Mildly Elevated Basal Calcitonin Level in Patients With Thyroid Goiter: Using the Calcitonin Measurement in Fine-Needle Aspirate Washout Fluid of the Healthy Lobe to Define Medullary Thyroid Cancer and Reactive C-Cell Hyperplasia
Authors: Chevais Anastassia , Mikheenkov Alexander , Beltsevich Dmitry , Vanushko Vladimir , Melnichenko Galina A , Pokrovskaya Elena 
Published: May 2021

Abstract
Background: Mildly elevated basal calcitonin level (bCT), that suggests a bCT increase up to 100 pg/ml, may testify either medullary thyroid carcinoma (MTC) or reactive thyroid C-cell hyperplasia (CCH). The latter is observed under many conditions such as hypercalcemia, hypergastrinemia, thyroiditis, neuroendocrine tumors (NET), renal end-stage kidney disease, obesity, and smoking. The research is aimed at analyzing the clinical significance of the calcitonin measurement in the fine needle aspiration washout fluid sample (FNA-CT) for screening certain patients with nodular thyroidopathy and elevated bCT.
Patients and Methods: 70 patients with mildly elevated bCT (for women 6-100 pg/ml, for men 19-100 pg/ml) underwent ultrasound-guided FNA-CT measurement of the thyroid nodules and healthy lobe tissue. After obtaining a FNA-CT specimen, the needle was washed with 0.5 ml of saline solution. The calcitonin (CT) was measured by ECLIA (LIAISON XL).
Results: There were 51 females and 19 males, with a mean age of 46.8 ± 14.4 years (range 16-81). The mean value of bCT was 23.3 ± 19 pg/ml (range: 7-86.5). According to ultrasound, 66 patients (95%) presented with thyroid nodules, in 4 cases previously identified nodes were not confirmed. The mean lesion size was 10.8 ± 4.9 mm (range: 4-26). Thyroid nodules were evaluated by FNA biopsy which revealed according to the Bethesda system category I in 6 cases, II - 44, III - 2, IV - 4, V - 6, and VI - 1. Analyzing FNA-CT results we identified 13 cases (18%) with MTC with low CT level of healthy lobe tissue (1-89.6 pg/ml) and high CT level of the lesion (&gt;2000 pg/ml), which was confirmed by final histological examination. Low CT level from both healthy lobe and the nodule (&lt;20 pg/ml) was observed in 10 cases, we carried out the measurement of stimulated CT to exclude the extrathyroidal CT production, which was confirmed in 1 case. All 4 patients with no nodules possessed significantly higher T-rates (1650-2000 pg/ml). The remaining 43 cases (61%) had an increased CT-level of healthy tissue (&gt;2000 pg/ml) with a lower level from the lesion. Among these patients, the probable predisposing CCH factors were obesity - 8 cases, thyroiditis - 12, NET - 3, hypercalcemia - 3, renal kidney disease - 1, and smoking - 3. These 54 patients were kept under dynamic control. The observation period for patients - 1 year. 4 patients underwent surgical treatment, subsequently, histological examination revealed papillary thyroid cancer, follicular adenoma, colloid goiter against CCH, and CT-producing NET.
Conclusion: The measurement of FNA-CT of the healthy lobe tissue may be useful to differentiate MTC and CCH, but requires new data in a major cohort of patients. The disadvantage of this study is the impossibility of CCH histological verification in the follow-up group.