Influence of Thyroglobulin Autoantibodies on Thyroglobulin Levels Measured by Different Methodologies: IMA, LC-MS/MS, and RIA

Context Serum thyroglobulin (Tg) measured by immunometric assay (IMA) is prone to underestimation due to Tg autoantibody (TgAb) interference, often prompting reflex Tg measurement by liquid chromatography/tandem mass spectrometry (MS) or radioimmunoassay (RIA). Objective IMA, MS, and RIA methodologies were used to measure serum Tg in TgAb-negative (TgAb-) and TgAb-positive (TgAb+) patients with either distant metastatic differentiated thyroid cancer (DTC) or hyperthyroidism (HY)-patients in whom a detectable serum Tg would be expected. Results When TgAb was absent, all methodologies detected Tg in the sera of all DTC and HY patients and reported appropriate Tg trends and treatment responses for DTC patients with progressive distant metastatic disease, albeit with high between-method variability (> 30% coefficient of variability). When TgAb was present, all methodologies reported lower serum Tg levels for both DTC and HY groups vs their respective TgAb- group. No Tg was detected by IMA or MS in similar to 50% TgAb+ DTC patients (6% had no Tg detected by RIA). Surprisingly, 5% of TgAb+ HY patients also had no Tg detected by IMA or MS. The inverse log TgAb/log Tg correlations seen for the TgAb+ HY patient group with all methods suggested the presence of a TgAb-associated serum Tg-lowering effect. Conclusion (i) Between-method Tg variability necessitates method continuity when monitoring the Tg trends of TgAb- DTC patients. (ii) The presence and concentration of TgAb appeared to have a lowering effect on serum Tg measured by all methodologies (IMA, MS, and RIA). (iii) Since the reliability of Tg measured in the presence of TgAb is often uncertain, the TgAb trend (measured by the same method) may be a useful surrogate DTC tumor marker.