Background: Serum thyroglobulin is the marker of differentiated thyroid cancer after initial treatment and TSH stimulation increases its sensitivity for the diagnosis of recurrent disease.

Aim: To compare the diagnostic values of 7 methods for serum Tg measurement for detecting recurrent disease during both L-thyroxine (L-T4) treatment and following TSH stimulation.

Methods: Thyroid cancer patients who had no evidence of persistent disease following initial treatment (total thyroidectomy and radioiodine ablation) were studied at 3 months on LT4 treatment (Tg1) and then at 9-12 months following withdrawal or rhTSH stimulation (Tg2). Sera with anti-Tg antibodies or with an abnormal recovery test result were excluded from Tg analysis with the corresponding assay. The results of serum Tg determination were compared to the patient's clinical status at the end of follow-up.

Results: 30 recurrences were detected among 944 patients. A control ¹³¹I total body scan had a low sensitivity, a low specificity and a low clinical impact. Assuming a common cut-off for all Tg assays at 0.9 ng/mL, sensitivity ranged from 19-40% and 68-76% and specificity from 92-97% and 81-91% for Tg 1 and Tg2, respectively. Using assays with a functional sensitivity at 0.2-0.3ng/mL, sensitivity was 54-63% and specificity was 89% for Tg1. Using the 2 methods with a lowest functional sensitivity at 0.02 and 0.11ng/mL, resulted in a higher sensitivity for Tg1 (81% and 78%), but at the expense of a loss of specificity (42% and 63%); finally, for these two methods using an optimized functional sensitivity according to ROC curves at 0.22 and 0.27ng/mL resulted in a sensitivity at 65% and specificity at 85-87% for Tg1.

Conclusion: Using an assay with a lower functional sensitivity may give an earlier indication of the presence of Tg in the serum on L-T4 treatment and may be used to study the trend in serum Tg without performing any TSH stimulation.