Elevated estradiol in a prepubertal female: within-laboratory systematic and practical interference screening

Analytical errors related to endogenous or exogenous substances are a cause of unnecessary investigation, intervention, and patient concern especially in immunoassay platforms. In this report, we systematically screened for estradiol interference using a practical algorithm. For extended research in interference screening, repeated estradiol measurements for control and case samples were carried out for method comparison (three immunoassay platforms and one liquid chromatography-mass spectrometry (LC-MS/MS) measurement), dilution test, polyethylene glycol (PEG) precipitation, and heterophile antibody blocking tube. When serial dilutions were applied to the sample, a deviation from linearity was observed when compared to the control sample. With PEG precipitation, the recovery rate of 63%. While the patient's serum estradiol value was 389.02 pmol/L using the Siemens Atellica immunoassay method, the same sample was <36.7 pmol/L in the Abbott immunoassay method and 34.9 pmol/L in the Roche immunoassay platform. Applying the LC-MS/MS method, the patient had a serum estradiol of 3.33 pmol/L. Immunoassays are susceptible to interferences that can cause high estimates due to cross-reactivity. Therefore, LC-MS/MS may be more suitable than immunoassays for preventing misdiagnosis and inappropriate treatments, especially for children.