Interpretation

Current guidelines recommend measurement of thyroglobulin (Tg) using a sensitive immunoassay (limit of quantification less than 1 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 anti-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 the apparent Tg concentration is below 1.0 ng/mL, the sample should be remeasured by liquid chromatography tandem mass spectrometry (LC-MS/MS). This will allow confident 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 work-up may 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, 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 has not yet passed 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 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, some specimens containing TgAb, which are negative for Tg by immunoassay, tested positive by LC-MS/MS. Therefore, measuring of Tg by LC-MS/MS is the preferred method in TgAb positive patients. The listed decision levels are for thyroid cancer follow-up of athyrotic patients and apply to unstimulated and stimulated thyroglobulin measurements. Decision levels are based on best practice guidelines and the literature, which includes Mayo Clinic studies.

Decision levels have not been established but are likely to be somewhat higher for thyroid cancer patients who are not completely athyrotic (ie, patient has some remnant normal thyroid tissue); remnant normal thyroid tissue contributes to serum Tg concentrations 0.2 to 1.0 ng/mL per gram of remnant tissue, depending on the thyrotropin (TSH) level.

Thyroglobulin by Mass Spectrometry:

Tg <0.2 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Undetectable Tg levels in athyrotic individuals on suppression therapy indicate a minimal risk (<1%-2%) of clinically detectable recurrent papillary/follicular thyroid cancer.

Tg ≥0.2 ng/mL to 2.0 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels of 0.2-2.0 ng/mL in athyrotic individuals on suppressive therapy indicate a low risk of clinically detectable recurrent papillary/follicular thyroid cancer.

Tg 2.1 ng/mL to 9.9 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels of 2.1-9.9 ng/mL in athyrotic individuals on suppression therapy indicate an increased risk of clinically detectable recurrent papillary/follicular thyroid cancer.

Tg ≥10 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels of 10 ng/mL or above in athyrotic individuals on suppressive therapy indicate a significant (>25%) risk of clinically detectable recurrent papillary/follicular thyroid cancer.

Thyroglobulin by Immunoassay:

Tg <0.1 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels below 0.1 ng/mL in athyrotic individuals on suppressive therapy indicate a minimal risk (<1%-2%) of clinically detectable recurrent papillary/follicular thyroid cancer.

Tg ≥0.1 to 2.0 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels 0.1 to 2.0 ng/mL in athyrotic individuals on suppressive therapy indicate a low risk of clinically detectable recurrent papillary/follicular thyroid cancer.

Tg 2.1 ng/mL to 9.9 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels 2.1 to 9.9 ng/mL in athyrotic individuals on suppressive therapy indicate an increased risk of clinically detectable recurrent papillary/follicular thyroid cancer.

Tg ≥10 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels 10 ng/mL or above in athyrotic individuals on suppressive therapy indicate a significant risk (>25%) of clinically detectable recurrent papillary/follicular thyroid cancer.