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oCRH Stimulation Test Protocols

Cushing's syndrome is a condition that results from exposure to high levels of the hormone cortisol, produced by the adrenal glands. The production of cortisol is dependent on the activity of the adrenocorticotropic hormone (ACTH). ACTH causes release of the Corticotropin Releasing Hormone (CRH), which in turn stimulates cortisol secretion. The physiological response to administration of ovine CRH is used in the United States to diagnose Cushing's syndrome, whereas European countries use human CRH for the test.

  1. Causes of Cushing's Syndrome

    • A benign tumor in the pituitary gland can cause excess secretion of ACTH, leading to greater cortisol levels. In some cases, a tumor in an organ such as the lungs, thyroid or pancreas that doesn't generally produce ACTH may cause an abnormal secretion of ACTH that elevates cortisol levels. Such tumors are called ectopic ACTH-secreting tumors. In a few cases, the excessive secretion of cortisol is a result of some disorder of the adrenal glands such as adrenal adenoma, and not due to stimulation by ACTH.

    Uses of oCRH Stimulation Test

    • The oCRH stimulation test is very useful in distinguishing Cushing's syndrome that is ACTH-dependent from that which is ACTH-independent. This test helps to identify the site from where the excess cortisol arises. It is based on the principle that patients with pituitary tumors respond to CRH stimulation, whereas those with ectopic ACTH-secreting tumors do not. Besides, this test also helps to distinguish the condition of pseudo-Cushing's syndrome, in which patients present the typical features of Cushing's syndrome, but these are unrelated to ACTH secretion.

    oCRH Test Protocol

    • In the oCRH test, a blood sample is first drawn to measure the baseline levels of ACTH and cortisol in the test subject. Next, ovine CRH is administered intravenously at a dose of 1 microgram per kilogram of body weight, up to a maximum of 100 micrograms. The entire dose is administered at one time over a period of one minute. One blood sample is immediately drawn and subsequent samples are drawn at 15, 30, 60, 90 and 120 minutes. The blood samples are tested for levels of ACTH and cortisol.

    Interpretation of Results

    • In normal individuals, soon after injection of oCRH, the plasma levels of ACTH rise rapidly and reach a maximum within the first 10 to 15 minutes following injection. The rise in levels of cortisol is slower, and peak values are obtained around 30 to 60 minutes after injection of oCRH. These levels slowly decrease over a period of two hours. In patients with Cushing's syndrome due to a pituitary tumor, there is a minimum 50 percent increase in levels of ACTH and 20 percent spike in cortisol levels in comparison with their baseline levels. In patients with Cushing's due to ectopic tumors, adrenal gland disorders and pseudo-Cushing's syndrome, the baseline levels of ACTH and cortisol remain unaffected by the administration of oCRH.

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