Characteristics of patients and thyroid nodules
A total of 235 thyroid nodules in 212 patients participated in the study. The histopathological diagnoses of these nodules included nodular goiter (62 nodules), chronic thyroiditis (three nodules), follicular neoplasm (14 nodules), papillary carcinoma (135 nodules), follicular carcinoma (four nodules) and medullary carcinoma (17 nodules) (Table 1). The median age of the patients was 42 years (range, 16-82). A total of 50 males (23.6%) and 162 females (76.4%) were included. The age range of the healthy subjects was 22 to 84 years. A total of 1,126 males (58.0%) and 815 females (42.0%) were included in the healthy group. Clinical stage included stage Ⅰ (117), stage Ⅱ (4), stage Ⅲ (13), stage Ⅳa (9) and stage Ⅳc (1) (Table 2). Form of MTC included sporadic MTC (10) and hereditary MTC (3).
Serum CT in patients with thyroid nodules
It was clearly seen that concentrations of serum CT in MTC was significantly higher compared with the other subjects. Significantly increased was observed in papillary thyroid carcinoma compared with the healthy groups (Table 3, Figure 1). Statistical significant differences were shown between different stages: MTC stage Ⅰ+Ⅱ and no-MTC stage Ⅰ+Ⅱ, MTC stage Ⅰ+Ⅱ and no-MTC stage Ⅲ+Ⅳ, MTC stage Ⅲ+Ⅳ and no-MTC stage Ⅰ+Ⅱ, MTC stage Ⅲ+Ⅳ and no-MTC stage Ⅲ+Ⅳ, with a p-value of < 0.001, < 0.001, < 0.001 and < 0.001, respectively (Figure 2). In the healthy subjects, the 95th percentile of the serum CT levels was 13.8 pg/mL, which was used as a cutoff point for CT positive samples. The abnormal CT levels were noted for 100.0% in medullary thyroid carcinoma (Table 3). Statistical significant differences were shown in serum CT between Medullary thyroid carcinoma and healthy groups.
The concentrations of FNA-CT in nodular goiter, chronic thyroiditis, follicular adenoma, papillary carcinoma, follicular thyroid carcinoma and medullary thyroid carcinoma were 2.0 (5.8) pg/mL, 2.1 pg/mL, 2.2 (6.2) pg/mL, 2.0 (5.5) pg/mL, 4.8 (6.6) pg/mL and 5000.0 (1660.2) pg/mL, respectively. Significantly higher concentrations were found in medullary carcinoma compared with the other subjects (Figure 3).
FNA-CT/Serum-CT ratio in thyroid nodules
The ratio of FNA-CT/Serum-CT in nodular goiter, chronic thyroiditis, follicular adenoma, papillary carcinoma, follicular thyroid carcinoma and medullary thyroid carcinoma were 1.00 (0.93), 0.61, 0.64 (1.01), 0.69 (0.87), 0.96 (1.37) and 4.44 (19.68), respectively. Significantly higher ratio were found in medullary carcinoma compared with the other subjects (Figure 4).
CT in different form of MTC
There were ten cases of sporadic MTC and three cases of hereditary MTC. Statistical significant differences weren’t shown in CT concentration between sporadic MTC and hereditary MTC (Figure 5).
Clinical Diagnosis of CT
In a receiver operating characteristic (ROC) analysis of the MTC, the area under the curve (AUC) of serum CT, FNA-CT and FNA-CT/serum CT ratio were 1.000, 0.998 and 0.887 respectively (Table 4, Figure 6). The cutoff value of serum CT was 13.8 pg/mL, leading to a sensitivity of 100.00% and a specificity of 97.99%. The cutoff value of FNA-CT was 91.6pg/mL, leading to 100.00% sensitivity and 97.25% specificity. The cutoff value of FNA-CT/serum CT ratio was 0.99, leading to 100.00% sensitivity and 51.83% respectively (Table 5, Figure 6). The Kappa values of serum CT, FNA-CT, FNA-CT/serum CT ratio and FNAC were 0.86, 0.84, 0.14 and 0.90, respectively (Table 5).
Serum CT were determined to be false-positive in four patients. FNA-CT were determined to be false-positive in six patients. There was no overlap in the patients who had false positive results with the use of the two methods (Table 6).