title: First-line screening tests for Cushing's syndrome in patients with adrenal incidentaloma: the role of urinary free cortisol measured by LC-MS/MS.
abstract: OBJECTIVE
  Patients with adrenal incidentaloma present a wide range of cortisol secretion, which is not always properly defined by first-line screening tests recommended to rule out Cushing's syndrome (CS), such as 1-mg dexamethasone suppression test (1-mg DST), late night salivary cortisol (LNSC), or 24-h urinary free cortisol (UFC). Therefore, we examined the diagnostic performance of each screening test in patients with adrenal incidentaloma.
  
  
  METHODS
  In a series of 164 consecutive patients with adrenal incidentaloma, we measured serum cortisol after 1-mg DST, LNSC, and UFC (with LC-MS/MS). Medical history was investigated for cardiovascular events (CVE) in a subgroup of 93 patients with at least 2 years of follow-up.
  
  
  RESULTS
  Serum cortisol <50 nmol/L after 1-mg DST presented the highest sensitivity (100%) to rule out CS, despite a low specificity (62%). UFC > 170 nmol/24 h achieved the highest diagnostic accuracy (sensitivity 98%, specificity 91%, and negative/positive likelihood ratios of 0.02/10.83, respectively). The prevalence of CVE was higher in patients with non-suppressed cortisol after 1-mg DST and high UFC levels (p = 0.018). Traditional cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia, BMI > 30 kg/m2, smoke or high gender-based waist circumference) were not associated with CVE.
  
  
  CONCLUSIONS
  The 1-mg DST at its lowest threshold presented high sensitivity in identifying CS, but its low specificity encourages us to consider UFC levels, measured with LC-MS/MS, to reduce false-positive test results. High UFC levels could also be considered as markers to stratify cardiovascular risk in patients with adrenal incidentaloma.
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, Padova University Hospital, Via Ospedale Civile, 105-35128, Padova, Italy. ceccato.filippo@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Ceccato
authors.affiliation: Laboratory Medicine Unit, Department of Medicine DIMED, Padova University Hospital, Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Antonelli
authors.affiliation: Biostatistics, Epidemiology and Public Health Unit, Department of Cardiac, Thoracic and Vascular Sciences, Padova University Hospital, Padova, Italy.
authors.forename: A C
authors.initials: AC
authors.lastname: Frigo
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, Padova University Hospital, Via Ospedale Civile, 105-35128, Padova, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Regazzo
authors.affiliation: Laboratory Medicine Unit, Department of Medicine DIMED, Padova University Hospital, Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Plebani
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, Padova University Hospital, Via Ospedale Civile, 105-35128, Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Boscaro
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, Padova University Hospital, Via Ospedale Civile, 105-35128, Padova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Scaroni
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000150:complications*; D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology; D002853:Chromatography, Liquid / Q000379:methods*; D003480:Cushing Syndrome / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D006854:Hydrocortisone
keywords: Adrenal incidentaloma; Cardiovascular risk; Liquid chromatography–tandem mass spectrometry; Metabolic syndrome; Urinary free cortisol