Preoperative Calcitonin Levels Are Predictive of Tumor Size and Postoperative Calcitonin Normalization in Medullary Thyroid Carcinoma

Abstract

Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting endocrine tumor. Although plasma CT level is a specific and sensitive marker of MTC, its preoperative usefulness in predicting tumor size and postoperative CT normalization has not been documented. From a nationwide database set up by the French CT Tumor Study Group, 226 MTC patients were selected according to the following criteria: preoperative CT level determination by an immunoradiometric assay (normal value, < 10 pg/mL) within the 6 months prior to surgery, total thyroidectomy and diagnosis of MTC ascertained by histological report including tumor size. Patients were 129 females and 97 males (female/male ratio, 1.3). One hundred and twelve patients (49.6%) had the sporadic variety of the disease, 74 (32.7%) had multiple endocrine neoplasia 2A, three (1.3%) had multiple endocrine neoplasia 2B, and 37 (16.4%) had familial MTC. Median age at diagnosis was 44.8 yr (range, 4.9-80.1 yr). Complete neck dissection was performed in 159 patients (70.4%). Postoperative CT normalization was ascertained by negative response of CT to pentagastrin stimulation (< 10 pg/mL) in 94 patients. Seventy-one patients were considered as not cured because of residual tumor tissue and/or elevated CT levels. Median tumor size was 11.0 mm (range, 0.2-80.0 mm), significantly larger in females (15.0 vs. 8.0 mm, P < 0.05), and in sporadic forms (15.0 vs. 7.0 mm, P < 0.05). Tumor size was significantly correlated (r2 = 0.52, P < 0.01) with preoperative CT levels, the relationship being more straight in familial (r2 = 0.71) than in sporadic (r2 = 0.36) forms. Furthermore, preoperative CT levels under 50 pg/mL appeared to be predictive of postoperative CT normalization (44 of 45 patients). However, higher CT levels did not mean absence of postoperative CT normalization (50 of 120 patients). We conclude that low preoperative CT levels are predictive of tumor size and postoperative CT normalization.

Surgical management of medullary thyroid cancer: which guidelines should we follow?

“…An alternative to utilising TNM disease staging to stratify risk and determine surgical strategy is to utilise the pre-operative basal calcitonin level. This measure has been shown to correlate with primary tumour size, the number of lymph node metastases and the post-operative biochemical cure rate 18 , 23 , 24 . However, reliance upon a pre-operative diagnosis of medullary thyroid cancer is not always possible.…”

Disparity between tissue and serum calcitonin and carcinoembryonic antigen in a patient with medullary thyroid carcinoma

“…Immunostaining for calcitonin can also be used to detect C-cell hyperplasia, a precursor to clinical MTC [21,23]. Several studies demonstrate a correlation between tumor size and the basal calcitonin levels, although it can be difficult to distinguish benign processes from MTC based on a distinct calcitonin level threshold [24,25]. Although some case reports note that a few patients with MTC had normal basal serum calcitonin levels, in most of these cases the tumor cells show very weak or no calcitonin expression by immunohistochemistry, suggesting a loss of tumor expression of calcitonin [4,7,[11][12][13].…”

Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma

“…3). This is reminiscent of patients with MTC where calcitonin levels correlate with tumor burden (Cohen et al 2000). Given the pivotal role of RET in the development of human MTC, we sequenced the regions of the Ret gene corresponding to those where activating mutations occur in humans, in nine MTCs derived from p27+/mut rats, but no mutations were found (data not shown).…”