Corticorelin

Corticorelin is a synthetic 41-amino acid peptide corresponding to ovine (sheep) corticotropin-releasing hormone (CRH). While human CRH differs from ovine CRH by 7 amino acids, the ovine form was selected for clinical development because it has a longer plasma half-life and produces a more robust and prolonged ACTH response than human CRH in diagnostic testing. Corticorelin is used as a diagnostic agent in the differential diagnosis of ACTH-dependent Cushing's syndrome.

Cushing's syndrome caused by ACTH excess can originate from either a pituitary adenoma (Cushing's disease, approximately 70% of cases) or ectopic ACTH production by non-pituitary tumors (approximately 15-20% of cases). Distinguishing between these two sources is critical because the treatment differs dramatically — transsphenoidal surgery for pituitary disease versus localization and resection of the ectopic tumor.

The CRH stimulation test exploits the fact that pituitary corticotroph adenomas typically retain some responsiveness to CRH stimulation, while ectopic ACTH-producing tumors generally do not. After corticorelin injection, patients with Cushing's disease typically show a significant increase in ACTH and cortisol, while those with ectopic ACTH syndrome usually show little or no response. The criterion of a >35-50% increase in ACTH or >20% increase in cortisol from baseline has been used to distinguish pituitary from ectopic sources.

When combined with inferior petrosal sinus sampling (IPSS), the CRH stimulation test achieves very high diagnostic accuracy (>95%) for localizing the source of ACTH excess. During IPSS, blood samples are collected from the petrosal sinuses (which drain the pituitary) and a peripheral vein simultaneously, before and after CRH stimulation. A central-to-peripheral ACTH gradient >3:1 after CRH confirms a pituitary source.