Falsely elevated FSH levels due to assay interference: a case-based approach.

Laboratory results are important to patient diagnosis and management. Immunoassay interference can lead to misleading results and inappropriate clinical decisions. We present the case of a 30-year-old woman with secondary amenorrhea and unexpectedly elevated follicle-stimulating hormone (FSH) levels that did not align with her clinical findings, including normal ovarian reserve and spontaneous return of menstruation. Suspecting assay interference, a comprehensive evaluation was undertaken, including serial dilution, polyethylene glycol (PEG) precipitation, heterophile antibody blocking, and method comparison studies. Non-linear serial dilution results and markedly low FSH recovery after PEG precipitation (7.09 %) supported the presence of macro-FSH or interfering antibodies. Heterophile blocking tube tests showed no significant effect, making heterophile interference less likely. However, method comparison revealed discordant FSH values across platforms, with only Advia Centaur XP reporting within the reference range. Notably, Advia Centaur used sheep-derived detecting antibodies, unlike Abott Architect i 2000 and Roche Elecsys, which both used mouse-derived antibodies. This led to the hypothesis of an autoantibody against mouse-derived detecting antibodies as the source of interference. This case underscores the importance of close collaboration between clinicians and laboratory professionals to identify assay interference, ensuring accurate diagnosis and avoiding unnecessary interventions.