The clinical significance of thyrotropin (TSH) in the preoperative differential diagnosis of benign and malignant thyroid nodules

Background Thyroid nodules diseases are common, and fine-needle aspiration biopsy (FNAB) is the first choice in distinguishing benign disease from malignant one. A part of patients whose results of FNAB are indeterminate (Thy3, Thy4) underwent surgery while postoperative pathology reported benign lesions. Serum thyrotropin (TSH) is a known thyroid growth factor, and suppression of TSH concentrations by administering exogenous thyroxine may influence the growth of established nodules as well as the formation of new thyroid nodules, however the pathogenic role of TSH in thyroid oncogenesis is unclear. The aim of this study is to examine the relationship between preoperative TSH and differentiated thyroid cancer (DTC) and investigate whether TSH at presentation can serve as a predictor of thyroid malignancy in patients with thyroid nodules. Methods Between 2011 and 2014, a total of 9774 patients underwent thyroid surgery in our department. Data from 1287 patients without overt thyroid dysfunction with preoperative serum TSH concentration were recorded. Age, gender, nodule number, nodule size, preoperative fine-needle aspiration biopsy (FNAB), and serum TSH level were assessed in relationship to the postoperative pathological outcomes. Patients were divided into subgroups according to results of pathology, TSH level, DTC stage, and patient’s age, then the relationship between TSH and thyroid cancer was analyzed. Results The overall sensitivity and specificity of FNAB in predicting malignancy were 82.9% and 91.9%, respectively. 223 patients (17.3%) had DTC on final pathology. Serum TSH levels in DTC patients (mean 1.20 ±0.1 uU/ml) were significantly higher than in benign thyroid nodule disease (BTND) (mean 0.80 ±0.3uU/ml). The risk of diagnosis of malignancy correlated with higher TSH level at presentation, with significant higher rates of malignancy observed in patients with serum TSH greater than 0.9 uU/ml, compared with those with lower TSH. The mean TSH was 2.80 ±1.6 uU/ml in patients with stage III/IV vs. 0.74±0.3 uU/ml in patients with stage I/II (P= 0.003). In thyroid auto-antibody (TAb) positive subjects, mean TSH level (0.80±0.3 uU/ml) was significantly higher (P=0.002) than in TAb negative patients (0.60±0.5 mU/m). Both in TAb positive and negative patients, serum TSH levels were significantly higher in DTC than in BTND group. Mean TSH level was significantly higher in cancer patients regardless of age < 45 years or ≥ 45 years (P =0.045 and 0.028, respectively). When age groups < 30, 30–44, 45–59 and ≥60 years were examined, it was found that there was a trend of rising mean TSH with age. Despite the similar rise in the benign subgroups, mean TSH level was consistently higher in those with cancer vs. those without. On multivariate analysis, higher TSH was independently associated with cancer (P=0.039) but not with age (P=0.458). Binary logistic regression analysis revealed significantly increased adjusted odds ratios (AOR) for the diagnosis of malignancy in patients with serum TSH 0.60-0.89 uU/ml when compared with those with TSH <0.60 uU/ml, with further increase evident in those with TSH 0.9-1.59 uU/ml, 1.60-3.4 uU/ml, and greater than 3.4 uU/ml compared with TSH<0.60 uU/ml. Males (AOR 2.42, 95% CI 1.53-3.57, P <0.0001), younger patients (AOR 0.92, 95% CI 0.88-0.97, P=0.026), and those with solitary nodules (AOR 2.34, 95% CI 1.49-4.16, P=0.001) and smaller nodules (AOR 0.72, 95% CI 0.68-0.89, P<0.0001) were also at an increased risk. Conclusion TSH is a known thyroid growth factor and the risk of malignancy in thyroid nodules increased with higher serum TSH concentration. Even within normal TSH ranges, an increased risk of DTC was found in a TSH level above the population mean relative to a TSH level below the mean. In addition, higher serum TSH concentration is related to advanced stage DTC. Despite unclear pathogenesis, the association between thyroid cancer and higher TSH is independent of age. Serum TSH level may be able to serve as an adjunct to other well defined clinical parameters and results of FNAB, especially for the indeterminate cytologic outcome.