CRH Test Indication and Performance
When to Perform the CRH Test
The CRH test is indicated when you have confirmed ACTH-dependent Cushing's syndrome with an inconclusive or equivocal pituitary MRI (adenoma 6-9mm or no visible adenoma), or when you need to distinguish true Cushing's syndrome from pseudo-Cushing's states in patients with mildly elevated screening tests. 1
Without seeing your specific results, I cannot definitively say whether YOU need this test, but here are the clinical scenarios where it's required:
Primary Indications:
ACTH-dependent Cushing's with pituitary adenoma 6-9mm on MRI - This gray zone requires additional testing before proceeding to surgery or BIPSS 1
Distinguishing Cushing's disease from pseudo-Cushing's states - When screening tests (UFC, LNSC, DST) show mildly abnormal results (typically UFC within 3-fold of normal) in patients with psychiatric disorders, alcoholism, obesity, or PCOS 1
Mild Cushing's syndrome with normal or near-normal UFC - When clinical suspicion remains high despite borderline biochemical results 2, 3
How to Perform the Dexamethasone-Suppressed CRH Test (Dex-CRH Test)
The Dex-CRH test is the standard protocol, combining dexamethasone suppression with CRH stimulation to maximize diagnostic accuracy. 1, 4
Step-by-Step Protocol:
Day 1-2: Dexamethasone Suppression Phase
- Administer dexamethasone 0.5mg orally every 6 hours for 48 hours (total 8 doses = 4mg total) 4, 5
- This is the low-dose dexamethasone suppression component
Day 2: CRH Stimulation Phase
- Give the last dose of dexamethasone at 6:00 AM 4
- Two hours later (8:00 AM), measure baseline plasma dexamethasone level to confirm adequate absorption (should be >1.8 ng/mL or 4.6 nmol/L) 6
- Administer CRH (either ovine CRH 1 mcg/kg IV or human CRH 100 mcg IV) at this time 1, 7
- Draw blood samples for cortisol and ACTH at: baseline (just before CRH), then 15,30,45, and 60 minutes after CRH administration 4, 5
Interpretation Criteria:
For Cushing's Disease (Pituitary Source):
- Cortisol >38 nmol/L (>1.4 mcg/dL) at 15 minutes post-CRH indicates Cushing's disease with high sensitivity and specificity 2, 4
- Alternative cutoff: Cortisol >70 nmol/L (>2.5 mcg/dL) at 15 minutes provides 90% sensitivity and 90% specificity 5
- ACTH >27 pg/mL (>5.9 pmol/L) at 15 minutes post-CRH provides 95% sensitivity and 97% specificity for Cushing's disease 5
For Pseudo-Cushing's or Normal Physiology:
Critical Technical Points:
Measure plasma dexamethasone concentration at the time of CRH administration to confirm adequate suppression and rule out false-positive results from poor dexamethasone absorption or rapid metabolism 1, 6
The 15-minute post-CRH timepoint is most diagnostically accurate for both cortisol and ACTH measurements 5
Stop all steroidogenesis inhibitors (ketoconazole, metyrapone, osilodrostat) before testing to avoid false results 2
For cyclic Cushing's disease, confirm active hypercortisolism immediately before performing the test with LNSC, DST, or UFC 1, 2
Alternative: Standalone CRH Test
If you're not using the combined Dex-CRH protocol, a standalone CRH stimulation test can be performed:
- Administer CRH (ovine 1 mcg/kg IV or human 100 mcg IV) in the morning 7
- Measure cortisol and ACTH at baseline, 15,30,45, and 60 minutes 7
- ≥20% increase in cortisol from baseline suggests pituitary Cushing's disease 3
- This test has 88% sensitivity and 100% specificity for distinguishing Cushing's disease from ectopic ACTH syndrome 7
Important Caveats:
The Dex-CRH test shows excellent agreement with desmopressin testing when both are performed, providing confirmatory evidence 1, 2
Some ectopic ACTH-secreting tumors may respond to CRH, though typically less robustly than pituitary adenomas 2
The test may not be reliable in patients with very severe hypercortisolism or those with episodic hormonogenesis 4
If the Dex-CRH test is inconclusive or unavailable, proceed directly to bilateral inferior petrosal sinus sampling (BIPSS) for definitive localization 1