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

Abstract

The purpose of the present study is to examine the diagnostic and predictive accuracy of the thyroglobulin (Tg) to thyroid stimulating hormone (TSH) and TSH/Tg ratios in normothyroid patients with differentiated thyroid cancer (DTC). We conducted a retrospective cohort study evaluating the diagnostic accuracy of the serum Tg/TSH and TSH/Tg ratios in normothyroid patients with thyroid nodules. We also systematically searched the international literature using the Medline, Cochrane’s CENTRAL, Scopus, Clinicaltrials.gov, EMBASE, and Google Scholar databases for evidence concerning the diagnostic and predictive accuracy of these ratios. Overall, 374 patients were identified in our cohort study of whom 240 were treated for benign disease and 134 were treated for DTC. Significant differences were noted in the Tg/TSH and TSH/Tg values among cases with malignant and benign disease (P=0.020). However, the diagnostic ROC curve did not confirm these results (Tg/TSH=0.572 and TSH/Tg=0.428). After searching the international literature, we identified 8 studies. The majority of the included data reported significant differences among patients with benign/malignant disease and those with successful iodine therapy compared to those with disease relapse. However, the clinical relevance was clearer among studies that investigated the usefulness of these ratios in predicting recurrent disease. The findings of our study support that the Tg/TSH ratio increases in patients with DTC and can, thus, become useful in the future as a predictive marker of ablative 131I therapy success. However, given the significant variability of Tg its diagnostic accuracy remains to date minimal; thus, the actual cut-off value that can be used to discriminate cancer cases from benign disease has not been determined yet.

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

“…Karvounis et al, [ 13 ] proposed that TG/TSH and/or TSH/TG ratios could be a marker of malignancy, with the hypothesis that malignant cells may respond differently to TSH than benign cells since TSH is a factor that directly affects the secretion of TG. In their study, they found that both TG/TSH and TSH/TG ratios differed significantly between malignant and BGs in univariate analysis.…”

“…They determined the cutoff value for the TG/TSH ratio as 15.6 ng/mIU. [ 13 ] In our large series of 402 patients with DTC, we observed significant differences in the TG/TSH ratio (14.36 [0.04–13100.0] vs. 62.75 [0.09–3265.0], p≤0.001) and TSH/TG ratio (1.25 [0.000076–22.48] vs. 0.01 [0.0003–10.60], p≤0.001), and we demonstrated these results in the diagnostic ROC analysis (p≤0.001 for TG/TSH, p<0.001 for TSH/TG). In our study, the cutoff value for TG/TSH was determined as 29.67.…”

“…In addition, it has been shown that an increased serum TSH and thyroglobulin (TG) ratio is a more efficient marker in the diagnosis of thyroid cancer compared to TSH alone. [ 11 - 13 ]…”

“…In addition, it has been shown that an increased serum TSH and thyroglobulin (TG) ratio is a more efficient marker in the diagnosis of thyroid cancer compared to TSH alone. [11][12][13] The aim of this study was to determine diagnostic ratios for the prediction of DTC by examining patients' serum levels that are routinely checked at the follow-up appointments of patients with thyroid nodules.…”

Diagnostic, Theranostic and Prognostic Value of Thyroglobulin in Thyroid Cancer

“…Various attempts have been made to improve the specificity of the Tg measurement by linking it with other diagnostic param-eters. For example, the value of a TSH/Tg ratio or Tg/TSH ratio was examined [80][81][82][83]. Ultimately, however, such ratio cannot significantly improve the accuracy of diagnosing a DTC.…”