What does the Corticotropin-Releasing Hormone (CRH) stimulation test show if a Dexamethasone (Dex) suppression test shows Adrenocorticotropic Hormone (ACTH) suppression with a cortisol level of 2.2 and a Dex level of 402?

Interpretation of CRH Stimulation Test Following Dexamethasone Suppression

With adequate dexamethasone suppression (cortisol 2.2 μg/dL, ACTH 11 pg/mL, dex level 402 ng/mL), a CRH stimulation test showing a cortisol rise >38 nmol/L (1.4 μg/dL) at 15 minutes would indicate ACTH-dependent Cushing's disease rather than normal physiology or pseudo-Cushing's states. 1, 2

Understanding Your Current Results

Your dexamethasone suppression test demonstrates:

• Adequate dexamethasone absorption and compliance - A dex level of 402 ng/mL confirms proper medication intake and metabolism, eliminating false-positive concerns from inadequate dexamethasone levels 1
• Appropriate cortisol suppression - Cortisol of 2.2 μg/dL (61 nmol/L) is below the typical cutoff of <1.8 μg/dL (50 nmol/L) for normal suppression 3, 4
• Suppressed but detectable ACTH - ACTH of 11 pg/mL is suppressed but not undetectable, which is expected with adequate dexamethasone suppression 5

What the CRH Test Will Show

The Dex-CRH test operates on a critical principle: only patients with true ACTH-dependent Cushing's disease will demonstrate a cortisol response to CRH after adequate dexamethasone suppression 1

In Normal Individuals:

• Plasma cortisol remains <38 nmol/L (1.4 μg/dL) for at least 30 minutes after CRH administration 2
• This occurs because normal corticotrophs remain suppressed by dexamethasone and do not respond to CRH stimulation 2

In Cushing's Disease:

• 15-minute post-CRH cortisol exceeds 38 nmol/L (1.4 μg/dL) in 100% of patients with surgically-proven mild Cushing's disease 2
• ACTH-secreting pituitary adenomas demonstrate paradoxical responsiveness to CRH despite dexamethasone suppression 6
• This reflects the autonomous nature of the adenoma and its resistance to normal negative feedback mechanisms 6

In Pseudo-Cushing's States:

• Patients with physiologic hypercortisolism (depression, alcoholism, obesity) show blunted ACTH responses to CRH similar to normal individuals 1
• The chronic hypercortisolism in pseudo-Cushing's maintains negative feedback, preventing CRH responsiveness 1

Diagnostic Performance

The Dex-CRH test demonstrates:

• 100% sensitivity and specificity for differentiating mild Cushing's disease from normal physiology when using the 38 nmol/L cortisol cutoff at 15 minutes 2
• Excellent agreement with desmopressin testing when both are performed, providing confirmatory evidence 1
• Superior diagnostic accuracy compared to standard high-dose dexamethasone suppression testing alone 7, 8

Clinical Context and Interpretation

Given your baseline results showing adequate suppression:

• If CRH stimulation produces cortisol >38 nmol/L at 15 minutes: This confirms ACTH-dependent Cushing's disease, and you should proceed with pituitary MRI imaging 3, 5
• If cortisol remains <38 nmol/L throughout the test: This indicates normal HPA axis function or successfully treated/resolved hypercortisolism 2

Important Caveats

• Cyclic Cushing's disease may produce false-negative results if testing occurs during a quiescent phase - hypercortisolemia must be confirmed immediately prior to the test 3
• Ectopic ACTH-secreting tumors typically show less robust responses to CRH compared to pituitary adenomas, though some may respond 1, 7
• The test assumes you are not taking medications that interfere with dexamethasone metabolism (CYP3A4 inducers or inhibitors), though your adequate dex level suggests this is not an issue 1

Next Steps Based on Results

If CRH-stimulated cortisol is elevated:

• Obtain high-quality pituitary MRI with thin slices (3T preferred) to identify adenoma 3
• If adenoma ≥10 mm is found, presume Cushing's disease 3
• If no adenoma or <6 mm lesion, proceed to bilateral inferior petrosal sinus sampling (BIPSS) with central-to-peripheral ACTH ratio criteria of ≥2:1 baseline and ≥3:1 post-stimulation 3, 5

If CRH-stimulated cortisol remains suppressed:

• Consider alternative diagnoses for presenting symptoms 2
• Evaluate for pseudo-Cushing's states if clinical suspicion remains 1