title: 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.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  UFF>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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ceccato
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Antonelli
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbot
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Zilio
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Mazzai
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Gatti
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Zaninotto
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Mantero
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Boscaro
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, ItalyEndocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.affiliation: Endocrinology UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyLaboratory Medicine UnitDepartment of Medicine DIMED, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, ItalyEndocrinology UnitUniversity-Hospital of Padova, via Ospedale Civile 105, 35128 Padova, ItalyDepartment of Laboratory Medicine,University-Hospital of Padovavia Giustiniani 2, 35128 Padova, Italy carla.scaroni@unipd.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Scaroni
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods*; D003348:Cortisone / Q000652:urine*; D005260:Female; D005938:Glucocorticoids / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000175:diagnosis* / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D005938:Glucocorticoids; D003348:Cortisone; D006854:Hydrocortisone