ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 25 P36

Comparison of serum cortisol measurement by immunoassay and liquid chromatography-tandem mass spectrometry in patients receiving the 11[beta]-hydroxylase inhibitor metyrapone

Phillip Monaghan1, Laura Owen2, Peter Trainer1, Georg Brabant1, Brian Keevil2 & Denise Darby1


1The Christie NHS Foundation Trust, Manchester, UK; 2University Hospital of South Manchester, Manchester, UK.


The accurate measurement of cortisol by immunoassay is compromised by the potential for cross-reactivity of reagent antibodies with structurally-related steroid compounds present in patient serum. This susceptibility is potentiated when normal steroid metabolism is altered pharmacologically by anti-steroidogenic drugs. This class of drug is utilised in the management of Cushing’s syndrome to moderate cortisol production. To investigate the effect of the 11β-hydroxylase inhibitor metyrapone on serum cortisol assay, a comparison of measurement by immunoassay versus liquid chromatography–tandem mass spectrometry (LC–MS/MS) as gold standard was conducted.

Cortisol was measured in serum from three patient groups; i) patients receiving metyrapone therapy (n=112), ii) control group of patients diagnosed with Cushing’s syndrome currently receiving no treatment (n=32) and iii) control group of normal patients with no known adrenal pathology and not receiving medication known to interfere in the immunoassay of cortisol (n=79).

Bland-Altman plots showed good agreement between methods for the normal control group (bias=+2.5% (4.4 nmol/l)) and Cushing’s control group (bias=+1.3% (3.5 nmol/l)). This was in contrast to the metyrapone therapy group (bias=−23% (−59 nmol/l)). Passing-Bablok linear regression revealed bias observations were constant in nature with minimal contribution from proportional error. Pearson correlation coefficients for the three patients groups were ρ=0.39*, 0.17 and 0.36* for the normal control, Cushing’s control and metyrapone therapy groups, respectively (*indicates Pearson correlation coefficient significant at P<0.05). LC–MS/MS results were positively correlated with the difference. Further interrogation of metyrapone group data showed the degree of difference between LC–MS/MS versus immunoassay positively correlated with dose. This trend was also noted for serum 11-deoxycortisol concentration with dose.

In conclusion, these data show that the liability of immunoassay measurement of serum cortisol to interference in patients receiving metyrapone may lead to erroneous clinical decisions concerning dose titration.

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