Endocrine Abstracts

Background: The displacement of cortisol from its binding globulin (CBG) in the Abbott Alinity immunoassay assumes an average concentration of CBG in all individuals. Displacement buffer volume, and/or composition, is frequently insufficient to displace cortisol where higher concentrations of CBG are present (e.g. with higher oestrogen concentrations). To address this bias, the Eastern Pathology Alliance (EPA) introduced a 1:2 dilution step on all serum cortisol specimens in December 2021. Diluting the specimen, prior to the displacement step, markedly improved the recovery seen in neat specimens.

Methods: External quality assessment (EQA) specimens, with known concentrations of cortisol (established via liquid chromatography-mass spectrometry (LC-MS)), were used to examine the impact of automatic dilution on expected results, irrespective of gender. Serum EQA pools (8 males, 6 females, and 3 pregnant females) were analysed, in duplicate, neat and diluted (1:2), and compared with the LC-MS target concentrations. Patient specimens (106 males, 95 females, and 106 pregnant females) were analysed neat and diluted to assess any potential clinical impact of this change.

Results: Post-dilution step patient specimen recovery, compared to the neat result, for males, females and pregnant females was 108%, 110% and 116% respectively. Recovery was concentration-dependent, with little change seen in patient samples at cortisol concentrations <200 nmol/l.

Conclusions: Introduction of an automatic dilution step to the Abbott Alinity immunoassay for serum cortisol analysis has corrected an inherent gender-related bias in the assay design. The concentration-dependence of the recovery ensures that patients at risk of adrenal insufficiency are investigated appropriately. Therefore, the change averts potential over-investigation, without compromising the clinical utility of the analysis.