Ann Lab Med.  2020 Jul;40(4):285-296. 10.3343/alm.2020.40.4.285.

Cortisol Measurements in Cushing's Syndrome: Immunoassay or Mass Spectrometry?

• Casals G
• Hanzu FA

• KMID: 2470324
• DOI: http://doi.org/10.3343/alm.2020.40.4.285

Abstract

Determination of cortisol levels in the urine (24 hours urine free cortisol), saliva (late-night), or serum (total cortisol after dexamethasone suppression) is recommended to screen for Cushing's syndrome (CS). This review focuses on the differences between the frequently used cortisol-antibody immunoassay-based methods and the highly specific mass-spectrometry-based methods that are progressively being employed in clinical laboratories for CS screening. The particular characteristics of cortisol metabolism and the lack of specificity of the immunoassays cause marked differences between both methods that are in turn highly dependent on the biological matrix, in which the cortisol is measured. Understanding the origin of these differences is essential for the interpretation of these results. Although cross-reactivity with endogenous steroids leads to grossly inaccurate results of immunoassay measurements of cortisol in the saliva and urine, preliminary evidence suggests that the clinical sensitivity of CS screening using immunoassays may be similar to CS screening using mass spectrometry. However, mass spectrometry offers more accurate results and considerably reduced variation across laboratories, while avoiding false-positive results. Moreover, mass spectrometry can overcome some common diagnostic challenges, such as identification of exogenous corticosteroids or simultaneous assessment of appropriate dexamethasone levels in suppression tests. Further, comprehensive mass spectrometry-based profiling of several steroid metabolites may be useful for discriminating among different subtypes of CS. Finally, this review discusses the main preanalytical factors that could cause variations in cortisol measurements and their influence on the reliability of the results.

Keyword

Cortisol; Immunoassay; Mass spectrometry; Sensitivity

MeSH Terms

Adrenal Cortex Hormones
Cushing Syndrome*
Dexamethasone
Hydrocortisone*
Immunoassay*
Mass Screening
Mass Spectrometry*
Metabolism
Saliva
Sensitivity and Specificity
Steroids
Adrenal Cortex Hormones
Dexamethasone
Hydrocortisone
Steroids

Figure

• 

  Fig. 1 Representation of the bias introduced by immunoassays in UFC measurements in 10 healthy control subjects and 10 patients with CS (unpublished data). UFC was simultaneously measured by an immunoassay, as described previously (Liaison, Diasorin, Italy), and GC-MS. The mean positive biases introduced by the immunoassay in all healthy control subjects and CS patients were determined to be 121% (range: 44–219%; N=33) and 135% (range: 33–344%; N=35), respectively. Abbreviations: UFC, urinary free cortisol; CS, Cushing's syndrome; GC-MS, gas chromatography-mass spectrometry.

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