Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories

Abstract

Objective: We aimed to determine whether the ratio of thyrotropin (TSH) to thyroglobulin (Tg) (TSH/Tg) would be able to assist in predicting malignancy in thyroid nodules. Material and Methods: Euthyroid patients operated between the year 2007 and 2014 were retrospectively reviewed. Patients who previously had thyroid disease or surgery and those with increased levels of anti-thyroglobulin antibodies were excluded from this study. Clinicopathological features, as well as serum TSH, Tg, and TSH/Tg were compared between histopathologically benign and malignant groups. Results: Data related to 370 (60.3%) benign and 244 (39.7%) malignant patients were analyzed. The malignant patients exhibited significantly higher TSH, TSH/Tg, and total thyroid volume, and a lower Tg compared to the benign patients (p<0.001 for each). There were 924 (74.2%) benign and 321 (25.8%) malignant nodules. Cytological distribution of the nodules was observed to be as follows: 343 (27.6%) nondiagnostic, 637 (51.2%) benign, 121 (9.7%) atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 39 (3.1%) follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 64 (5.1%) suspicious for malignancy (SM), and 41 (3.3%) malignant. TSH, Tg, and TSH/Tg were significantly different in different Bethesda categories (p<0.001 for each). Median TSH/Tg was the lowest in benign (0.013), and highest in SM (0.054) and malignant (0.086) cytologies. TSH/Tg was significantly higher in the malignant nodules compared to benign nodules, in AUS/FLUS, FN/SFN, and SM categories (p=0.001, p<0.001, and p=0.003, respectively). In the regression analysis, TSH/Tg demonstrated higher diagnostic performance compared to TSH and Tg (p<0.001). Discussion: Preoperative TSH/Tg could be used as a novel marker for differentiating between benign and malignant thyroid nodules. It could also assist in the prediction of risk of malignancy and management decisions when the cytology is indeterminate. Keywords

The diagnostic and predictive accuracy of thyroglobulin to TSH ratio and TSH to thyroglobulin ratio in detecting differentiated thyroid carcinoma in normothyroid patients with thyroid nodules: A retrospective cohort study and systematic review of the literature

“…Specifically, Tam et al reported that the median and range values in the benign and malignant group were 0.02 μIU/ng (0.001-1.09) and 0.04 (0.001-2.24) respectively (P<0.001). 13 Similar results were reported by Yazici et al (0.02 (0.004-8.6) vs 0.04 (0.002-19) μIU/ng respectively, P=0.024). 14 Wang et al .…”

“…Reviewing the data of the literature we observed that at least two studies reported significant differences in TSH/Tg ratios between patients with benign and malignant disease, although they were discrete with a very large range. 13 , 14 This latter observation significantly hinders the application of this ratio to clinical practice as a diagnostic and surveillance biomarker. Most of the studies failed to report actual 95% confidence intervals with their results being potentially affected by significant outliers; hence, it remains unknown whether the range of the true value of these ratios is associated with clinical relevance.…”

Determination of Diagnostic Features of Serum Thyroid Hormones and Thyroglobulin Ratios in Normothyroid Differentiated Thyroid Carcinoma Cases

“…In our study, the cutoff value for TG/TSH was determined as 29.67. In their study with 244 malignant patients, Tam et al [ 16 ] reported that the TSH/TG ratio could be used as a novel marker to differentiate benign and malignant thyroid nodules in the pre-operative period and that it could help to determine the malignancy risk in nodules with indeterminate cytology and help the management of these patients. Wang et al [ 12 ] found that increased serum TSH/TG (cutoff=0.024) in the pre-operative period was associated with thyroid malignancies at a higher rate compared to TSH alone.…”