Commercial Radioimmunoassays Do Not Measure Urinary Free Cortisol Accurately and Should Not Be Used for Physiological Studies

Beverley E. Pearson Murphy

Departments of Medicine, Obstetrics and Gynecology, and Psychiatry McGill University Montreal H3G 1A4, Canada

Address correspondence to: Dr. Beverley E. Pearson Murphy, Division of Endocrinology, Montreal General Hospital, 1650 Cedar, Montreal 83G IA4, Canada. E-mail: bev.murphy{at}mcgill.ca.

To the editor:

In their recent article, Legro et al. (1) claim to have studied urinary free cortisol (UFC) in adolescent females using "established RIA methods that employ methanol extraction before assay." They provide data for reproducibility (8%) and sensitivity (5 µg/24 h) and minimal data for cross-reactivity. No references are provided. It is not clear what the methanol extraction step consisted of or was meant to accomplish.

The assays used are presumably commercial RIAs, none of which has been shown to measure UFC accurately. Such assays are validated only for serum or plasma cortisol and give values that are much too high for UFC, as shown more than 20 yr ago and many times since when compared with data obtained after HPLC or other extensive chromatography (2), or more recently by liquid chromatography-tandem mass spectrometry (3). The values obtained by RIA are usually about three or more times higher than the true values, due to competition by large amounts of metabolites or other forms of interference. Although such RIA methods may have some clinical use in determining excessive cortisol production, they are unsuitable for physiological studies if one wishes to measure cortisol itself.

The nature of the interference has been poorly documented, so that one would not know if the same substances are responsible for interference in different samples or using different antibodies. We are not told how many different antibodies were used, but each antibody has its own set of cross-reactivities, and no two are identical. This makes it impossible to interpret data such as those shown by Legro et al. (1). For example, changes in metabolism resulting in different competing metabolites and, thus, differences in the amount of interference would not be apparent.

Mean or median values in healthy female adults obtained after extensive chromatography are approximately 20 µg/24 h (range, ~3–43 µg/24 h), approximately one third of the mean and range (67 ± 44 SD µg/24 h) reported here. Thus, approximately two thirds of the material measured is not cortisol. It is, therefore, obviously incorrect to refer to the material measured as UFC and, therefore, impossible to interpret their data.

Received April 22, 2003.

References

  1. Legro RS, Lin HM, Demers LM, Lloyd T 2003 Urinary free cortisol increases in adolescent Caucasian females during perimenarche. J Clin Endocrinol Metab 88:215–219[Abstract/Free Full Text]
  2. Murphy BEP 2002 Urinary free cortisol determinations—what they measure. The Endocrinologist 12:143–150
  3. Taylor RL, Machacek F, Singh RJ 2002 Validation of a high-throughput liquid chromatography-tandem mass spectrometry method for urinary cortisol and cortisone. Clin Chem 48:1511–1519[Abstract/Free Full Text]




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