corticotropin-releasing hormone (CRH) stimulation test

Indications

• reserved for differentiating difficult cases of Cushing's disease & ectopic ACTH-secreting tumors
• used in conjunction with high-dose dexamethasone suppression test

Reference interval

• 2-4 fold increase in mean baseline ACTH or cortisol
• ratio of IPS/peripheral blood ACTH of > 3/1

Clinical significance

• pituitary Cushing's disease
  • normal or exaggerated response to CRH
  • IPS/peripheral blood ratio of > 3/1
• ectopic ACTH-producing tumor
  • no response to CRH
  • IPS/peripheral blood ratio of < 3/1

Positive response to CRH stimulation or high dose dexamethasone suppression has 97% specificity for Cushing's disease.

A lack of response to BOTH CRH stimulation & high dose dexamethasone suppression has 100% specificity for ectopic ACTH secretion, whereas either test alone has only 64-78% negative predictive value.

ACTH concentrations peak 10-15 minutes after CRH injection. Peak values are higher in the morning than in the evening.

Serum cortisol levels peak 30-60 minutes after ACTH injection. Peak values are NOT dependent upon time of day.

Specimen

• plasma (heparin) for ACTH*
• serum or plasma for cortisol*

Procedure

• measure baseline plasma ACTH & cortisol 15 & 1 minute prior to administration of CRH
• administer 1 ug/kg of ovine CRH IV at 0900-1200 hours
• measure plasma ACTH & cortisol 5, 15, 30, 60 & 120 minutes after administration of CRH
• specimens may also be drawn from inferior petrosal sinus (IPS) at 2, 5, 10 & 15 minutes after CRH administration & compared with values obtained from peripheral blood
• procedure may be performed on an outpatient basis

* sensitivity drops & specificity increases when only cortisol response is considered

Differential diagnosis

• Cushing's disease

More general terms

• provocative clinical test

Additional terms

• adrenocorticotropic hormone; corticotropin; adrenocorticotropin (ACTH)
• corticotropin-releasing factor; corticoliberin; CRF; corticotropin-releasing hormone (CRH)
• cortisol; hydrocortisone (Cortef, Solu-Cortef, Alphaderm, Cetacort, Cortenema, Nutracort)
• Cushing's syndrome; hypercortisolism; hyperadrenocorticism; pluriglandular syndrome