Corticotropin-releasing factor (CRF): stimulation in normal controls and in patients with Cushing's syndrome |
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| Authors: | O A Müller J Hartwimmer A Hauer T Kaliebe J Schopohl G K Stalla K von Werder |
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| Institution: | 1. E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk, Russia;2. EPD Research, Caesarea, Israel;3. Florida Hospital, Orlando, Florida;4. Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin;6. Hobart Group Capital, Geneva, Switzerland;1. Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany;2. Division of Genetic and Reproductive Toxicology, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany;1. Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium;2. Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium;3. Department of Respiratory Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium;1. Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States;2. Departments of Orthopaedic Surgery and Genetics, and the Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 United States |
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| Abstract: | Synthetic ovine and human CRF were given as an i.v. bolus to six healthy volunteers in four and two different dosages, respectively (oCRF: 25, 50, 100 and 200 micrograms; hCRF: 50 and 100 micrograms). There was a significant increase of ACTH and cortisol after the injection of all dosages though the dose-response relationship was only significant between the 50 and 100 micrograms dose of oCRF. No significant differences between ACTH and cortisol secretion after oCRF and hCRF were observed. Repetitive stimulation by hCRF led to repetitive release of identical amounts of ACTH. The CRF test with the 100 micrograms dosage was used in patients with proven Cushing's syndrome (n = 30). Results showed that the CRF test is useful in making the differential diagnosis of established Cushing's syndrome. In patients with ACTH-dependent Cushing's disease (n = 21), normal or elevated basal ACTH levels were significantly higher after stimulation by CRF compared to normal controls, with one exception. The pattern of cortisol secretion after CRF administration corresponded to the pattern of ACTH secretion in these patients. In two patients with ectopic ACTH syndrome, extremely elevated ACTH and cortisol levels did not change or showed only a small increase after CRF administration. In patients with unilateral adrenal adenoma or carcinoma (n = 7), suppressed ACTH levels did not rise after CRF administration. In addition, no significant change in cortisol secretion could be observed. After surgical removal of cortisol-producing adrenal tumors, the ACTH response to CRF can be demonstrated when cortisol levels are still undetectable. Pulsatile administration of CRF in one patient after unilateral adrenalectomy revealed that ACTH responses to CRF normalize rapidly but cannot be sustained if CRF administration is withdrawn, suggesting that the cause of adrenal failure after unilateral adrenalectomy for Cushing's syndrome or with long-term corticoid therapy is due to hypothalamic CRF deficiency. The suppression of ACTH responses to CRF in glucocorticoid-treated patients correlated with the daily corticoid dosage. Since the ACTH hyper-response to CRF in six patients with Cushing's disease was suppressed by short-term dexamethasone treatment, the pituitary as a target site for feedback inhibition also was demonstrated. |
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