A 22-year-old presents with a uterus corresponding to 20 weeks size at 14 weeks amenorrhoea, bilateral theca-lutein cysts, and a urine pregnancy test reported negative. Serum beta-hCG sent undiluted returns 45,000 mIU/mL. On serial tenfold dilution, the serum value reads 480,000 mIU/mL. What phenomenon explains the initially discrepant results?

• A Heterophile antibody interference causing false elevation
• B Hook effect of antigen excess in the sandwich immunoassay ✓
• C Cross-reactivity with luteinising hormone in the assay
• D High-dose saturation of renal hCG clearance producing assay interference

Explanation

With extremely high hCG concentrations, the sandwich assay's capture and detection antibodies become saturated separately, preventing sandwich formation and yielding a falsely low or negative result. This is the hook (prozone) effect, classically seen in complete molar pregnancy and choriocarcinoma. Serial dilution of the sample restores proportionality and reveals the true level. Heterophile antibodies cause falsely elevated rather than falsely negative results, LH cross-reactivity is negligible in pregnancy assays, and renal clearance does not interfere with the assay chemistry.

Reference: Williams Obstetrics, 26th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.