Does the Adrenocorticotropic Hormone (ACTH) test require dexamethasone?

Does the ACTH Test Require Dexamethasone?

No, the ACTH test does not require dexamethasone—ACTH levels should be measured independently to determine if Cushing's syndrome is ACTH-dependent or ACTH-independent. 1, 2

Understanding the Distinction Between Tests

The confusion likely arises from conflating two separate diagnostic procedures:

• ACTH measurement: A simple blood test drawn in the morning (8:00-9:00 AM) to measure plasma ACTH levels 2, 3
• Dexamethasone suppression test (DST): A functional test that measures cortisol suppression after dexamethasone administration 1, 4

These are distinct tests with different purposes and should not be combined for initial ACTH measurement. 4

Proper Diagnostic Algorithm

Initial Screening for Cushing's Syndrome

When Cushing's syndrome is suspected, start with one or more of these screening tests 1:

• Late-night salivary cortisol (LNSC): At least 2-3 tests 1
• 24-hour urinary free cortisol (UFC): 2-3 collections 1
• Overnight 1 mg dexamethasone suppression test: Give 1 mg dexamethasone at 11 PM-midnight, measure only cortisol (not ACTH) at 8 AM the next morning 4

Measuring ACTH After Confirming Hypercortisolism

Once Cushing's syndrome is confirmed, measure morning (8:00-9:00 AM) plasma ACTH without any dexamethasone preparation 2, 3:

• ACTH >5 pg/mL: Indicates ACTH-dependent Cushing's syndrome 2, 3
• ACTH <5 pg/mL or undetectable: Indicates ACTH-independent (adrenal) Cushing's syndrome 2, 3
• ACTH >29 pg/mL: Has 70% sensitivity and 100% specificity for Cushing's disease 2, 3

Critical Pitfall to Avoid

Do not measure ACTH during the overnight dexamethasone suppression test. 4 This is not part of standard protocol and leads to misinterpretation because:

• Dexamethasone blocks the normal circadian rhythm of ACTH without significantly decreasing ACTH levels 5
• Only basal, biologically inactive ACTH is secreted in the morning after dexamethasone, which cannot be further suppressed 5
• The DST is designed specifically to assess cortisol suppression, not ACTH levels 4

Special Circumstances Where Dexamethasone May Be Used

There are specific advanced tests where dexamethasone and ACTH measurement are combined, but these are not the standard ACTH test 1:

• Dex-CRH test: Used to distinguish true Cushing's syndrome from pseudo-Cushing's states 1
• High-dose dexamethasone suppression test: Used to differentiate Cushing's disease from ectopic ACTH syndrome, though this has poor diagnostic utility 6

ACTH Stimulation Test (Different Test Entirely)

If you're asking about the ACTH stimulation test (used to diagnose adrenal insufficiency, not Cushing's syndrome), dexamethasone pretreatment is generally not required 7:

• Standard ACTH stimulation testing does not require dexamethasone preparation 7
• If the test cannot be performed immediately in critically ill patients, dexamethasone (not hydrocortisone) can be given because it doesn't interfere with cortisol measurement 8
• Dexamethasone pretreatment offers no practical advantage and complicates interpretation 7

Bottom Line

For diagnosing Cushing's syndrome, measure morning ACTH levels directly without dexamethasone. 2, 3, 4 Dexamethasone suppression testing and ACTH measurement are separate diagnostic tools that serve different purposes in the evaluation algorithm. 1, 4