Undetectable Thyroglobulin in Patients With Differentiated Thyroid Carcinoma and Residual Radioiodine Uptake on a Postablation Whole-Body Scan

Aim To assess the impact of laboratory interferences and pitfalls in producing falsely undetectable Tg in differentiated thyroid carcinoma (DTC) patients with residual iodine-avid thyroid tissue on a posttreatment whole-body scan (PT-WBS). Methods From 298 consecutive patients with histologically proven DTC, 47 patients (16%) with undetectable serum Tg but residual ¹³¹I uptake on a PT-WBS were selected. Interferences from antithyroglobulin antibodies (TgAb), heterophile antibodies, and hook-effects were screened; in the remaining samples, serum Tg was measured in 3 different immunoassays. Results Of 47 patients, 11 (23%) showed interference from either thyroglobulin antibodies (n = 10) or heterophile antibodies (n = 1). Among the 36 remaining patients, 18 showed detectable Tg levels after retesting using a different immunoassay, whereas the remaining 18 patients also showed detectable Tg levels in a third Tg immunoassay. However, only 7 patients showed a detectable Tg in both secondarily used assays. Tg levels remained undetectable in all methods in 9 patients (19%) even after extensive laboratory work-up and despite the presence of ¹³¹I-avid tissue found in PT-WBS. Conclusions A careful assessment of interferences in Tg measurement significantly reduced the occurrence of undetectable Tg among patients with ¹³¹I uptake in PT-WBS. However, such extensive assessment is difficult in clinical practice and one-fifth of patients still had undetectable Tg in multiple assays despite an intensive laboratory work-up. A benchmark between ¹³¹I imaging and Tg measurement authenticates the interpretation of Tg measurements and, consequently, remains of pivotal value by authenticating the use of serum Tg during further follow-up of DTC patients.