Corticorelin (Acthrel)

Prescription

Corticorelin is a synthetic version of corticotropin-releasing hormone (CRH), the 41-amino-acid hypothalamic peptide that sits at the very top of the body's stress-hormone axis. In normal physiology, the hypothalamus releases CRH, which travels to the pituitary and stimulates it to secrete ACTH, which in turn drives the adrenal glands to make cortisol. Corticorelin lets clinicians test this pathway deliberately. The FDA-approved product, Acthrel, is corticorelin ovine triflutate — the ovine (sheep) sequence, which is slightly longer-acting in humans than the human sequence and gives a robust, sustained ACTH response. The main diagnostic use is in evaluating Cushing's syndrome — a state of excess cortisol. Once excess cortisol is confirmed, the key question is where it comes from: a pituitary tumor over-producing ACTH (Cushing's disease), an ectopic ACTH-secreting tumor elsewhere in the body, or an adrenal source. In the CRH stimulation test, corticorelin is injected and ACTH and cortisol are measured over the following hour. Pituitary (Cushing's disease) tumors typically still respond to CRH with a rise in ACTH and cortisol, whereas ectopic ACTH sources and adrenal tumors usually do not — helping to localize the cause. The test is often combined with inferior petrosal sinus sampling for greater accuracy. Corticorelin is also used to assess pituitary ACTH reserve and, in research settings, to study the physiology of the HPA axis. Mechanistically it binds CRH receptors (CRHR1) on pituitary corticotroph cells, triggering ACTH release. Common transient effects after injection include facial flushing, a brief feeling of warmth, and occasionally a metallic taste or transient changes in blood pressure. It is administered by clinicians in a controlled setting with timed blood sampling, and the results are interpreted by an endocrinologist as one part of a broader diagnostic workup.