Assay interference leading to misdiagnosis of central precocious puberty

Immunoassays are widely used to determine hormone levels. Antibodies directed against components of the immunoassay system can interfere with analyte concentration estimates. When unrecognized by clinicians, inappropriate clinical intervention may follow. The case of a young child with premature thelarche and elevated basal and stimulated luteinizing hormone (LH) levels is presented, in whom it is hypothesized that heterophile antibodies (HAs) caused interference in the LH immunoassay. LH concentrations were measured in two different assays: LH-microparticle enzyme immunoassay (MEIA) and LH-immunochemiluminometric assay (ICMA). To detect HA interference, LH level was remeasured after both preincubation with mouse serum to neutralize human anti-mouse antibodies, and treatment with a heterophile-blocking tube. The mean basal LH concentration by LH-MEIA was 7.4 mIU/mL and for LH-ICMA was 0.08 mIU/mL (normal range for age: 0.02-0.3 mIU/mL). LH concentration by MEIA was 0.08 mIU/mL after preincubation with mouse serum and 2.7 mIU/mL after preincubation with a heterophile blocking tube. In conclusion, HAs were identified in the serum of a child with premature thelarche. The presence of HAs led to spuriously elevated basal and gonadotropin-releasing hormone-stimulated LH concentrations, resulting in a diagnosis of central precocious puberty and unnecessary therapy. To avoid similar cases in the future, clinicians should consider the possibility of assay interference when the clinical picture is incongruent with the laboratory data.