Thyroglobulin assay during thyroxine treatment in low-risk differentiated thyroid cancer management: comparison with recombinant human thyrotropin-stimulated assay and imaging procedures

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Abstract
Circulating human thyroglobulin (TG) measurement has a pivotal role in the management of patients affected by differentiated thyroid cancer (DTC). Undetectable thyrotropin (TSH)-stimulated serum TG after thyroid ablation (i.e., thyroidectomy and radioiodine) implies the absence of residual or relapsing DTC. Recently, high-cost recombinant human TSH (rhTSH) was proposed for TG stimulation to avoid uncomfortable thyroxine (T(4)) withdrawal. However, only a small fraction of relapsing DTC patients showed undetectable TG under T(4) treatment (onT(4)-TG) by high-sensitivity assays. The present study was undertaken to compare onT(4)-TG with the rhTSH-stimulated TG assay (rhTSH-TG), (131)I scanning and neck ultrasound (US) with fine-needle aspiration biopsy. We enrolled 117 patients with histologically proven DTC treated by total thyroidectomy and radioiodine. Inclusion criteria were: complete tumour excision, no radioiodine uptake outside of the thyroid bed at post-treatment scan and undetectable onT(4)-TG 3 months after primary treatment. At 1 year after radioiodine treatment, all patients underwent onT(4)-TG assay, rhTSH-stimulated TG assay, (131)I scanning and neck US. Based on histology, clinical data and long-term follow-up, persistent/relapsing disease was confirmed in 14 patients. onT(4)- and rhTSH-TG were positive in 10 and 12 patients, respectively and two patients converted from undetectable to detectable TG after rhTSH administration. Neck US was positive in 10 patients and a combination of US with onT(4)- and rhTSH-TG assays showed positivity in 13 and 14 out 14 patients, respectively. A radioiodine scan was positive in six patients, all with positive onT(4)- and rhTSH-TG levels. Globally, the negative predictive value of the onT(4)- and rhTSH-TG assays was 99% and 100%, respectively, and 104 rhTSH stimulations had to be performed to detect one local recurrence with negative onT(4)-TG. Our preliminary data need further confirmation on larger groups of patients, but seem to indicate that onT(4)-TG assay by a high-sensitivity method combined with neck US may avoid rhTSH stimulation in low-risk DTC patients after surgery and radioiodine thyroid ablation.

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