Cortisol measurement in patients receiving metyrapone therapy
Abstract
Current guidance recommends titrating the dose of metyrapone against serum cortisol concentration, in patients under medical management of Cushing's syndrome. In the UK, this almost always involves measuring serum cortisol concentration by immunoassay, the performance of which is questionable in the presence of altered steroid metabolism. Sera from two patients receiving metyrapone were analysed using a liquid chromatography tandem mass spectrometry (MS) steroid assay to identify which steroids, if any, were elevated in these patients. In addition, control serum was spiked with a series of steroids to identify any potential positive interferences in a cortisol immunoassay. Serum 11-deoxycortisol concentration was elevated in both of the patients studied. One patient also had an elevated serum 17-hydroxyprogesterone concentration and the other an elevated androstenedione. In addition, the results of the interference studies indicated that the cortisol immunoassay was susceptible to interference from 11-deoxycortisol, 17-hydroxyprogesterone and 21-deoxycortisol. However, the magnitude of interference, in the serum cortisol immunoassay, due to these three steroids could not account for the discrepancy between the cortisol concentrations measured by immunoassay and those measured by MS. Both clinicians and laboratory staff should be aware of these interferences when monitoring patients undergoing treatment with metyrapone, and consequently serum should be measured in these patients by MS, not by immunoassay.
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Immunoassay cortisol measurements in patients taking metyrapone show a positive bias relative to a routine LC-MS/MS assay.
“Immunoassay cortisol measurements in patients taking metyrapone have also been reported to display a positive bias relative to a routine LC-MS/MS assay (10,11 ).”
From Serum cortisol: an up-to-date assessment of routine assay performance (2016) · cites this paper as [11]
The first generation Roche E170 and Siemens Centaur XP assays were particularly prone to over-estimation in the metyrapone cohort, likely secondary to antibody cross-reactivity with cortisol precursors.
“Of these, the first generation Roche E170 and Siemens Centaur XP were particularly prone to over-estimation, likely secondary to antibody cross-reactivity with cortisol precursors (10,11 ).”
From Serum cortisol: an up-to-date assessment of routine assay performance (2016) · cites this paper as [11]
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Daniel, E., Aylwin, S., Mustafa, O., Ball, S., Munir, A., Boelaert, K., Chortis, V., Cuthbertson, D. J., Daousi, C., Rajeev, S. P., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2616 · Cited by 231 · see citing works
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Self-citationSerum cortisol: an up-to-date assessment of routine assay performance
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- Authors
- Owen, L. J., Halsall, D. J., & Keevil, B. G.
- Affiliations
- Biochemistry Department, University Hospital of South Manchester, Manchester M23 9LT
- Addenbrooke's Hospital (GB)
- Corresponding author
- Owen, L J
- ORCID
- Keevil, B G
- Venue
- Annals of Clinical Biochemistry International Journal of Laboratory Medicine
- Publisher
- SAGE Publications
- Published
- 2010-10-06
- Volume
- 47
- Issue
- 6
- Pages
- 573-575
- ISSN
- 0004-5632 (ISSN-L)
- 1758-1001
- OpenAlex
- W2331627373
- Cited by
- 37
- References
- 6
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 5 · 2013: 7 · 2012: 2
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Clinical Biochemistry International Journal of Laboratory Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- metyrapone, Cushing's syndrome, 11-deoxycortisol, 17-hydroxyprogesterone, androstenedione, 21-deoxycortisol, steroid assay, dose titration
- MeSH terms
- Chromatography, Liquid, Cushing Syndrome, Humans, Hydrocortisone, Immunoassay, Metyrapone, Mass Spectrometry
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