title: Clinical implications for biochemical diagnostic thresholds of adrenal sufficiency using a highly specific cortisol immunoassay.
abstract: OBJECTIVE
  Recent guidelines recommend a diagnosis of adrenal insufficiency when a stimulated peak cortisol level falls below 500nmol/L. This may not be valid using a highly specific cortisol immunoassay or liquid chromatography-mass spectroscopy (LCMS/MS). We sought to determine the diagnostic threshold for adrenal insufficiency using a new and widely available, highly specific cortisol immunoassay.
  
  
  METHODS
  All patients having a dynamic test of adrenal reserve had results measured using the historical cortisol assay (Roche Cortisol) and the newer assay (Roche Cortisol II).
  
  
  METHODS
  Subjects were categorized according to the traditional assay (normal>500nmol/L) with clinical case adjudication where necessary. Results from Cortisol II assay were concomitantly measured along with cortisol levels measured by LCMS/MS. ROC curve analysis was performed to generate new diagnostic thresholds.
  
  
  RESULTS
  The Roche Cortisol II compared favourably with measures by LCMS/MS, generating cortisol levels approximately 30% lower than the older immunoassay. Many normal subjects had peak cortisols as low as 300nmol/L with Cortisol II. The optimized diagnostic threshold for adrenal insufficiency was 350nmol/L with a sensitivity of 91% and specificity 97%. Use of the old diagnostic threshold with the Cortisol II assay would have inappropriately doubled the rate of patient-classification as adrenal insufficient.
  
  
  CONCLUSIONS
  Transition to a more specific cortisol assay requires revision of diagnostic thresholds for dynamic tests of adrenal insufficiency. With the Roche Cortisol II assay, a cut-off of 350nmol/L should replace the traditional 500nmol/L although some healthy subjects may be very close to this level.
authors.affiliation: Department of Medicine (Endocrinology), University of Calgary, Canada. Electronic address: Gregory.kline@albertahealthservices.ca.
authors.forename: G A
authors.initials: GA
authors.lastname: Kline
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary Laboratory Services, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Buse
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary Laboratory Services, Canada.
authors.forename: R D
authors.initials: RD
authors.lastname: Krause
mesh_terms: D000293:Adolescent; D000309:Adrenal Insufficiency / Q000097:blood* / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D019411:Clinical Laboratory Techniques / Q000295:instrumentation* / Q000379:methods*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007118:Immunoassay / Q000295:instrumentation / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged
chemical_list: D006854:Hydrocortisone
keywords: Addison's disease; Adrenal disease; Adrenal insufficiency; Cortisol