The first single-center randomized controlled trial, including 72 patients with DTC pretreated with recombinant human thyrotropin, Pilli and colleagues observed that short-term remnant ablation rates were the same (88.9 %) after administering 50 mCi, compared with 100 mCi of RAI (Pilli et al. 2007). Finally, two large high-powered multicentre national randomized trials conducted from France and from the UK independently proved noninferiority of Thyrogen stimulated RRA compared to T4 withdrawal RRA with 30 mCi or 100 mCi¹³¹I administration (Schlumberger et al. 2012; Mallick et al. 2012).

RECOMMENDATION 36 states that the minimum activity (30–100 mCi) necessary to achieve successful remnant ablation should be utilized, particularly for low-risk patients. (Recommendation rating: B). Now the time has come for all international guideline committees to revise the recommendations for remnant ablation. The new recommendation should advocate for 30 mCi of ¹³¹I for remnant ablation either under rhTSH stimulation or by THW.

There are several advantages to both the patient and healthcare provider for using a lower activity of radioiodine, including less time in isolation, a shorter hospital stay (when local or national regulations deem this necessary), reduced exposure of radioiodine to the environment, and lower financial cost. Furthermore, radioiodine ablation is associated with an increased risk of second primary malignancies; the lower the activity administered the lower the risk. The risks of radioiodine therapy must be considered. A large multicenter cohort study analyzed the risk of secondary malignancies in 6,841 patients with DTC (62 % were treated with radioiodine) (Rubino et al. 2003). The investigators observed a significant 30 % increased risk of second primary malignancies in patients treated with radioiodine, and there appeared to be a linear relationship between the cumulative dose and solid tumors (4 % increased risk/GBq¹³¹I). An estimated 53 solid tumors are expected among 10,000 patients after 10 years if they were treated with 100 mCi compared with only 16 if they had been treated with 30 mCi. Although these data are estimates from an extrapolation of higher cumulative doses of radioiodine, and not actual data from patients receiving 100 mCi ¹³¹I, they should provoke thyroidologists to consider that there may be risks—however small it may be associated with administration of radioiodine for remnant ablation (Iyer et al. 2011; Sawka et al. 2009).

A prospective cohort study (Jonklaas et al. 2006) of 2,936 patients found that OS improved significantly when the TSH was suppressed to undetectable levels in patients with National Thyroid Cancer Treatment Cooperative Study Group (NTCTCSG) stage III or IV disease and suppressed to the subnormal to undetectable range in patients with NTCTCSG stage II disease; however, in the latter group there was no incremental benefit from suppressing TSH to undetectable levels. Suppression of TSH was not beneficial in patients with stage I disease. In another study, there was a positive association between serum TSH levels and the risk for recurrent disease and cancer-related mortality (Hovens et al. 2007; Brabant 2008).

ATA RECOMMENDATION 40 states that initial TSH suppression to below 0.1 mU/L is recommended for high-risk and intermediate-risk thyroid cancer patients, while maintenance of the TSH at or slightly below the lower limit of normal (0.1–0.5 mU/L) are appropriate for low-risk patients. Similar recommendations apply to low-risk patients who have not undergone remnant ablation, i.e., serum TSH 0.1–0.5 mU/L. (Recommendation rating: B)

The benefit of radioiodine in younger patients with smaller tumors (≤4 cm) is less clear, and potential risks of therapy need to be thoroughly considered. We must individualize radioiodine therapy-(a) use 30 mCi ¹³¹I for RRA either with rhTSH stimulation or THW, the lowest effective dose of radioiodine, in low-risk patients; (b) for older patients with larger tumors (>4 cm), and patients with lymph node involvement, may significantly benefit from RRA, probably with higher dose of radioiodine (≥50 mCi). The current reality is that in the absence of randomized clinical trial to prove or disprove the beneficial long-term effect of RRA, the decision-making about RRA in low-risk thyroid carcinoma is difficult and complex. Thus, till definite evidence is generated from high quality future study, one must limit the known harmful effect of radiation, and the good clinical practice must follow the basic principle of primum non nocere (Latin phrase that means “first, do no harm”).