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

Area of Science:

• Clinical Chemistry
• Endocrinology
• Laboratory Medicine

Background:

• Laboratory results are critical for patient diagnosis and management.
• Immunoassay interference can lead to erroneous results and clinical decisions.
• Accurate hormone level measurement is essential for reproductive health assessment.

Observation:

• A 30-year-old woman presented with secondary amenorrhea and unexpectedly high follicle-stimulating hormone (FSH) levels.
• Her clinical presentation, including normal ovarian reserve and spontaneous menstruation, contradicted the elevated FSH.
• Initial investigations suggested immunoassay interference rather than a true endocrine disorder.

Findings:

• Serial dilution and polyethylene glycol (PEG) precipitation indicated the presence of macro-FSH or interfering antibodies.
• Heterophile antibody blocking tests were inconclusive.
• Method comparison revealed significant discrepancies in FSH levels across different immunoassay platforms.
• The Advia Centaur XP, using sheep-derived antibodies, reported normal FSH, while platforms using mouse-derived antibodies showed interference.
• This suggested an autoantibody against mouse-derived detecting antibodies as the likely cause.

Implications:

• Accurate immunoassay testing is crucial for correct patient diagnosis and treatment.
• Assay interference can lead to misdiagnosis and unnecessary interventions.
• Close collaboration between clinicians and laboratory professionals is vital for identifying and resolving immunoassay interferences.
• Understanding antibody specificities in different assay platforms can aid in troubleshooting discordant results.