No 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.

Differentiated thyroid cancer (DTC) represents the vast majority of all thyroid cancers, with the papillary variant being the most common. According to the previous 2009 American Thyroid Association (ATA) guidelines, papillary thyroid microcarcinoma (PTMC; ≤1 cm in diameter) exhibiting cervical lymph node metastasis corresponded to an intermediate-risk group for recurrence or metastasis. However, the latest 2015 ATA guidelines advocate that a patient with PTMC is low-risk if there are ≤5 regional node micrometastases. This means that therapeutic radioactive iodine (RAI) is not required. The current study reports a rare case of a patient who underwent total thyroidectomy due to multi-nodular goiter where the pathologic specimen exhibited two PTMC foci in regional lymph nodes, but no primary cancer was identified in the thyroid despite thorough examination of the thyroid parenchyma. The etiology of such results is unknown and it was hypothesized that it may be the consequence of insufficient pathologic examination or due to the regression of a primary PTMC in the thyroid. Moreover, the risk-stratification of cases with intra-lymph node PTMC without any evidence of primary cancer in the thyroid is not considered in the ATA recommendations. The aim of the current report was to elucidate the risk-stratification of this rare occurrence and to reconsider the possible etiologies. By extrapolating the latest ATA recommendations concerning a patient with a known primary PTMC and ≤5 metastatic micro-foci (thus the only difference between cases being the absence of a primary tumor), it was concluded that the patient should be considered low-risk. As a consequence, RAI therapy should be deemed as unnecessary despite the presence of lymph node microfoci. Moreover, it was proposed that cervical lymph node PTMC with no evidence of a primary tumor in the thyroid could be the consequence of normal thyroid tissue micro-deposit progression to cancer within the lymph node, which is a rare benign entity.