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5 August 2003 | Volume 139 Issue 3 | Pages 194-204
Background: The cosyntropin stimulation test is the initial endocrine evaluation of suspected primary or secondary adrenal insufficiency.
Purpose: To critically review the utility of the cosyntropin stimulation test for evaluating adrenal insufficiency.
Data Sources: The MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency.
Study Selection: Studies with fewer than 5 persons with primary or secondary adrenal insufficiency or with fewer than 10 persons as normal controls were excluded. For secondary adrenal insufficiency, only studies that stratified participants by integrated tests of adrenal function were included.
Data Extraction: Summary receiver-operating characteristic (ROC) curves were generated from all studies that provided sensitivity and specificity data for 250-µg and 1-µg cosyntropin tests; these curves were then compared by using area under the curve (AUC) methods. All estimated values are given with 95% CIs.
Data Synthesis: At a specificity of 95%, sensitivities were 97%, 57%, and 61% for summary ROC curves in tests for primary adrenal insufficiency (250-µg cosyntropin test), secondary adrenal insufficiency (250-µg cosyntropin test), and secondary adrenal insufficiency (1-µg cosyntropin test), respectively. The area under the curve for primary adrenal insufficiency was significantly greater than the AUC for secondary adrenal insufficiency for the high-dose cosyntropin test (P < 0.001), but AUCs for the 250-µg and 1-µg cosyntropin tests did not differ significantly (P > 0.5) for secondary adrenal insufficiency. At a specificity of 95%, summary ROC analysis for the 250-µg cosyntropin test yielded a positive likelihood ratio of 11.5 (95% CI, 8.7 to 14.2) and a negative likelihood ratio of 0.45 (CI, 0.30 to 0.60) for the diagnosis of secondary adrenal insufficiency.
Conclusions: Cortisol response to cosyntropin varies considerably among healthy persons. The cosyntropin test performs well in patients with primary adrenal insufficiency, but the lower sensitivity in patients with secondary adrenal insufficiency necessitates use of tests involving stimulation of the hypothalamus if the pretest probability is sufficiently high. The operating characteristics of the 250-µg and 1-µg cosyntropin tests are similar.
Author and Article Information
From New Mexico Veterans Administration Health Care System and University of New Mexico, Albuquerque, New Mexico; Santa Clara Valley Medical Center, San Jose, California; and Stanford University, Palo Alto, California.
Acknowledgments: The authors thank Wolfgang Oelkers, MD, and coworkers for generously providing raw data used to develop the ROC curves in the Appendix Figure. The authors also thank Eunice Koefod and Edna McVey for their assistance in preparing the manuscript; Dale Kennedy for preparing the original figures; and Alan Garber, MD, PhD, for his critical comments.
Grant Support: By a grant from the Office of Research and Development, Medical Research Service, U.S. Department of Veterans Affairs, Washington, DC.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Richard Dorin, MD, Division of Endocrinology and Metabolism, New Mexico Veterans Administration Health Care System, Medical Service 111, 1501 San Pedro Boulevard SE, Albuquerque, NM 87108; e-mail, rdorin{at}salud.unm.edu.
Current Author Addresses: Dr. Dorin: Division of Endocrinology and Metabolism, New Mexico Veterans Administration Health Care System, Medical Service 111, 1501 San Pedro Boulevard SE, Albuquerque, NM 87108.
Dr. Qualls: Department of Mathematics and Statistics, General Clinical Research Center, University of New Mexico Hospital, 5-North, Camino de Salud, University of New Mexico, Albuquerque, NM 87131.
Dr. Crapo: Division of Endocrinology and Metabolism, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, CA 95128. ACADEMIA AND CLINIC
COMMON DIAGNOSTIC TESTS
Series Editors: Alan Garber, MD, PhD, and Harold Sox, MD
Diagnosis of Adrenal Insufficiency
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