Traditionally, oestradiol measurement is performed by immunoassay. The sensitivity of these assays is not sufficiently sensitive for certain patient groups such as males, post-menopausal females and children. There is also a potential for interference from structurally related compounds or heterophilic antibodies. LCMS/MS is an attractive alternative as it has increased sensitivity and specificity.
We reviewed the requests for LCMS/MS analysis during the first 6 months of its availability. During this period 20% of samples were sent for specific LCMS/MS analysis due to suspected immunoassay interference. Of these, three samples also gave raised oestradiol concentrations using LCMS/MS. One sample with undetectable oestradiol was from a breast cancer patient who had undergone an oopherectomy as the oestradiol concentration was detectable by immunoassay. Because it remained detectable after oopherectomy, the sample was referred for LCMS/MS analysis which identified interference in the immunoassay. Another sample was on a child who was being considered to have an oestradiol secreting tumour based on immunoassay results. Upon analysis using LCMS/MS, oestradiol were undetectable, thus preventing any further investigation.
The remaining 80% of samples were from breast cancer patients. There are reports in the literature of treatments for breast cancer causing interference in immunoassays. We performed spiking experiments of common treatments for breast cancer: tamoxifen, anastrozole, exemestane and fulvestrant and measured the samples by immunoassay and LCMS/MS. Fulvestrant was the only drug found to cause interference in the immunoassays, however the potential for metabolite interference for the other drugs remains.
We have shown several cases where the availability of this LCMS/MS assay for oestradiol has had a direct impact on the quality of patient care and has proven to fill gaps previously not covered by immunoassay. This assay is available in an accredited NHS laboratory to make it accessible for all clinicians and their patients in the UK.