title: Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test.
abstract: OBJECTIVE
  The overnight dexamethasone (DXM) suppression test (DST) has high sensitivity, but moderate specificity, for diagnosing hypercortisolism. We have evaluated if simultaneous measurement of S-DXM may correct for variable DXM bioavailability and increase the diagnostic performance of DST, and if saliva (sa) is a feasible adjunct or alternative to serum.
  
  
  METHODS
  Prospective study of DST was carried out in patients with suspected Cushing's syndrome (CS) (n= 49), incidentaloma (n= 152) and healthy controls (n= 101). Cortisol, cortisone and DXM were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  
  
  RESULTS
  Three hundred and two subjects underwent DST; S-cortisol was ≥50 nmol/L in 83 patients, of whom 11 had CS and 27 had autonomous cortisol secretion. The lower 2.5 percentile of S-DXM in subjects with negative DST (n= 208) was 3.3 nmol/L, which was selected as the DXM cut-off level. Nine patients had the combination of low S-DXM and positive DST. Of these, three had been misdiagnosed as having autonomous cortisol secretion. DST results were highly reproducible and confirmed in a replication cohort (n= 58). Patients with overt CS had significantly elevated post-DST sa-cortisol and sa-cortisone levels compared with controls; 23 of 25 with autonomous cortisol secretion had elevated sa-cortisone and 14 had elevated sa-cortisol.
  
  
  CONCLUSIONS
  Simultaneous measurement of serum DXM and cortisol reduced false-positive DSTs by 20% and improved the specificity. S-DXM >3.3 nmol/L is sufficient for the suppression of cortisol <50 nmol/L. Measurement of glucocorticoids in saliva is a non-invasive and easy procedure and post-DST sa-cortisone was found particularly useful in the diagnosis of CS.
authors.affiliation: Department of Clinical ScienceUniversity of Bergen, Bergen, Norway.|Department of Medicine.|Department of the Hormone LaboratoryHaukeland University Hospital, Bergen, Norway.
authors.forename: Grethe Å
authors.initials: GÅ
authors.lastname: Ueland
authors.affiliation: Department of Clinical ScienceUniversity of Bergen, Bergen, Norway.|Department of Medicine.
authors.forename: Paal
authors.initials: P
authors.lastname: Methlie
authors.affiliation: Department of the Hormone LaboratoryHaukeland University Hospital, Bergen, Norway.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kellmann
authors.affiliation: Department of EndocrinologySt. Olav's Hospital, Trondheim, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Bjørgaas
authors.affiliation: Department of EndocrinologySt. Olav's Hospital, Trondheim, Norway.|Department of Public Health and General PracticeNorwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Bjørn O
authors.initials: BO
authors.lastname: Åsvold
authors.affiliation: Department of EndocrinologySt. Olav's Hospital, Trondheim, Norway.
authors.forename: Ketil
authors.initials: K
authors.lastname: Thorstensen
authors.affiliation: Department of EndocrinologyAkershus University Hospital, Lørenskog, Norway.
authors.forename: Oskar
authors.initials: O
authors.lastname: Kelp
authors.affiliation: Department of Medicine.
authors.forename: Hrafnkell B
authors.initials: HB
authors.lastname: Thordarson
authors.affiliation: Department of Clinical ScienceUniversity of Bergen, Bergen, Norway.|Department of the Hormone LaboratoryHaukeland University Hospital, Bergen, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
authors.affiliation: Department of Clinical ScienceUniversity of Bergen, Bergen, Norway.|Department of Medicine.
authors.forename: Kristian
authors.initials: K
authors.lastname: Løvås
authors.affiliation: Department of Clinical ScienceUniversity of Bergen, Bergen, Norway.|Department of Medicine.
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000378:metabolism; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003348:Cortisone / Q000378:metabolism*; D003480:Cushing Syndrome / Q000175:diagnosis* / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D033162:Incidental Findings; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012463:Saliva / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D003907:Dexamethasone; D003348:Cortisone; D006854:Hydrocortisone