Endocrine Abstracts (2002) 3 P274

What value do cortisol measurements provide in monitoring metyrapone therapy?

G Wieringa1, S Naing1, LA Perry2, JM Anderson1, K Wiener3, GC Burrows4, R Warburton5, JW Kane6 & PJ Trainer1


1Departments of Endocrinology and Biochemistry, Christie Hospital, Manchester, UK; 2Chemical Pathology, St Bartholomews, London, UK; 3North Manchester General Hospital, Manchester, UK; 4Stepping Hill Hospital, Stockport, UK; 5South Manchester University Hospitals Trust, Manchester, UK; 6Hope Hospital, Salford, UK.


Metyrapone is a potent inhibitor of the conversion of 11-deoxycortisol (11-DOC) to cortisol and is used in the treatment of Cushing's syndrome. This study has assessed the clinical significance of 11-DOC cross-reaction in five serum cortisol assays provided on automated immunoassay analysers. Cross-reaction was determined from the linear regression of increase in measured cortisol against increasing levels of 11-DOC (0, 1590, 4310, 6490, 7040 nmol/L) added to a serum pool. In addition, 11-DOC and serum cortisol were measured in 33 sera from 14 metyrapone treated patients (dose range 750 - 3750 mg/day). RESULTS: Slope values derived from linear regression data of increasing 11-DOC up to 4000 nmol/L against measured serum cortisol for each assay system varied considerably: 0.08 (Roche Elecsys), 0.16 (Bayer Immuno1), 0.27 (Wallac Delfia), 0.28 (Bayer ACS180) and 0.63 (Abbott TDx/F1X). Median 11-DOC in patients' samples was 593 nmmol/L (range 55 - 9650 nmol/L). The over-estimation in the reported cortisol result of each method was calculated by using slope values. Measured and adjusted serum cortisol levels at two representative 11 DOC levels are shown below:

11-DOC: At 236 nmol/L (Serum cortisol nmol/L)

Roche Elecsys: 467 measured, 448 adjusted

Bayer Immmuno-1: 478 measured, 441adjusted

Wallac DELFIA: 400 measured, 336 adjusted

Bayer CS 180: 474 measured, 407 adjusted

Abbott FlX/TdX: 657 measured, 509 adjusted

11-DOC: At 750 nmol/L

Roche Elecsys: 509 measured, 375 adjusted

Bayer Immmuno-1: 395 measured, 121adjusted

Wallac DELFIA: 505 measured, 36 adjusted

Bayer CS 180: 608 measured, 112 adjusted

Abbott FlX\/TdX: 655 measured, <0 adjusted

CONCLUSION: 11-DOC cross-reaction is a clinically significant and under-reported phenomenon. It leads to falsely high serum cortisol results and this may in turn lead to over-treatment with metyrapone and potentially hypo-adrenalism.

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