Corticotropin-releasing hormone stimulation test

Lynnette K Nieman, MD

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INTRODUCTION — It can be difficult to distinguish Cushing's disease from ectopic ACTH secretion. One test that has been used to distinguish between the two disorders is assessment of the ACTH response to the administration of corticotropin-releasing hormone (CRH) ; patients with pituitary Cushing's disease respond while those with ectopic ACTH secretion do not. The CRH stimulation test has also been used in the diagnosis of central adrenal insufficiency.
The CRH test continues to be expensive to perform; the cost of the CRH dose alone is over $300 (United States). Most investigators use an increase in either plasma ACTH or plasma cortisol concentration as the criterion for response. Multiple blood samples must be obtained (at least one basal sample and at least two and as many as eight post-CRH samples). As a result, the test should probably be performed only by specialists in carefully selected patients.
This topic will review the technique and interpretation of the CRH stimulation test, and combination tests including CRH plus arginine vasopressin, desmopressin, and low-dose dexamethasone. The vasopressin and desmopressin stimulation tests are discussed in more detail separately. 
CORTICOTROPIN-RELEASING HORMONE STIMULATION TEST — It is useful to review the procedure for performing the CRH test and the normal response before discussing its use in Cushing's syndrome and adrenal insufficiency.
Procedure — The patient usually fasts for four hours or more, after which an intravenous access line is established and synthetic ovine CRH (1 mcg [200 nmoles] per kg body weight or 100 mcg total dose) is injected as an intravenous bolus. Blood samples for ACTH and cortisol are drawn 15 (or 5) and 0 minutes before and as often as 5, 10, 15, 30, 45, 60, 90 and 120 minutes after CRH injection. However, in Cushing's syndrome, if one measures only the plasma ACTH response, the samples at -5, -0, 15 and 30 minutes are sufficient , and if one measures only the serum cortisol response, the samples at -15, 0, 45, and 60 minutes are sufficient . Normally both hormones should be measured since the criteria for a positive response may include increases in either plasma ACTH or serum cortisol concentrations .
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