Research Papers:

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

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

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Oncotarget. 2018; 9:3406-3416. https://doi.org/10.18632/oncotarget.23281

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Guangjian Zhang1, Rui Gao2, Yuanbo Wang2, Yan Liu2, Juan Li2, Xi Jia2, Yiqian Liang2 and Aimin Yang2

1Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

2Department of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

Correspondence to:

Aimin Yang, email: [email protected]

Keywords: differentiated thyroid cancer; TENIS syndrome; integrin αvβ3; thymus; RGD peptide

Received: July 11, 2017     Accepted: November 17, 2017     Published: December 15, 2017


Aims: To 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.

Methods: A 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.

Results: Enlarged 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.

Conclusions: The 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.

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