Spurious hypercalcitoninemia and heterophilic antibodies in patients with thyroid nodules

The purpose of our study was to examine the prevalence of significant heterophilic antibody (HAb) interferences in serum calcitonin measurement in a large cohort of patients with thyroid nodules.

Enrolled in the study were 378 patients with thyroid nodules shown not to have medullary thyroid carcinoma (MTC) after extensive diagnostic workup. Serum calcitonin measurement was performed before and after incubating each serum sample in heterophilic-blocking tubes (HBTs) and the differences were calculated. Samples showing an absolute percentage difference greater than 3 SD from the mean percentage difference were considered as affected by heterophilic antibody interference.

Five of 378 patients (1.3%) with HAb interferences were identified, 4 with clinically relevant false-positive calcitonin results.

A false-positive calcitonin result due to HAb interference occurs more frequently than MTC (1.3% vs 0%) in our patient series. A serum pretreatment in HBTs should be considered when increased serum calcitonin levels are found in a patient with a thyroid nodule to prevent unwarranted investigations or therapies.