The diagnostic performance of urinary free cortisol is better than the cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC–MS/MS method in routine clinical practice

• Published in: European journal of endocrinology Vol. 171; no. 1; pp. 1 - 7
• Main Authors: Ceccato, Filippo, Antonelli, Giorgia, Barbot, Mattia, Zilio, Marialuisa, Mazzai, Linda, Gatti, Rosalba, Zaninotto, Martina, Mantero, Franco, Boscaro, Marco, Plebani, Mario, Scaroni, Carla
• Format: Journal Article
• Language: English
• Published: Bristol Bioscientifica Ltd 01.07.2014; BioScientifica
• Subjects: Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adult; Biological and medical sciences; Chromatography, Liquid - methods; Clinical Study; Cortisone - urine; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Glucocorticoids - urine; Humans; Hydrocortisone - urine; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pituitary ACTH Hypersecretion - diagnosis; Pituitary ACTH Hypersecretion - urine; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Tandem Mass Spectrometry - methods; Vertebrates: endocrinology; Endocrinopathy; Performance evaluation; Adrenal cortex diseases; Methodology; Hyperadrenocorticism; Cortisol; Hydrocortisone; Glucocorticoid; Adrenal gland diseases; Ratio; Diagnosis; Urine; Corticosteroid; Steroid hormone; Use; Antiinflammatory agent; Cushing syndrome; Liquid chromatography; Medical screening; De novo; Cortisone; Professional practice; Mass spectrometry MS/MS; Adrenal hormone; Performance; Endocrinology
• ISSN: 0804-4643; 1479-683X; 1479-683X
• DOI: 10.1530/EJE-14-0061

ObjectiveThe Endocrine Society Clinical Guidelines recommend measuring 24-h urinary free cortisol (UFF) levels using a highly accurate method as one of the first-line screening tests for the diagnosis of Cushing's Syndrome (CS). We evaluated the performance of UFF, urinary free cortisone (UFE), and the UFF:UFE ratio, measured using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method.Subjects and methodsThe LC–MS/MS was used to analyze UFF and UFE levels in 43 surgically confirmed CS patients: 26 with Cushing's disease (CD, 16 de novo and ten recurrences), 11 with adrenal CS and six with ectopic CS; 22 CD patients in remission; 14 eu-cortisolemic CD patients receiving medical therapy; 60 non-CS patients; and 70 healthy controls. Sensitivity and specificity were determined in the combined groups of non-CS patients, healthy controls, and CD in remission.ResultsUFF>170 nmol/24 h showed 98.7% specificity and 100% sensitivity for de novo CS, while sensitivity was 80% for recurrent CD patients, who were characterized by lower UFF levels. The UFF:UFE and UFF+UFE showed lower sensitivity and specificity than UFF. Ectopic CS patients had the highest UFF and UFF:UFE levels, which were normal in the CD remission patients and in those receiving medical therapy.ConclusionsOur data suggest high diagnostic performance of UFF excretion measured using LC–MS/MS, in detecting de novo CS. UFF:UFE and UFF+UFE assessments are not useful in the first step of CS diagnosis, although high levels were found to be indicative of ectopic CS.