Heterophile antibodies may cause falsely lowered serum cortisol values

Abstract

This report demonstrates that potentially significant consequences can arise from the failure to consider heterophile antibody interference. Clinicians who interpret test results need to be aware of the potential for interference in immunoassays by heterophile antibodies.

Cosyntropin-stimulated salivary cortisol in hospitalized patients with hypoproteinemia

“…Estrogen-containing medications and highestrogen conditions (such as pregnancy) result in high CBG concentrations, which will elevate serum total cortisol concentration without truly representing an increased serum free cortisol level [6,23]. Heterophile antibodies present in the serum can interfere with serum total cortisol immunoassay testing and result in false low measurement values [25].…”

When laboratory tests can mislead even when they appear plausible

“…A more realistic general 'guestimate' in practice would be 0.4-1%, which is still high; hence the need for awareness and caution. [1][2][3][4][5][6][7][8][9] Probabilistic reasoning based on Bayesian inference, which takes into account key relevant information such as the rate of analytical inherent error and disease prevalence/incidence, is a concept that can help in identifying potentially false results and quantifying the likelihood of false positive and negative data.…”

“…10,11 The immunoassay used to measure TSH may be assumed to have an excellent diagnostic accuracy of 99.6% and an error rate of ±0.4% (considered among the lowest reported). [1][2][3][4][5][6][7][8][9] This means four false positives or negatives are predicted per thousand in any population sample.…”

“…Unquestioning acceptance at face value may lead to misdiagnosis and mistreatment or unnecessary surgery for unconfirmed disease with consequent iatrogenic morbidity. [1][2][3][4][5][6][7][8][9] A probabilistic rationale based on Bayes' theorem 1 -in which key information, such as (a) the rate of inherent analytical error in a test and (b) the disease prevalence (number of cases per head of ABSTRACT When laboratory tests can mislead even when they appear plausible population) or incidence (rate of new cases over a period of time), is taken into account -can be used to evaluate the likelihood of an erroneous result occurring and its nature, ie false positive or false negative. Essentially, in disorders with low prevalence/incidence and/or when a test is used as a screen with vague or insufficient clinical correlates, erroneous results are likely to be false positives.…”

“…5 The case fatality rate (CFR) for this epidemic was estimated to be between 31% and 74% in the three most affected countries in West Africa, with an average CFR of 48% for hospitalised patients; this is largely consistent with the range of CFRs reported for previous Ebola Zaire (EBOV) outbreaks. [6][7][8][9][10][11] Cases were also diagnosed in Senegal, Nigeria, Mali, USA, UK, Italy and Spain. Evacuated cases were treated in France, Italy, the Netherlands, Switzerland, Norway, Germany, the USA and the UK.…”