This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lin, C.-L. Articles by Kao, P. C. Search for Related Content PubMed PubMed Citation Articles by Lin, C.-L. Articles by Kao, P. C.

Urinary Free Cortisol and Cortisone Determined by High Performance Liquid Chromatography in the Diagnosis of Cushing’s Syndrome¹

Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Pai C. Kao, Ph.D., Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.

To determine the efficacy of cortisol and its metabolite, cortisone, measured simultaneously by high performance liquid chromatography (HPLC) in the diagnosis of Cushing’s syndrome, we retrospectively reviewed the histories of 29 surgically proven Cushing’s syndrome patients (20 Cushing’s disease, 5 ectopic ACTH syndrome, and 4 adrenal Cushing’s syndrome) and 6 patients with exogenous Cushing’s syndrome. These 35 patients had urinary free cortisol determined by both HPLC and competitive binding methods. The efficacy of the HPLC assay using cortisol alone was equivalent to that of the competitive binding assay; 22 of 29 (76%) patients had increased cortisol. Cortisone also aided in the diagnosis; 25 of 29 (86%) had increased cortisone. Twenty-seven of the 29 (93%) patients had either both cortisone and cortisol (n = 19) or at least 1 of the 2 (n = 8) increased. All 6 patients with exogenous Cushing’s syndrome had suppressed urinary free cortisol, cortisone, and the presence of prednisone and prednisolone. In the competitive binding assay, all exogenous Cushing’s patients had falsely increased cortisol results.

In conclusion, urinary free cortisol plus cortisone determined simultaneously by HPLC added a new dimension to the diagnosis of Cushing’s syndrome. It should be considered when exogenous Cushing’s syndrome is suspected or when only one urinary cortisol test is allowed to be ordered.

This article has been cited by other articles:

				M. Boscaro and G. Arnaldi Approach to the Patient with Possible Cushing's Syndrome J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3121 - 3131. [Abstract] [Full Text] [PDF]

				L. Wood, D. H Ducroq, H. L Fraser, S. Gillingwater, C. Evans, A. J Pickett, D. W Rees, R. John, and A. Turkes Measurement of urinary free cortisol by tandem mass spectrometry and comparison with results obtained by gas chromatography-mass spectrometry and two commercial immunoassays Ann Clin Biochem, July 1, 2008; 45(4): 380 - 388. [Abstract] [Full Text] [PDF]

				L. K. Nieman, B. M. K. Biller, J. W. Findling, J. Newell-Price, M. O. Savage, P. M. Stewart, and V. M. Montori The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1526 - 1540. [Abstract] [Full Text] [PDF]

				T. Remer, T. Dimitriou, and C. Maser-Gluth Renal Net Acid Excretion and Plasma Leptin Are Associated with Potentially Bioactive Free Glucocorticoids in Healthy Lean Women J. Nutr., February 1, 2008; 138(2): 426S - 430S. [Abstract] [Full Text] [PDF]

				T. Remer and C. Maser-Gluth Simultaneous Measurements of Urinary Free Cortisol and Cortisone for the Assessment of Functional Glucocorticoid Activity Clin. Chem., October 1, 2007; 53(10): 1870 - 1871. [Full Text] [PDF]

				J. W. Findling and H. Raff Cushing's Syndrome: Important Issues in Diagnosis and Management J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3746 - 3753. [Abstract] [Full Text] [PDF]

				M. Fenske How Much "Urinary Free Cortisol" Is Really Cortisol during Water Diuresis in Healthy Individuals? Clin. Chem., June 1, 2004; 50(6): 1102 - 1104. [Full Text] [PDF]

				M. N. Kerstens, F. G. H. van der Kleij, A. H. Boonstra, W. J. Sluiter, J. Koerts, G. Navis, and R. P. F. Dullaart Salt Loading Affects Cortisol Metabolism in Normotensive Subjects: Relationships with Salt Sensitivity J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4180 - 4185. [Abstract] [Full Text] [PDF]

				H. Raff and J. W. Findling A Physiologic Approach to Diagnosis of the Cushing Syndrome Ann Intern Med, June 17, 2003; 138(12): 980 - 991. [Full Text] [PDF]

				R. L. Taylor, D. Machacek, and R. J. Singh Validation of a High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Method for Urinary Cortisol and Cortisone Clin. Chem., September 1, 2002; 48(9): 1511 - 1519. [Abstract] [Full Text] [PDF]

				T. Remer, A. Neubert, and C. Maser-Gluth Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research Am. J. Clinical Nutrition, March 1, 2002; 75(3): 561 - 569. [Abstract] [Full Text] [PDF]

				P. C. Kao, D. A. Machacek, M. J. Magera, J. M. Lacey, and P. Rinaldo Diagnosis of Adrenal Cortical Dysfunction by Liquid Chromatography-Tandem Mass Spectrometry Ann. Clin. Lab. Sci., April 1, 2001; 31(2): 199 - 204. [Abstract] [Full Text] [PDF]

				B. E. P. Murphy How Much ""UFC"" Is Really Cortisol? Clin. Chem., June 1, 2000; 46(6): 793 - 794. [Full Text] [PDF]

				B. E. P. Murphy Lack of Specificity of Urinary Free Cortisol Determinations: Why Does It Continue? J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2258a - 2259. [Full Text]

				J. Newell-Price, P. Trainer, M. Besser, and A. Grossman The Diagnosis and Differential Diagnosis of Cushing's Syndrome and Pseudo-Cushing's States Endocr. Rev., October 1, 1998; 19(5): 647 - 672. [Abstract] [Full Text]

				M. V. Mericq and G. B. Cutler Jr. High Fluid Intake Increases Urine Free Cortisol Excretion in Normal Subjects J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 682 - 684. [Abstract] [Full Text]