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Pseudo-Cushing Syndrome Caused by Fenofibrate Interference with Urinary Cortisol Assayed by High-Performance Liquid Chromatography

Departments of Medicine and Pathology (A.W.M.), University of Utah, Salt Lake City, Utah 84132; Endocrine-Diabetes Center (J.F.), St. Luke’s Medical Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53215; and Associated Regional and University Pathologists Institute for Clinical and Experimental Pathology (M.M.K., A.L.R., G.J.N., A.H.T.), Salt Lake City, Utah 84108

Address all correspondence and requests for reprints to: A. Wayne Meikle, M.D., Associated Regional and University Pathologists, 500 Chipeta Way, Salt Lake City, Utah 84108. E-mail: wayne.meikle{at}hsc.utah.edu.

Urinary free cortisol (UFC) excretion over 24 h reflects the production rate of cortisol and is used commonly in the diagnosis of Cushing syndrome. We report on two patients evaluated for Cushing syndrome who had elevated UFC when analyzed by HPLC but normal values for the analysis performed by RIA and HPLC-mass spectrometry/mass spectrometry (HPLC-MS/MS). Other laboratory testing was inconsistent with the diagnosis of Cushing syndrome and raised doubts about the diagnosis. We identified a probable cause of analytical interference as coming from fenofibrate (Tricor), medication taken by the patients. Fenofibrate peak overlapped with the HPLC peak of cortisol and produced an MS/MS transition overlapping the major transition of cortisol. A second MS/MS transition was free from interference. In summary, fenofibrate administration may cause false elevation of UFC values determined by HPLC or HPLC-MS/MS in patients evaluated for Cushing syndrome. An HPLC-MS/MS method using multiple mass transitions, rather than a single transition, allows accurate quantitation of urinary cortisol in patients taking fenofibrate.

Abbreviations: MS/MS, Mass spectrometry/mass spectrometry; UFC, urinary free cortisol.

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