Undetectable Serum Thyroglobulin in Patients With Differentiated Thyroid Cancer: Antithyroglobulin Antibodies, Assay Limitation, or Other?

OBJECTIVE

To determine why some patients with differentiated thyroid cancer (DTC) lymph node (LN) metastases do not have detectable serum thyroglobulin (Tg).

METHODS

Fine needle aspiration biopsy (FNAB) washout fluid from patients with DTC LN metastases and undetectable serum Tg measurement by immunoassay (Tg-IA) were evaluated for the presence of Tg and anti-Tg antibodies (TgAbs). Spike-recovery experiments in serum were performed to assess the reason for undetectable Tg.

RESULTS

Of the 42 patients, 87% had detectable Tg in the FNAB washout fluid by Tg-IA, and 83% by Tg mass spectrometry (Tg-MS) measurement. Seventy-six percent of these patients had detectable serum TgAb, while 26% did not. Tg spike-recovery experiments performed on the TgAb+ (positive) serum samples showed decreased Tg recovery by Tg-IA but not by Tg-MS (Tg-IA mean, range: 50%, 12%-84%; Tg-MS 96%, 70%-117%). In TgAb- (negative) serum samples no interference was observed (>94% recoveries). No difference in FNAB washout fluid Tg recovery between TgAb- and TgAb+ patients was observed.

CONCLUSION

Tg was detected by both Tg-IA and Tg-MS methods in the majority of FNAB washout fluid from patients with DTC LN metastases who exhibited undetectable serum Tg by Tg-IA and Tg-MS. The absence of serum Tg could not be completely explained by the presence of TgAb. These results suggest that, for a subset of patients with DTC LN metastases, the absence of detectable Tg in serum does not appear to be due to analytical limitations of current Tg assays or the presence of TgAb interference.