Hyperplastic thymus with increased angiogenesis is correlated with elevated serum thyroglobulin level in differentiated thyroid cancer patients with TENIS syndrome.

Guangjian Zhang,Yan Liu,Rui Gao,Xi Jia,Aimin Yang,Juan Li,Yiqian Liang,Yuanbo Wang

doi:10.18632/oncotarget.23281

Guangjian Zhang, Yan Liu + Show 6 more

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https://doi.org/10.18632/oncotarget.23281

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Abstract

AimsTo investigate the association between angiogenetic activity of hyperplastic thymus and serum thyroglobulin (Tg) level in differentiated thyroid carcinoma patients with thyroglobulin (Tg)-elevated Negative Iodine Scintigraphy (TENIS) Syndrome.MethodsA cohort of 30 consecutive patients who underwent total thyroidectomy followed by radioiodine ablation and had TENIS syndrome received integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2). The correlation of angiogenetic activity of the thymus and the serum Tg levels was evaluated in patients with enlarged thymus.ResultsEnlarged thymus was detected in 9 out of the 30 TENIS patients and all hyperplastic thymus showed an increased accumulation of the tracer (median tumor/background ratio: 2.8). Five of them had only mediastinal uptake and surgical removal of the mediastinal mass in one provided histopathologic evidence of thymic tissue. The other four were not assigned further treatment and were free of disease in the follow-up, though their stimulated Tg levels consistently increased. Four out of the 9 patients showed 99mTc-3PRGD2 uptake outside the mediastinum were assigned surgery followed by radioiodine treatment. Their stimulated Tg levels decreased after iodine ablation, but not drop back to normal. A significant linear correlation was observed between serum Tg levels and the degree of angiogenesis in the hyperplastic thymus.ConclusionsThe angiogenetic activity in hyperplastic thymus was related with the consistently elevated serum Tg levels in TENIS syndrome patients. Based on the existing literature and current data, we propose further intervention for patients with RGD uptake outside thymus, while close follow-up for patients with only mediastinal uptake.

Highlights

Differentiated thyroid cancer (DTC) accounts for 1% of all malignant tumors, and has shown a rapid rise in the past several years [1]
Total thyroidectomy followed by iodine-131 (131I) ablation is recommended for the initial treatment of DTC patients, with serial serum thyroglobulin (Tg) tests and imaging measurements as follow-up [2]
In 9 of 30 patients (30.0%), co-registered diagnostic computed tomography (CT) scan for 99mTc-3PRGD2 single photon emission computed tomography (SPECT)/CT revealed an enlarged thymus, a finding that was compatible with the 99mTc-3PRGD2 uptake observed on SPECT/CT images, i.e. all enlarged thymus showed an increased accumulation of the tracer (Figure 1)

Summary

Introduction

Differentiated thyroid cancer (DTC) accounts for 1% of all malignant tumors, and has shown a rapid rise in the past several years [1]. Total thyroidectomy followed by iodine-131 (131I) ablation is recommended for the initial treatment of DTC patients, with serial serum thyroglobulin (Tg) tests and imaging measurements as follow-up [2]. A situation as there is no radiologically or clinically evident disease, but Tg levels remain detectable or even significantly elevated (TENIS syndrome) is common in clinical practice [3]. The probable explanation for such condition might be that lesion is too small to image but large enough to secret Tg [4]. An empirical 131I ablation or surgery was suggested for TENIS syndrome patients with Tg level of more than 10 μg/L [5]. The recognition of physiological Tg secretion is critical for patients with the TENIS syndrome to avoid unnecessary treatments

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