Heterophile Antibodies May Falsely Increase or Decrease Thyroglobulin Measurement in Patients with Differentiated Thyroid Carcinoma

Background: To examine the prevalence of significant interference from heterophile antibodies (HAb) in the measurement of serum thyroglobulin (Tg), we evaluated a large cohort of samples from patients with differentiated thyroid carcinoma (DTC).

Methods: Serum Tg measurements were performed in 406 serum samples before and after incubation of each serum sample in heterophile-blocking tubes (HBT) at room temperature for 1 h. We calculated the difference between the original Tg value and the value obtained after HBT treatment. We considered any sample showing an absolute percent difference >3 SD from the mean percent difference as being affected by HAb interference.

Results: We identified five patients (1%) as showing interference from HAb. Of these, three (60%) showed a false positive or falsely increased Tg concentration without any recurrence following clinical work-up; two (40%) showed a false negative or falsely reduced Tg levels, and metastases were detected in both cases by imaging procedures.

Conclusions: HAb may increase as well as reduce the measured Tg in a significant number of patients. A positive HAb interference should be suspected if Tg elevation does not fit the clinical pictures. A negative interference is a more challenging problem because increases in Tg generally occur as the first sign of recurrence of DTC. Therefore, treatment using HBT tubes of all sera referred for Tg measurement should be considered in order to prevent both unwarranted investigations or therapy, and delayed diagnosis of recurrence in patients affected by DTC.