Baseline Cortisol Measurement Before ACTH Stimulation Testing
Yes, a baseline cortisol level must be checked immediately before administering cosyntropin in the ACTH stimulation test. This basal measurement is essential for proper test interpretation and is explicitly required in the standard protocol 1.
Standard ACTH Stimulation Test Protocol
The test requires three cortisol measurements:
- Baseline (time 0): Draw blood for serum cortisol and ACTH before administering cosyntropin 1
- 30 minutes post-administration: Measure serum cortisol 1
- 60 minutes post-administration: Measure serum cortisol (optional but recommended) 1
The baseline cortisol provides critical diagnostic information that cannot be obtained from stimulated values alone 1.
Why the Baseline Cortisol Matters
The basal cortisol level has independent diagnostic value:
- Basal cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency without requiring stimulation testing 1
- Basal cortisol <400 nmol/L (<14.5 μg/dL) with elevated ACTH raises strong suspicion for adrenal insufficiency 1
- The increment from baseline to peak (delta cortisol) provides additional diagnostic information, with an increase >200 nmol/L (>7.2 μg/dL) supporting adequate adrenal reserve 2
Basal cortisol alone has limitations: While a very low baseline cortisol can be diagnostic, basal cortisol has only 60% sensitivity for detecting adrenal insufficiency when compared to ACTH-stimulated levels, meaning it will miss 40% of cases if used alone 3. This is why the stimulation test is necessary when baseline values are indeterminate 1.
Interpretation Requires Both Baseline and Stimulated Values
Peak cortisol response criteria:
- Peak cortisol >500-550 nmol/L (>18-20 μg/dL) at 30 or 60 minutes is normal and excludes adrenal insufficiency 1
- Peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency 1
The baseline ACTH level determines the type of adrenal insufficiency:
- High ACTH with low cortisol indicates primary adrenal insufficiency 1
- Low or inappropriately normal ACTH with low cortisol indicates secondary adrenal insufficiency 1
Critical Timing Considerations
Morning testing is strongly preferred: The test should be performed in the morning (8:00-9:00 AM) when possible, as cortisol follows a diurnal rhythm with highest levels in the morning, providing better standardization and comparison with established reference ranges 1, 4. However, morning timing is not strictly mandatory if clinical circumstances require otherwise 1.
Common Pitfalls to Avoid
Do not perform the test in patients already on corticosteroids: Exogenous steroids (including prednisone, dexamethasone, and inhaled corticosteroids like fluticasone) suppress the HPA axis and will cause false-positive results showing "adrenal insufficiency" that simply reflects expected suppression 1. Hydrocortisone must be held for 24 hours before testing, while other steroids require longer washout periods 1.
Exception for emergency situations: If dexamethasone 4 mg IV is used for suspected adrenal crisis (rather than hydrocortisone), the ACTH stimulation test can still be performed afterward because dexamethasone does not interfere with cortisol assays 1.
Never delay treatment for testing: If the patient is clinically unstable with suspected adrenal crisis, give IV hydrocortisone 100 mg immediately plus 0.9% saline infusion—do not wait for diagnostic test results, as mortality is high if untreated 1. Draw blood for cortisol and ACTH before treatment if possible, but do not delay therapy 1.