Response to Yan et al. re: “Could Radioactive Iodine Be a Preferred Therapy for Graves' Hyperthyroidism Patients with Large Goiters? A Viewpoint from China”

Dear Editor:

The authors suggest in a letter to the editor ¹ that radioactive iodine (RAI) should be a preferred therapy for Graves' hyperthyroidism with large goiters. Table 5 of the 2016 American Thyroid Association (ATA) hyperthyroidism guidelines ² grade the options for treating Graves' hyperthyroidism as “preferred,” “acceptable,” or “not first line but may be acceptable depending on the clinical circumstances.” It is therefore important to clarify the author's concern. I assume that the authors are suggesting that RAI along with surgery should be graded as “preferred,” and not that RAI is preferred over surgery or antithyroid drugs.

However, there is no category of large goiter listed in Table 5. The associated text states that large goiter (≥80 g) “favors” surgery, but this does not preclude using RAI. The only closely relevant category is if the Graves' gland contains “large thyroid nodules, especially if >4 cm or if nonfunctioning or hypofunctioning on ¹²³I or ⁹⁹Tc pertechnetate scanning.” RAI was rated “not first line…” which I hope the authors find reasonable if there is a 4 cm nonfunctioning nodule within a Graves' gland?

Table 8 of the 2016 ATA guidelines applies to toxic nodular goiter and toxic adenoma, and the category of “large goiter/nodule” without or with “substernal or retrosternal extension” is graded as “preferred” for surgery and “acceptable” for RAI. Perhaps the authors disagree with these grades, but their letter indicates a concern specifically with Graves' disease. A recent study documented the acquired suspicious ultrasound characteristics of autonomous nodules that were previously treated with radioiodine, ³ an issue which many consider in choosing among the three treatment options for toxic adenoma/toxic multinodular goiter.

The authors correctly point out that large goiters, whether Graves' disease or toxic nodular goiter, frequently are undertreated with radioiodine, which likely contributes to treatment failure. However, the reasons for undertreatment are not always as simple as calculating volume and activity correctly. The correctly calculated activity for patients with large goiters may place patients at increased risk for radiation-related complications, including oncogenesis, especially breast cancer. ⁴ In many countries, patients may require a hospital admission or heightened radiation precautions if the calculated dose exceeds specific thresholds. Hence, the ATA guidelines suggest radioactive iodine uptake insufficient for RAI therapy as an indication for surgery over RAI.

Of note, patient acceptance of radioiodine as a treatment modality has fallen off dramatically in recent years. The use of radioiodine for hyperthyroidism reportedly fell 85% between 2006 and 2019 at the Massachusetts General Hospital, ⁵ presumably because of the increased risk of thyroid eye disease, as well as concerns of potential oncogenesis.

In short, the 2016 ATA guidelines favor surgery, but in no way preclude the use of radioiodine, for patients with Graves' disease and large goiters.