Preoperative Measurement of Serum Thyroglobulin to Predict Malignancy in Thyroid Nodules: A Systematic Review

Abstract

Several articles have assessed the role of preoperative serum thyroglobulin (Tg) as predictor of malignancy of thyroid nodules, with particular focus on nodules with indeterminate cytology. However, the role of serum Tg as diagnostic marker remains unclear. The aim of the study was to perform a systematic review to add more evidence-based data on this topic. A comprehensive literature search was conducted to find relevant published articles on this topic. MeSH terms were: "thyroglobulin" and "predict*". In order to include only recent serum Tg assay methods, we analyzed the timeframe between 2001 and July 31(st), 2014. To expand our search, references of the retrieved articles were also screened. Thirteen studies, including 3,580 patients, were analyzed. Nine out of these studies reported data on thyroid nodules with prior indeterminate cytology. Preoperative serum Tg levels demonstrated suboptimal accuracy in discriminating malignant from benign nodules due to a significant overlap of values between these groups. However, most articles demonstrated a statistically significant difference in mean or median serum Tg between patients with cancer and benign lesions correlated to final histology. Furthermore, most studies reported Tg as independent predictor of malignancy. According to the most recent literature, the preoperative measurement of Tg alone fails to discriminate thyroid cancers from benign lesions. However, our data show that Tg is an independent predictor of malignancy; as a consequence, the presurgical determination of Tg should be considered in patients with thyroid nodules, especially when cytology is indeterminate.

Thyroid nodules with indeterminate cytology: prospective comparison between 18F-FDG-PET/CT, multiparametric neck ultrasonography, 99mTc-MIBI scintigraphy and histology

“…This is in agreement with what was reported by a recent metaanalysis (33), in which the preoperative Tg value was deemed to be an independent predictor of thyroid cancer and should be considered especially in the case of thyroid nodules with indeterminate cytology.…”

Active surveillance in papillary thyroid carcinoma: not easily accepted but possible in Latin America

“…However, none of them showed an increase in tumor diameter. Until now, no conclusive studies had been conducted on the prognostic value of basal serum thyroglobulin levels in tumor progression during active surveillance (35). In our cohort, 23% of the patients decided to undergo surgery despite no increase in tumor size, mostly due to anxiety stemming from the follow-up.…”

BRAF‐mutated carcinomas among thyroid nodules with prior indeterminate FNA report: a systematic review and meta‐analysis

“…Furthermore, the elevated costs of the BRAF test (about 400 Euros per patient, with variation according to the different methods of analysis) have to be taken into account. Additionally, clinical, ultrasonographic, scintigraphic and immunocytochemical parameters have been shown to be useful in stratifying the risk of malignancy among indeterminate nodules, and thyroid lobectomy can provide definitive diagnosis with a low rate of complications …”

“…In particular, a novel gene‐expression classifier analysing 167 genes achieved negative predictive value (NPV) of 95% in this context . Immunohistochemistry for Galectin‐3 and HBME‐1, as well as ultrasonographic and scintigraphic parameters, have also been used to detect or exclude malignancy in nodules with prior indeterminate FNA . In addition, other biopsy strategies were reported as accurate in this context, and core needle biopsy (CNB) has been recently described as a second‐line approach for indeterminate thyroid lesions …”