Re: “Active Surveillance Outcomes of Patients with Low-Risk Papillary Thyroid Microcarcinoma According to Levothyroxine Treatment Status” by Yamamoto et al.

Dear Editor:

Active surveillance (AS) has been widely accepted as a management option for low-risk papillary thyroid microcarcinoma (PTMC), which has become a first-line recommendation in some guidelines. However, there are still some controversies.

A retrospective study published in Thyroid conducted by Yamamoto et al. indicated that levothyroxine (LT4) treatment might be associated with decreased tumor growth during AS of PTMC. ¹ After reading the article, we had some reflections.

First, the article suggested that some patients take LT4 for thyrotropin (TSH) suppression treatment during AS. However, there are no standards for LT4 administration for patients under AS without hypothyroidism. Potentially excessive intake of LT4 might increase the risk of several side effects, including (a) cardiovascular problems, such as cardiac arrhythmias and heart failure. (b) osteoporosis and risk of skeletal fractures in postmenopausal women, and (c) loss of muscle function and psychological instability. ² Patients may also suffer from fatigue and cognitive impairment, which may result in poor quality of life. In addition, excessive LT4 treatment has been related to gestational hypertension, preeclampsia, and preterm birth. ² All these potential problems seem to be more severe than PTMC. We wonder if the author has considered these matters.

Second, some studies have shown that LT4 use is associated with an increased risk of cancers, especially for brain and skin cancers. ³ This risk may be related to cumulative treatment time and dose of LT4. So we think the administration of LT4 should be more deliberate.

Third, the effect of TSH level on AS thyroid cancer outcomes is also controversial. Sugitani et al. indicated that no significant association between TSH and tumor progression was verified, and TSH was not a good predictor of tumor growth. ⁴ Another article from the same cohort found young patients with PTMC were more likely to experience tumor growth, and these patients might be the biggest beneficiaries. ⁵ We wonder whether we should pay more attention to individualized treatment, especially young patients. Mild TSH suppression may not be applicable for all patients.

In summary, due to the controversy of TSH suppression and on clinical and thyroid cancer outcomes in AS, more evidence is needed before drawing firm conclusions.