Concordance between thyroglobulin antibody assays
Damon Parkington, Sonia Littleboy, Kevin Taylor, Sarah Jeffries, Helen Simpson & David Halsall
As thyroglobulin antibodies (TgAb) are a well recognised cause of interference in thyroglobulin (Tg) immunoassays current guidelines recommend that TgAb should be measured concurrently with Tg when monitoring thyroidectomised thyroid cancer patients. However the concordance between different TgAb assays has been questioned despite the availability of an International TgAb Reference Preparation (MRC 65/93).
Four commonly used TgAb assays were tested in 145 patients attending the Addenbrookes Thyroid Cancer Clinic. This included 44 patients with TgAb above and 112 patients below the manufacturers reference limits (<35 U/ml) using the DELFIA assay (PerkinElmer, Turku Finland). All samples were run using assays provided by BRAHMS (Hennigsdorf, Germany), Siemens Centaur (CA, USA) and Siemens Immulite. Recovery of exogenous Tg was ascertained for each patient using the Brahms Tg-plus immunoradiometric assay.
Results from the TgAb methods showed highly significant variance using the Freidman Rank test (P<0.0001). Seventeen patients were positive and 90 were negative for TgAbs by all four assays using criteria provided by the assay providers (40 U/ml for the Immulite, 60 U/ml for the centaur and 100 U/ml for the BRAHMS; concordance 74%). Twenty-two patients were positive by one assay alone, eight by two assays and eight by three assays.
Overall concordance could be increased to 90% by adjusting cut-offs to 80 U/ml for the DELFIA, 40 U/ml for the Immulite 160 U/ml for the centaur and 120 U/ml for the BRAHMS. However in lieu of a gold standard Tg assay the effects of these adjustments on the ability to detect interference cannot be determined.
Fourteen patients showed <70% recovery of exogenous Tg. One patient did not have positive TgAb result (manufacturers cut-offs). However Tg recovery was >70% in seven patients with positive TgAb results by all four assays. Tg recovery is neither a specific or sensitive test for the presence of TgAbs.