A Case of C-Cell Hyperplasia in an Asymptomatic V804M Ret Mutation Carrier: Can the Calcium Infusion Test Predict C-Cell Hyperplasia?

ABSTRACT Objective: Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma (MTC) are autosomal dominant inherited diseases caused by genetic mutations of the RET proto-oncogene. Prophylactic total thyroidectomy in carriers of activating RET proto-oncogenes, depending on mutation-based risk level, is recommended in the United States and many other countries. Measurement of calcitonin following stimulation with intravenous calcium gluconate has been widely adopted as a screening test for MTC. Methods: Here, we describe a carrier of the RET V804M mutation in whom total thyroidectomy was performed at age 54 years after a calcium infusion test with the only available insurance-reimbursable calcitonin assay (an earlier generation calcitonin assay than currently reported) was employed. The case's older brother, who was also a RET V804M mutation carrier, was diagnosed with MTC at the age of 60 years, and his mother died of thyroid cancer with systemic metastases at the age of 76 years. Results: During the calcium infusion test, the patient's serum calcitonin level increased from 40 to 161 pg/mL, a test result considered positive by the calcitonin assay specifications. C-cell hyperplasia, but not MTC, was noted in 2 of 11 thyroid tissue sections. Conclusion: Although data from a more recent calcitonin assay and further information regarding the patient's mother's thyroid cancer would have been ideal, the present report adds to the literature regarding the clinical impact of the RET V804M mutation and the lack of specificity of older calcitonin assays for the diagnosis of MTC. Abbreviations: MEN multiple endocrine neoplasia MTC medullary thyroid carcinoma RET rearranged during transfection