BACKGROUND
Papillary thyroid cancer is the most common type of thyroid cancer. Fortunately, papillary thyroid cancer is generally a slow-growing cancer. The initial treatment of thyroid cancer is surgery to remove the thyroid. When the entire thyroid gland is removed in the treatment of thyroid cancer it is called a total thyroidectomy. If the cancer removed is moderate to high risk, a total thyroidectomy may be followed by radioactive iodine therapy to destroy both the remaining normal thyroid cells as well as the cancer cells.

Thyroglobulin is a protein only produced by thyroid cells, both normal and cancerous. After a total thyroidectomy, and especially after radioactive iodine therapy, the thyroglobulin level can be used as a cancer marker. If the thyroglobulin level is barely detectable or undetectable, it is likely that there is no significant thyroid cancer present in the body. If the thyroglobulin level is detectable but stable, that likely means that there may be thyroid tissue present that may include cancer but the cancer is not growing or spreading. If the thyroglobulin level increases over time, then it is likely that thyroid cancer is present and is growing.

The time needed for a patient’s thyroglobulin level to double can also be studied. The measurement of the thyroglobulin doubling time and the thyroglobulin doubling rate are more recently being studied to see if they might predict a thyroid cancer recurrence. This study combines the thyroglobulin levels obtained after total thyroidectomy and the thyroglobulin doubling rate to see if they accurately predict a thyroid cancer recurrence.

THE FULL ARTICLE TITLE
Ito Y, et al. Dynamic risk assessment using unstimulated serum thyroglobulin level and thyroglobulin doubling rate after total thyroidectomy for papillary thyroid carcinoma. Thyroid. Epub 2025 Aug 11; doi: 10.1177/10507256251367242. PMID: 40794485.

SUMMARY OF THE STUDY
This study included 1,818 patients from the Kuma hospital in Japan from 2012 to 2022 who had total thyroidectomies were studied to see if papillary thyroid cancer was found in the surgical specimen. The doubling time of the thyroglobulin was calculated from three measurements obtained after the surgery. Patients were studied to see if they had a cancer recurrence in the neck or other areas of the body.

From the 131 patients (7%) who had thyroglobulin levels above 3 mg/dL, 88 patients had recurrences in the neck and 32 patients had recurrences in other parts of the body. As the thyroglobulin level went up, the chance of having a recurrence in the neck or other part of the body increased. Out of 1,245 patients, 119 (9.6%) had thyroglobulin doubling rates of more than 0.33/ year and had an increased risk of a neck cancer recurrence or a cancer recurrence in another area of the body.

A total of 1,212 patients who did not receive radioactive iodine therapy and 290 patients who received low dose radioactive iodine therapy were studied. The patients with the most recurrence of thyroid cancer in the neck (97.7% in 10 years) and recurrences other places in the body (99.5% in 10 years) had a thyroglobulin level of >3 ng/ml and a thyroglobulin doubling rate of >0.33/year. These outcomes were worse than those patients who had EITHER a thyroglobulin level <3 ng/mL OR a thyroglobulin doubling rate of <0.33/year. There was not an important difference in outcomes among the patients who had either <3 ng/mL of thyroglobulin level OR a thyroglobulin doubling rate of <0.33/year.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
These data suggest that a thyroglobulin level of >3 mg/ dL corresponded to cancers sized >4 cm and detection age of >55. If the thyroglobulin is >3 mg/dL and the thyroglobulin doubling rate is >0.33 mg/dL per year, the risk of having a cancer recurrence around the neck or other area of the body is higher. Only 1% of patients fall into this category meeting BOTH thresholds and should be more closely monitored. Most patients (80%) did not meet the threshold of EITHER these numbers and have a low risk of recurrence.

During a time when patients are treated with less radioactive iodine, patients might have higher baseline thyroglobulin levels after surgery. Incorporating a doubling rate of thyroglobulin might help separate normal thyroid tissue from more aggressive thyroid cancers producing the thyroglobulin. In addition, now physicians are using lower doses of levothyroxine to protect patients’ heart and bone health, which can also result in higher thyroglobulin levels. Combining the thyroglobulin level and the doubling rate of the thyroglobulin might more accurately predict thyroid cancer recurrences.

— Pinar Smith, MD

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