Discordant serum thyroglobulin results generated by two classes of assay in patients with thyroid carcinoma: correlation with clinical outcome after 3 years of follow-up

Background: Serum thyroglobulin measurement is an integral part of monitoring patients with thyroid carcinoma, but analytic problems pose serious difficulties in the utility of this test.

Methods: Between 1997 and 1998, serum samples from 83 patients with differentiated thyroid carcinoma were collected. Serum thyroglobulin was assayed by both radioimmunoassay and by an immunoradiometric assay. The disease status of patients with discordant serum thyroglobulin results was assessed in June 2001. Therefore, the predictive value of a single thyroglobulin measurement was assessed by evaluating the clinical status of patients 3 years later.

Results: Discordant serum thyroglobulin results were noted in 17 (20.4%) patients. Of the 17 patients with discordant results, 16 had adequate clinical follow-up data. Of these 16 patients, 11 patients had detectable levels of serum thyroglobulin by immunoradiometric assay (range, 1.4-350 microg/L) whereas levels were undetectable by radioimmunoassay (< 1 microg/L). All 11 patients had evidence of metastases 3 years later. Two patients had undetectable serum thyroglobulin levels using the immunoradiometric assay (< 1 microg/L), whereas they had detectable levels using radioimmunoassay (serum thyroglobulin 7.2-30 microg/L). The serum samples from both patients had normal recoveries and positive antithyroglobulin antibodies. Both patients developed metastases 3 years later.

Conclusions: False-negative serum thyroglobulin results were significantly higher with the radioimmunoassay method compared with the immunoradiometric assay. The immunoradiometric assay is more reliable than the radioimmunoassay, particularly in patients who have no thyroglobulin antibodies. This finding is novel in that traditional immunoradiometric assay systems compared with radioimmunoassays usually have a higher incidence of false-negative results when assessed against clinical status. The immunoradiometric assay is subject to false-negative results in some patients with thyroglobulin antibodies, even when recovery experiments indicate the absence of interference. Thyroglobulin antibodies should be measured in all patients with differentiated thyroid carcinoma and if positive, results should be interpreted with extreme caution.