Optimal Thyrotropin Following Lobectomy for Papillary Thyroid Cancer: Does It Exist?

As thyroid cancer management has trended toward an individualized approach, low-risk disease is often treated with thyroid lobectomy, instead of total thyroidectomy. Benefits of lobectomy include lower surgical risk and potential to avoid lifelong thyroid hormone replacement. Several studies found that 70–80% of patients who undergo thyroid lobectomy can avoid thyroid hormone replacement (1,2). These specific patient populations had normal thyroid function preoperatively and hypothyroidism was defined as a thyrotropin (TSH) above the normal reference range. However, if goal TSH level is 0.5–2.0 mIU/L, consistent with the 2015 American Thyroid Association (ATA) guidelines' TSH goal for low-risk thyroid cancer (3), then the proportion of patients potentially requiring thyroid hormone replacement after lobectomy is much higher. In a study by Schumm et al., out of 115 patients who underwent lobectomy for thyroid carcinoma, 92 (80%) had a TSH ≥2 mIU/L in the first 6 months after surgery, with 68% of these patients started on levothyroxine a median of 74 days postoperatively (4). Cox et al. reviewed 478 patients with normal thyroid function preoperatively, who underwent lobectomy for papillary thyroid cancer and similarly found that 73% had a TSH of >2 mIU/L within a year (5). Since the ability to avoid thyroid hormone replacement is directly related to TSH goal, the question of whether a lower TSH range reduces the risk of recurrence in patients postlobectomy for thyroid cancer is clinically important.

This study by Xu et al. is a single-center retrospective cohort study of 2297 patients who underwent lobectomy for thyroid cancer, were recommended thyroid hormone replacement, and then were evaluated for the impact of TSH on recurrence (6). While the authors excluded high-risk variants, preoperative evidence of distant metastasis, and positive margins, the study population included 42.4% patients who were intermediate risk and 16.4% high risk for recurrence, as defined by the 2015 ATA guidelines. Importantly, many of the patients treated with lobectomy in this study would not be candidates for lobectomy per the 2015 ATA guidelines. The high proportion of intermediate and high-risk disease contributed to structural recurrence in 7.3% with 11 patients dying from thyroid cancer. However, despite the median follow-up of 70 months and relatively high proportion with recurrence, mean TSH was not found to impact recurrence, including in the adjusted model restricted to patients with intermediate and high risk for recurrence.

There is conflicting data on the relationship between TSH and recurrence in patients treated with lobectomy. A previous study by Park et al. retrospectively reviewed the characteristics of 1047 patients who underwent thyroid lobectomy for low- or intermediate-risk papillary thyroid cancer and reported that TSH level at 1 year was an independent risk factor for recurrence, with recurrence more frequent with a TSH >1.85 mIU/L (7). A study by Lee et al. (8) retrospectively reviewed 1528 patients who underwent thyroid lobectomy for low-risk disease and found that during 5.6 years of follow-up, there was no difference in recurrence among patients with TSH ranges from <0.5, 0.5–1.9, 2.0–4.4, or >4.5 mIU/L. This study also looked at the impact of levothyroxine use on recurrence and found that, while those on thyroid hormone replacement had a lower mean TSH than those who were not on thyroid hormone replacement, there was no difference in recurrence (8).

Xu et al.'s study included a larger population than the earlier studies and the cohort had a higher recurrence rate (6). However, there are some limitations. First, the retrospective study design could introduce selection bias. In addition, more than half of the patients had tumors <1 cm, which per the ATA guidelines should not routinely be biopsied, much less resected. The inclusion of both these small tumors and intermediate- to high-risk disease could decrease generalizability to the populations in whom lobectomy is recommended.

The potential to avoid lifelong thyroid hormone replacement is a major benefit of lobectomy over total thyroidectomy. Avoidance of thyroid hormone replacement may have financial and psychological importance to patients, particularly those who are young and lack other medical conditions. Taking a daily pill, refilling prescriptions, and having routine laboratory testing medicalize an individual and can negatively impact on quality of life. However, the ability to avoid thyroid hormone replacement after lobectomy is directly related to TSH goal. Many patients with postoperative TSH levels in the normal range but >2 mIU/L would require supplemental levothyroxine to achieve this lower target TSH of 0.5–2.0 mIU/L. However, there remains uncertainty as to whether physicians should target this lower TSH range as there is conflicting data on optimal TSH range to prevent recurrence postlobectomy. Xu et al.'s study is a helpful addition to the limited pool of data addressing this very important clinical question (6).