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The Ovine Corticotropin-Releasing Hormone (CRH) Stimulation Test Is Superior to the Human CRH Stimulation Test for the Diagnosis of Cushing's Disease

Developmental Endocrinology Branch, National Institute of Child Health and Human Development Bethesda, Maryland 20892
Clinical Neurosurgery Section, the Surgical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke Bethesda, Maryland 20892
National Institutes of Health Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. Lynnette Nieman, Building 10, Room 10N262, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892.

The ovine CRH (oCRH) stimulation test is useful in distinguishing Cushing's disease from the syndrome of ectopic ACTH secretion. Most patients with Cushing's disease have increased plasma ACTH and cortisol responses to oCRH, while patients with the ectopic ACTH syndrome do not. We predicted that the homologous hormone human CRH (hCRH) might be an equally useful diagnostic agent, with the theoretic advantage of being less immunogenic. This study compared the responses to hCRH and oCRH (1 µg/kg, iv) in 15 patients with Cushing's disease. Plasma ACTH and cortisol levels increased in most patients during the first hour after administration of either hCRH or oCRH. However, the peak and time-integrated hormonal responses to hCRH were smaller than the responses to oCRH. All but 1 patient had an ACTH and/or cortisol response to oCRH that exceeded 4 times the intraassay coefficient of variation. Three patients had neither an ACTH nor a cortisol response to hCRH by the same criterion. Thus, when administered at equivalent doses, hCRH is a less effective stimulus of ACTH and cortisol secretion in patients with Cushing's disease. Based upon the observation that the oCRH stimulation test has greater sensitivity than the hCRH stimulation test for the diagnosis of Cushing's disease, we conclude that oCRH is the preferred analog to use for CRH testing in patients with Cushing's syndrome.

Received November 2, 1988.

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