Calcitonin testing in patients with thyroid nodules for screening medullary thyroid carcinoma: a “gray zone”

Abstract

Introduction. The results of the calcitonin (Ctn) study in patients with thyroid nodules are included in the clinical guidelines for the treatment of differentiated thyroid cancer. However, the management of patients with moderately elevated Ctn up to 100 pg/mL is not clearly defined.Materials and methods. The study included 103 patients with thyroid nodules and a Ctn level above the reference, but not more than 100 pg/ml. The Ctn concentration was determined using the Cobas e platform (Roche, Germany) or by the immunoradiometric method (Izotop, Hungary). 45 patients were operated on. The analysis of the incidence of medullary thyroid carcinoma (MTC), other thyroid and nonthyroid pathology in patients with elevated Ctn scan was carried out. The results of additional examination are presented: the serum cancer embryonic antigen, Ctn in wash-out, stimulated Ctn, gene RET mutation testing.The study objective is to evaluate the probability MTC with Ctn level <100 pg/ml, propose management tactics for patients with elevated Ctn and negative cytological results.Results. The incidence of MTC was 22 % (23/103). The maximum probability of mTC was at Ctn above 50 pg/mL (81 %, 13/16), at Ctn 31-50 pg/mL mTC was detected in 38 % (3/8). With Ctn <30 pg/mL and <20 pg/mL, the incidence of MTC was 9 % (7/79) and 6 % (4/64), respectively. In the majority of MTC patients (65 %), the tumor size did not exceed 1 cm. However, 22 % (5/23) had metastases to the neck lymph nodes. postoperative Ctn normalization was achieved in 96 % (22/23). In 26 % (5/19), a RET germ-line mutation was detected, most often p.val804met.Among patients without MTC, other thyroid tumors were found in 35 % (28/80), more often papillary thyroid cancer (25 %, 20/80). 13 % (10/80) had other malignant neoplasms. parathyroid adenoma was detected in 3 % (2/80). The maximum Ctn in this group was in patients with chronic kidney disease and metastatic liver disease with cholestasis and ascites.Cancer embryonic antigen was increased in 53 % of patients with MTC and in 7 % of patients without MTC. Ctn in washout was >2000 pg/mL in mTC and up to 938 pg/mL in patients with histologically confirmed absence of MTC.Conclusion. If the Ctn level is <100 pg/mL and there is no cytological confirmation, the issue of surgery is decided individually, taking into account many factors. After excluding other causes of hypercalcitoninemia (hyperparathyroidism, kidney disease, other tumors), measurement of serum cancer embryonic antigen and Ctn in wash-out is recommended. In some cases, testing for a RET mutation can be helpful.

Keywords

• calcitonin
• cancer embryonic antigen
• medullary thyroid carcinoma
• screening
• <i>ret</i>