BACKGROUND
Standard treatment for high-risk thyroid cancer patients includes total thyroidectomy followed by radioactive iodine treatment and thyroid hormone treatment to suppress TSH levels. Lowering the TSH level to less than 0.1 mU/L has been shown to decrease cancer recurrence and improve survival in high-risk thyroid cancer patients. However, TSH suppression can result in an increased risk for atrial fibrillation, bone loss and osteoporosis and an overall decrease in the quality of life.

Fortunately, most patients have low-risk thyroid cancer and treatment may be limited to removing only the lobe containing the thyroid cancer (lobectomy) and deferring radioactive iodine treatment. For low-risk thyroid cancer, the 2015 American Thyroid Association (ATA) guidelines recommend starting thyroid hormone treatment after the patients undergo either total thyroidectomy or lobectomy to keep the TSH in the low normal range (0.5-2.0 mU/L). However, the evidence behind this recommendation is limited. Starting thyroid hormone treatment requires laboratory monitoring and physician visits, which can increase the health care costs, while overtreatment can harm the patients. The goal of this study was to evaluate whether maintaining the TSH in the high normal range (2-4.0 mU/L) increases the recurrence risk as compared to the currently recommended low-normal TSH goal range (0.5-2.0 mU/L) in patients with low-risk thyroid cancer after thyroid surgery.

THE FULL ARTICLE TITLE
Qiang JK, et al. Association between serum thyrotropin and cancer recurrence in differentiated thyroid cancer: a population-based retrospective cohort study. Thyroid. Epub 2024 Dec 26; doi: 10.1089/thy.2024.0330. PMID: 39723994.

SUMMARY OF THE STUDY
This study included 26,336 patients with thyroid cancer included in the Ontario Cancer Registry between 2007 and 2018. This registry captures 99% of cancer cases in Ontario. Serum TSH values and the dates of measurement were obtained from the Ontario Laboratories Information System, which captures most outpatient laboratory tests in Ontario.

The study included patients older than 18 years of age diagnosed with thyroid cancer and who had at least one TSH test result recorded during follow-up. The patients started to be followed for TSH measurements and thyroid cancer recurrence 12 months after their initial thyroid surgery. The average serum TSH for 90-day intervals was used for analysis. The primary analysis evaluated the time from the initial thyroid surgery to thyroid cancer recurrence in the high normal TSH (2-4 mU/L) group as compared to the reference low normal TSH (0.5–2 mU/L) group. The recurrence in the TSH <0.5 mU/L and TSH >4 mU/L groups was also evaluated as secondary analysis. Recurrence was defined as the need for additional treatment, including new surgery or radioactive iodine treatment or death due to thyroid cancer after the initial surgery.

Most study patients were women (78%) living in urban centers (93%), with an average age of 50. A total of 21% of patients underwent lobectomy, 41% had total thyroidectomy, and 38% had total thyroidectomy followed by radioactive iodine treatment. The average follow-up was 5.9 years, and the average TSH was 0.6 mU/L. During the follow-up period, 2,817 (10%) patients had thyroid cancer recurrence. Among these patients, 361 (1.3%) underwent completion thyroidectomy, 689 (2.6%) had neck dissection, 1664 (6.3%) received radioactive iodine treatment, and 103 (0.3%) died from thyroid cancer.

There was no increase in the recurrence risk in patients maintained with a high normal TSH (2- 4 mU/L) levels as compared to the low normal TSH (0.5-2 mU/L) levels. However, there was a higher risk of thyroid cancer recurrence with exposure to TSH levels >4 mU/L as compared to low normal TSH range (0.5–2 mU/L). This was most apparent after 4 years of exposure to higher TSH levels.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Patients with low-risk thyroid cancer who maintained TSH levels in the high normal range (2 – 4 mU/L) had similar cancer recurrence rates as compared to those with TSH levels in the low normal range (0.5–2 mU/L), which is the currently recommended treatment target by the ATA guidelines. This is important data to consider when treating these patients. It also is clear that the recurrence risk increased when TSH was >4 mU/L. These results suggests that the serum TSH target could be broadened to 0.5–4 mU/L in patients with low-risk thyroid cancer. New ATA thyroid cancer guidelines will be published later this year and, hopefully, these new targets will be discussed.

— Alina Gavrila, MD, MMSC

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