Spuriously elevated estradiol due to immunoassay interference in the workup of a suspected ovarian tumor: Diagnostic pitfalls and laboratory workflow recommendations

Background: Falsely elevated estradiol levels due to analytical interference are rare but clinically relevant diagnostic pitfalls, particularly when results suggest an estrogen-producing tumor. Case presentation: We report the case of a 51-year-old woman with markedly increased estradiol concentrations inconsistent with her clinical presentation and hormonal status. Persistently elevated estradiol values, together with imaging findings and concern for granulosa cell tumor, contributed to the diagnostic workup of a suspected estrogen-producing ovarian tumor. Bilateral salpingo-oophorectomy was performed within a multifactorial preoperative assessment; histopathology showed no evidence of malignancy. Laboratory investigation: Postoperatively, estradiol remained markedly elevated despite gonadotropin values consistent with surgical menopause. Re-measurement on an alternative immunoassay platform revealed low postmenopausal estradiol levels, whereas the original competitive chemiluminescent assay continued to show persistently elevated values. Polyethylene glycol precipitation produced a substantial reduction in estradiol concentration, supporting immunoglobulin-mediated analytical interference, most likely due to heterophile antibodies. Discussion: This case highlights the vulnerability of competitive immunoassays to analytical interference, which may paradoxically generate falsely elevated results through signal suppression. Clinical–biochemical discordance should prompt timely communication between clinicians and laboratory specialists, repeat testing, alternative-platform measurement, and targeted interference studies. Conclusion: Recognition of analytical interference is essential to prevent misdiagnosis and avoid unnecessary or potentially harmful interventions. We propose a practical diagnostic workflow to support the identification and management of discordant estradiol results in routine laboratory practice.