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

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.