Interpretation

Current guidelines recommend measurement of thyroglobulin (Tg) with a sensitive immunoassay (limit of quantification <1.0 ng/mL); for measurements of unstimulated Tg, the detection limit should be in the 0.1 to 0.2 ng/mL range.

In all cases, serum thyroglobulin autoantibodies (TgAb) should also be measured, preferably with a method that allows detection of low concentrations of TgAb. If TgAb are detected, the laboratory report should alert the ordering provider to the possibility of falsely low Tg results if using an immunometric assay. If the apparent Tg concentration is below 1.0 ng/mL, the sample should be remeasured by mass spectrometry. This will allow accurate detection of Tg, in the presence of TgAb, down to 0.2 ng/mL (risk of residual/recurrent disease <1%-3%).

Samples from patients with Tg concentrations above 1.0 ng/mL might not require Tg measurement by mass spectrometry because current guidelines suggest further workup might be necessary above this threshold. However, the positive predictive value for residual/recurrent disease is modest when Tg is just above this threshold (3%-25%) in athyrotic patients. Above 10 ng/mL, the risk of residual/recurrent disease is at least 25%, with many studies showing 60% to above 90% risks. In selected patients, therefore, it might also be useful to test TgAb positive samples by mass spectrometry, even if the Tg concentration is above 1.0 ng/mL but not above the 10 ng/mL threshold. These considerations are even more relevant in patients with a known thyroid remnant of a few grams, who may always have serum Tg concentrations of 1.0 to 10 ng/mL, owing to remnant Tg secretion, regardless of the presence or absence of residual/recurrent cancer.

It has been determined that the presence of antithyroglobulin autoantibodies (TgAb) in serum can lead to underestimation of Tg concentration by immunometric methods. When TgAb are present in samples with detectable Tg, the Tg values may be underestimated by up to 60% in immunoassays. In addition, approximately 20% of specimens containing TgAb, which are negative for Tg by immunoassay, tested positive by liquid chromatography tandem mass spectrometry. Therefore, measuring Tg by mass spectrometry is the preferred method in TgAb positive patients.

Thyroglobulin reference intervals are for patients with an intact thyroid and not for patients who have had surgery for thyroid cancer. Tg reference intervals in patients that have undergone thyroidectomy or any treatment for follicular thyroid cancer are dependent on the residual mass of the thyroid tissue after surgery. Tg results, regardless of concentration, should not be interpreted as absolute evidence for the presence or absence of papillary or follicular thyroid cancer. This result needs to be interpreted in the context of the clinical evaluation.