Calcitonin-negative (Ct-negative) medullary thyroid carcinoma (MTC) is a rare form of the disease which appears to have a good prognosis for most patients according to a study published in Frontiers in Endocrinology.

Of the 312 patients with MTC included in the study, only 24 were found to be Ct-negative yielding an incidence of just under 8%. Previous studies had estimated incidence ranges from .83% to 12.0% of MTC cases. The authors attributed the range potentially to differences in detection reagents and methods.

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Lymph node metastasis is much less likely to appear in Ct-negative patients compared to Ct-positive patients with none of the Ct-negative patients experiencing lymph node metastasis compared to 47.9% of the Ct-positive patients.

All of the Ct-negative patients also only had a single focus with no cases of concurrent papillary thyroid carcinoma (PTC) or other malignant tumors. In comparison, 20 patients had multiple tumor foci and 30 had PTC in the Ct-positive group. No cases of RET gene mutations or familial MTC were detected in the Ct-negative group compared to 6 RET mutations and 1 familial MTC case in the Ct-positive group.

The extent of surgery was also statistically different between the 2 groups (P <.001) with all Ct-positive patients receiving total thyroidectomy with central neck dissection compared to only 7 of the 24 Ct-negative patients (29.2%). The remaining 17 Ct-negative patients only required a unilateral lobectomy with central neck dissection. Lateral neck dissections were also required in 88 of the Ct-positive cases (30.6%) but in none of the Ct-negative cases.

The rate of excellent response after treatment, as defined as a status of undetectable levels of Ct and no evidence of structural disease, was much higher in the Ct-negative patients, as well. Excellent response was achieved in 91.7% of the Ct-negative patients compared to 34.7% in the Ct-positive group (P <.001). An excellent response rate of 100% was achieved in 100% of the female Ct-negative patients (20 out of 20) compared to only a 50% rate in the male patients (2 out of 4).

“This study found that, compared to typical MTC, Ct-negative MTC tended to have limited capacity of lymph node metastasis and proliferation, and a good prognosis independent of the operation extent. However, male patients might require more aggressive treatment,” the authors said.


Yue W, Zhang Y. Oncologic outcomes of calcitonin-negative medullary thyroid carcinoma. Front Endocrinol. Published online November 23, 2022. doi:10.3389/fendo.2022.1025629