Clinical implications for biochemical diagnostic thresholds of adrenal sufficiency using a highly specific cortisol immunoassay

• Published in: Clinical biochemistry 2017-06, Vol.50 (9), p.475-480
• Main Authors: Kline, GA, Buse, J, Krause, RD
• Format: Article
• Language: English
• Subjects: Addison's disease; Adolescent; Adrenal disease; Adrenal insufficiency; Adrenal Insufficiency - blood; Adrenal Insufficiency - diagnosis; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Clinical Laboratory Techniques - instrumentation; Clinical Laboratory Techniques - methods; Cortisol; Female; Humans; Hydrocortisone - blood; Immunoassay - instrumentation; Immunoassay - methods; Infant; Infant, Newborn; Male; Middle Aged
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2017.02.008

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. 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). 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. 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. 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. •Guidelines for interpretation of tests of adrenal insufficiency are rarely method-specific.•A highly specific immunoassay for cortisol gives much lower cortisol levels than older methods.•Diagnostic criteria must be validated in patients actually suspected of disease.•A Roche Cortisol II of >350nmol/L effectively rules out adrenal insufficiency.•This new threshold differs from the traditional 500nmol/L cited in most guidelines.