephrotic syndrome) 1

Important Clinical Considerations

• Measuring ACTH during the overnight DST is not part of standard protocol and may lead to misinterpretation 1, 2
• ACTH levels are only measured after confirming hypercortisolism to determine the source of excess cortisol production 1, 2
• For patients with disrupted day/night cycles (e.g., night-shift workers), LNSC may not be appropriate, and DST becomes more important 1
• Multiple test results should be interpreted together for increased diagnostic accuracy 1

By following this evidence-based approach, clinicians can accurately diagnose Cushing's syndrome and determine its etiology, leading to appropriate treatment decisions.