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Can serum calcitonin levels be used determine postoperative follow-up in medullary thyroid cancer?

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Medullary thyroid cancer (MTC) is a relatively rare type of thyroid cancer. While it is the 3rd most common type of thyroid cancer, it only comprises ~3% of all cases of thyroid cancer.

However, MTC is generally more aggressive than the most common type of thyroid cancer (papillary) and it is often found after it had already spread outside the thyroid. About 25% of all MTCs are genetic (ie run in families). A specific gene (RET) mutation can be detected in patients with the genetic forms of MTC and can be used to identify patients in a family that have MTC before it spreads outside the thyroid. Unlike the most common types of thyroid cancer (papillary and follicular thyroid cancer) which come from the thyroid follicular cells (which produce the thyroid hormones), MTC comes from the C-cells of the thyroid. The C-cells produce the hormone calcitonin, which is also used as a marker of MTC.

Surgery is the mainstay of treatment for MTC. In early stage MTC, in which the cancer has not spread outside the thyroid, surgery can cure MTC. Follow-up of MTC after surgery uses imaging (ultrasound) and measurement of calcitonin levels to determine if the disease is cured or if there are still cancer cells present. In this study, the authors measured calcitonin levels after thyroid surgery to assess cure.

Duval MAS et al 2023 An undetectable postoperative calcitonin level is associated with long-term disease-free survival in medullary thyroid carcinoma: Results of a retrospective cohort study. Thyroid 33:82–90. PMID: 36222615.

The authors studied 334 patients with MTC who underwent total thyroidectomy in two hospitals in Brazil, between 1997 and 2019. Calcitonin was initially measured 3-6 months after thyroid surgery and then every 6-12 months for an average of 7 years. Overall, 60% of patients were women and 40% were familial cancers. Half of the patients had spread of the cancer to the lymph nodes at the time of the surgery. About 40% of the patients had an undetectable calcitonin level after surgery. This group of patients, as compared to those who had detectable levels of calcitonin, were younger and their cancers were more likely to have been found by screening (due to family history). They had smaller cancers and less frequent spread to the lymph nodes. At their last follow-up, 90% of patients with undetectable calcitonin levels after surgery remained without evidence of MTC and 10% had stable levels without evidence of spread. There were no deaths in this group. On the other hand, in the group of patients who had detectable calcitonin levels after surgery, only 9% were free of cancer at their last visit, and 1/3 of the patients had died.

This study confirms that surgery is the best treatment to cure MTC. Finding an undetectable calcitonin level after surgery predicts cure. Many of the patients in the group with undetectable calcitonin level were those found by RET gene screening. This emphasizes the importance of genetic screening in patients at risk for the familial forms of MTC and recommending early thyroidectomy in those with the genetic mutation.

— Susana Ebner MD


Medullary thyroid cancer: a relatively rare type of thyroid cancer that often runs in families. Medullary cancer arises from the C-cells in the thyroid. The familial form is caused by the RET gene mutation.

Calcitonin: a hormone that is secreted by cells in the thyroid (C-cells) that has a minor effect on blood calcium levels. Calcitonin levels are increased in patients with medullary thyroid cancer.

Mutation: A permanent change in one of the genes.

Genes: a molecular unit of heredity of a living organism. Living beings depend on genes, as they code for all proteins and RNA chains that have functions in a cell. Genes hold the information to build and maintain an organism’s cells and pass genetic traits to offspring.

Thyroidectomy: surgery to remove the entire thyroid gland. When the entire thyroid is removed it is termed a total thyroidectomy. When less is removed, such as in removal of a lobe, it is termed a partial thyroidectomy.

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