Falsely elevated serum estradiol in woman of reproductive age led to unnecessary intervention and delayed fertility opportunity: a case report and literature review

Abstract

Background The optimal management of patients in reproductive endocrinology relies on the accuracy and validity of sex hormone assays. Endogenous or exogenous substances can compete with the analyte. This competition can result in interfering errors and falsely indicate elevated serum levels. Obvious interference in estradiol assays appears to occur rarely. Consequently, clinicians who are not familiar with the potential of interference could be misled. In addition to unnecessary investigations and interventions and severe mental stress, falsely elevated estradiol results can result in missed or delayed fertility opportunities. Case A 28-year-old female with pregnancy demand was diagnosed with polycystic ovary syndrome, Hashimoto’s thyroiditis and subclinical hypothyroidism. She was found to have persistently elevated levels of serum estradiol in the early follicular phase (between 527 and 642 pg/mL). Screening workup was performed for nearly 11 months to find the causes. Serum tumor biomarkers were normal. Abdominal and pelvic computed tomography were negative for adrenal or adnexal masses. A left mesosalpinx cyst and benign pathological results were achieved by laparoscopic surgery. Hormonal substances and dietary supplements were absent, as determined by dietary records. Ultrasound confirmed follicles could grow slowly and eventually ovulate. Falsely elevated estradiol levels were suspected due to the discrepancy among high estradiol levels, follicle growth and normal gonadotropin levels. Immunological interference by heterophile antibody was finally verified by two competitive chemiluminescent immunoassay platforms (estradiol levels in the early follicle phase: 619 pg/mL, Siemens ADVIA CENTAUR and 60 pg/mL, Beckman, DxI 800). Successful clinical pregnancy was eventually achieved by combining induced ovulation, ultrasound monitoring and intercourse guidance. Conclusions Analytical interference and laboratory error should be suspicious at first when the clinical characteristics contradict the laboratory results of serum hormones. Measuring serum estradiol with another immunoassay platform is an easy and non-time-consuming method to exclude the heterophile interfering.

Endogenous estrogen metabolites as oxidative stress mediators and endometrial cancer biomarkers

“…The optimal management of patients is contingent upon the accuracy and validity of E2 metabolite assays; therefore, clinicians must consider analytic interference and the fact that the laboratory’s accuracy is not reliable. False elevation of the serum E2 concentration due to analytical interference is uncommon and is typically associated with cross-reactive substances, such as the aromatase inhibitor exemestane and the selective ER degrader fulvestrant [ 56 ]. Falsely elevated levels of a supposed biomarker can lead to needless investigations and interventions, as well as severe mental stress.…”

Clinical utility of laboratory developed mass spectrometry assays for steroid hormone testing

“…Another report revealed that anti-bovine alkaline phosphatase antibodies in a patient sample interfered with an immunoassay measurement that utilizes bovine alkaline phosphatase in the assay reagent for amplification [ 48 ]. Additionally, a third report described a patient whose persistently elevated estradiol concentration measured by immunoassay led to an oncology work-up for a granulosa cell tumor of the ovary, including laparoscopy surgery and considerable stress to the patient [ 49 ]. After benign pathology results were reported, the clinicians suspected a false elevation and used a different immunoassay, which gave estradiol concentrations within the normal reference interval.…”

“…After benign pathology results were reported, the clinicians suspected a false elevation and used a different immunoassay, which gave estradiol concentrations within the normal reference interval. While no specific cause for the falsely elevated estradiol concentrations with the initial immunoassay was determined, it was postulated to be a heterophile antibody [ 49 ]. LC-MS/MS assays, on the other hand, can provide accurate results in the presence of heterophile antibodies, as they do not affect quantification by this methodology.…”