Preoperative undetectable serum thyroglobulin in differentiated thyroid carcinoma: incidence, causes and management strategy

Background In recent years serum thyroglobulin (Tg) measurement during thyroxine (T4) treatment and/or after stimulation by endogenous TSH or recombinant human TSH (rhTSH) has eclipsed other diagnostic procedures in managing patients with differentiated thyroid cancer (DTC). However, preoperative undetectable Tg was reported in up to 12% of patients affected by DTC and recurrences of DTC with no increase in serum Tg have also been described. Clearly, a negative Tg measurement may falsely reassure both the patient and the clinician in these cases.

Aim We retrospectively evaluated the incidence of undetectable or reduced preoperative serum Tg in a group of 436 patients affected by DTC. Additionally, we evaluated the role of Tg retesting by two different immunoassays in patients with low Tg at first measurement.

Methods We retrospectively selected 17 patients with undetectable (i.e. less than functional sensitivity of assay method) or reduced Tg (i.e. between functional sensitivity and minimum normal value) among 436 patients with histologically proved DTC. The remaining 419 patients were used as control cases. Frozen sera from all patients were retested by two different Tg immunoassays.

Results Globally, 17 out of 436 (3·8%) patients showed undetectable (n = 5, 1·1%) or reduced (n = 12, 2·7%) preoperative Tg. The Tg level was above the minimum normal value in 3 and 4 out of 5, and 8 and 9 out of 12 of these patients, respectively, when two different immunoassays were employed. On the other hand, undetectable or reduced Tg levels were found in 3·0%–5·1% of control cases when different immunoassays were used.

Conclusions Regardless of the method employed, 3·0–5·1% of patients with DTC showed undetectable or reduced preoperative Tg. This fact must be recognized, as Tg cannot be used as a benchmark for DTC follow-up in these cases. However, Tg retesting with different immunoassays seems to be useful in ruling out these pitfalls in a large majority of patients, and also indicates the most effective assay to be employed in these cases.