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Are serum cortisol measurements by immunoassays reliable?: A case series
Nowreen Haq1, Katherine A Araque2, Anastasia L Gant Kanegusuku3
1Division of Endocrinology and Metabolism. National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK). National Institutes of Health, Clinical Center. Bethesda, MD, United States of America.
Insights
Automated immunoassays may provide inaccurate thyroid hormone and serum cortisol measurements. High or low levels of binding globulins, such as thyroxine-binding globulin and corticosteroid binding globulin, can affect assay reliability.
Area of Science:
- Clinical Chemistry
- Endocrinology
- Assay Development
Background:
- Automated immunoassays (IA) are widely used for measuring various analytes, including hormones.
- Previous studies have indicated unreliable thyroid hormone measurements with IA in cases of abnormal thyroxine-binding globulin (TBG) levels.
- Many hormones circulate bound to specific binding proteins, which can potentially interfere with immunoassay accuracy.
Purpose of the Study:
- To investigate the accuracy of automated immunoassays for serum cortisol measurement.
- To compare IA-derived cortisol concentrations with those obtained by a reference method (liquid chromatography-tandem mass spectrometry).
- To identify potential factors affecting IA accuracy for serum cortisol.
Main Methods:
- Comparison of serum cortisol measurements obtained by routine automated immunoassays (IA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Analysis of preliminary data from a series of cases.
- Evaluation of the impact of corticosteroid binding globulin (CBG) levels on IA results.
Main Results:
- Automated immunoassays consistently reported falsely low serum cortisol concentrations, with an average underestimation of 27%.
- Preliminary findings suggest that high concentrations of corticosteroid binding globulin (CBG) interfere with IA measurements of serum cortisol.
- This interference leads to inaccurate low cortisol readings.
Conclusions:
- Routine automated immunoassays may not provide accurate serum cortisol measurements, particularly in the presence of elevated corticosteroid binding globulin.
- The findings highlight a potential limitation of IA for cortisol analysis, similar to issues observed with thyroid hormone assays.
- Further validation using LC-MS/MS is recommended for accurate cortisol quantification in clinical settings, especially when CBG levels are abnormal.
Abstract:
Routinely used automated immunoassays have been found to give unrealiable measurements of thyroid hormones in the presence of either high or low levels of thyroxine-binding globulin. Thyroid hormones are not the only analytes bound to specific binding proteins that are measured by immunoassays. Preliminary data from a series of cases, comparing IA measurements to those obtained by liquid chromatography-tandem mass spectrometry, reveal for the first time that IA measurements report falsely low (by an average of 27%) serum cortisol concentrations. Initial findings suggest that IA measurements of serum cortisol are affected by high concentrations of corticosteroid binding globulin.
