Corticotropin Releasing Factor is a 41 amino acid peptide produced in the hypothalamus. It stimulates the release of ACTH from the pituitary which in turn releases Cortisol from the adrenal gland. The Cortisol produced rapidly shuts off CRF secretion acting as a negative feedback control. CRF also releases b-Endorphin, b-Lipotropin and other related proopiomelanocortin peptides. Ectopic tumors producing ACTH also frequently produce CRF. In these patients ACTH usually does not respond to Dexamethasone suppression. CRF is markedly elevated in third trimester pregnancy. Most of it is produced by the placenta and is bound to CRF-Binding Protein and is biologically inactive. The CRF stimulation test is the most effective method of differentiating primary from secondary adrenal insufficiency and in differentiating hypothalamic from pituitary causes.