Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide that is the major physiologic ACTH secretagogue . There is considerable sequence homology of CRH among species, particularly in the amino-terminal region, which is required for biologic activity. As a result, both ovine and human sequences are used in endocrine testing to:
- Evaluate the cause of ACTH-dependent Cushing's syndrome (with or without vasopressin analogs).
- Discriminate between pseudo-Cushing's and Cushing's syndrome.
- Discriminate between pituitary or hypothalamic localization of central adrenal insufficiency.
- To assess ACTH suppression in patients suspected of primary adrenal mild Cushing's syndrome when basal ACTH levels are incompletely suppressed between 5 and 15 pg/mL [1.1 to 3.3 pmol/L]. (See "Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia".)
The CRH test is expensive; the cost for 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. In the United States, ovine CRH is available and carries FDA labeling for the differential diagnosis of Cushing's syndrome. In Europe, the human analog is available.
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. (See "Vasopressin and desmopressin stimulation test".)
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.