Indication for Radioactive Iodine in Patients With Papillary Thyroid Carcinoma Without Apparent Disease After Total Thyroidectomy But With Elevated Antithyroglobulin Antibodies

Fátima Ramos da Silva; Pedro W. Rosario; Gabriela F. Mourão


Clin Endocrinol. 2022;96(1):82-88. 

In This Article

Abstract and Introduction


Objective: To evaluate a criterion for the selective indication of radioactive iodine (RAI) based on the short-term behaviour of antithyroglobulin antibodies (TgAb) in patients with papillary thyroid carcinoma (PTC) who have negative thyroglobulin (Tg) and neck ultrasonography (US) without abnormalities after total thyroidectomy but elevated TgAb.

Design: This was a prospective study that evaluated 216 patients with low- or intermediate-risk PTC who had nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities but elevated TgAb 3 months after thyroidectomy. RAI was not indicated in patients with negative TgAb or a >50% reduction in TgAb concentrations 6 months after initial assessment followed by a negative test or an additional reduction (also >50%) after 12 months.

Results: Only two of the 114 patients who did not receive RAI developed recurrences; another 108 patients met the criterion of an excellent response to therapy in the last assessment and TgAb persisted in four patients but there was an additional reduction in their concentration during follow-up. Among the 102 patients who received RAI, post-therapy whole-body scanning (RxWBS) detected persistent disease in 8 (8%). Two of the 94 patients without persistent disease on RxWBS developed recurrences. In the last assessment, in the absence of additional treatment, 54/92 patients (58.7%) without structural recurrence had negative TgAb.

Conclusions: The indication for RAI can be based on the short-term behaviour of TgAb in patients with PTC and elevated TgAb after thyroidectomy who are not high risk and who do not have apparent disease (nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities).


After total thyroidectomy and administration of radioactive iodine (RAI) in patients with papillary thyroid carcinoma (PTC), complete ablation or an excellent response to therapy is defined when (i) nonstimulated thyroglobulin (Tg) < 0.2 ng/ml or stimulated Tg < 1 ng/ml, (ii) antithyroglobulin antibodies (TgAb) are negative and (iii) neck ultrasonography (US) shows no abnormalities.[1,2] In the case of low-risk and even intermediate-risk patients who achieve these results after surgery, post-therapy whole-body scanning (RxWBS) rarely reveals persistent disease,[3–7] and the risk of recurrence is low even if they do not receive RAI.[8–13] The combination of the cited postoperative findings (i–iii) has, therefore, been recommended by many authors as a parameter to exempt patients from RAI therapy.[1,3–15]

Circulating TgAb interfere with serum Tg, almost always underestimating the concentrations of the latter.[16] Thus, the studies reporting an excellent negative predictive value of postoperative Tg excluded patients with TgAb.[3–13] In the presence of circulating TgAb, even if Tg is undetectable and US shows no abnormalities, the response to therapy is considered indeterminate or incomplete.[2] If this applies to patients who had already received RAI and whose RxWBS was known to be negative,[2] the concern is greater for those who have not yet received RAI and for whom RxWBS has not been obtained. Specifically in patients with TgAb after thyroidectomy and before ablation, Nabhan et al.[17] found metastases on RxWBS in 15%, although the patients were low risk (T1–2cN0); Dekker et al.[18] diagnosed structural disease up to 1 year after RAI also in 15% of patients; Schlumberger et al.[7] showed that the frequency of persistent structural disease was similar to that observed in patients with stimulated Tg ≥ 10 ng/ml; Zhang et al.[19] reported the persistence of uptake on DxWBS or structural recurrence in one-third of the patients and Trimboli et al.[20] observed 20% of recurrences and 5% of disease-related deaths despite initial therapy with RAI. Finally, a meta-analysis demonstrated a 2.8 times higher risk of persistent/recurrent disease in patients with TgAb.[21] Currently, the recommendation of exempting patients from RAI based on Tg and the postoperative US does not apply to patients with TgAb. On the contrary, some authors recommend the administration of RAI to patients with TgAb after thyroidectomy.[4,14,15,22–24] It should be noted that up to 25% of patients with PTC may exhibit TgAb during postoperative assessment.[8,16,18,20,25]

A criterion for the selective indication of RAI in patients with TgAb after thyroidectomy is very desirable. The behaviour of TgAb is a known predictor of recurrence risk in patients treated with RAI.[16,20,26–29] However, no studies have evaluated the short-term behaviour of TgAb after total thyroidectomy as a parameter for the indication of RAI.

The objective of this prospective study was to evaluate a criterion for the selective indication of RAI based on the short-term behaviour of TgAb in patients with low- or intermediate-risk PTC who had negative Tg and US but elevated TgAb in the first assessment after total thyroidectomy. It should be noted that this is the first occasion for measurement of these markers as it is not recommended before surgery.[2,24]