Pseudo-Cushing syndrome caused by fenofibrate interference with urinary cortisol assayed by high-performance liquid chromatography

J Clin Endocrinol Metab. 2003 Aug;88(8):3521-4. doi: 10.1210/jc.2003-030234.


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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid
  • Cushing Syndrome / diagnosis*
  • Cushing Syndrome / urine
  • Diagnosis, Differential
  • Female
  • Fenofibrate / adverse effects*
  • Fenofibrate / therapeutic use
  • Humans
  • Hydrocortisone / urine*
  • Hyperlipidemias / drug therapy
  • Hypolipidemic Agents / adverse effects*
  • Hypolipidemic Agents / therapeutic use
  • Mass Spectrometry
  • Middle Aged
  • Obesity / complications
  • Radioimmunoassay


  • Hypolipidemic Agents
  • Fenofibrate
  • Hydrocortisone