Management of postoperative hypercalcitoninemia in medullary thyroid carcinoma

Medullary thyroid cancer (MTC) is an uncommon tumor, representing 1-3% of human thyroid cancers, which derives from calcitonin-producing parafollicular C-cells. Twenty-five percent of MTC cases are familial and bear activating germline mutations in the RET gene, encoding a receptor tyrosine kinase. Among nonfamilial cases, 40% of tumors have somatic RET mutations, predominantly the high-risk M918T allele. Early nodal metastasis is a characteristic feature of MTC. Distant metastases involving the mediastinum, lung, liver, and bone become prevalent in patients with calcitonin levels >500 pg/mL. Management of postoperative hypercalcitoninemia in MTC focuses on initial prognostic assessment, based on TNM stage, calcitonin doubling time, and RET mutation status. Imaging decisions are keyed by the degree of calcitonin and CEA elevation. Treatment options include watchful waiting in many cases, reoperation with palliative or occasionally curative intent, rarely external beam radiation therapy, and oral tyrosine kinase inhibitors. Vandetanib and cabozantinib are first-generation, multikinase inhibitors with RET inhibitory activity. Selpercatinib is a second-generation, highly selective RET inhibitor.