Medullary Thyroid Cancer Responsiveness to Pentagastrin Stimulation: An Early Surrogate Parameter of Tumor Dissemination?

Abstract

Abstract Context: Because of its outstanding sensitivity, stimulation of calcitonin secretion with iv injection of pentagastrin is widely used for biochemical diagnosis of medullary thyroid cancer. Objective: The objective of this study was to explore the relationship between the results of the pentagastrin stimulation test and extent of disease in patients with previously untreated medullary thyroid cancer. Design: This was a retrospective study. Setting: The investigation took place at a tertiary referral center. Patients: Included were 89 patients with increased basal calcitonin levels who had a pentagastrin test at this institution before initial neck surgery for medullary thyroid cancer. Main Outcome Measure: Measurements included basal and stimulated calcitonin levels, carcinoembryonic antigen levels, primary tumor diameter, extrathyroidal extension, lymph node metastases, and distant metastases. Results: There was a strong dose-dependent relationship between a less than 10-fold increase in preoperative calcitonin levels after iv stimulation with pentagastrin and both the frequency (41–54 vs. 4–27%; P = 0.001) and number (means of 3.0–10.8 vs. 0–1.1 positive nodes, P < 0.001) of lymph node metastases. Weaker associations were identified with the respective frequency of extrathyroidal extension (14–27 vs. 0–7%; P = 0.027), distant metastasis (9–23 vs. 0%; P = 0.017), and postoperative normalization of calcitonin (40–55 vs. 53–82%; P = 0.029). On multivariate analysis, only lymph node metastases were associated with a less than 10-fold increase in preoperative calcitonin levels. Conclusions: Based on these clinical data and preclinical literature, reduced responsiveness to stimulation with pentagastrin may reflect early dedifferentiation. Evidence of this condition may enable early risk stratification in patients with medullary thyroid cancer.