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Increased Concentration of Vascular Endothelial Growth Factor/Vascular Permeability Factor in Cyst Fluid of Enlarging and Recurrent Thyroid Nodules¹

Department of Medicine(K.S., Me.M., N.O., H.D.) and Department of Surgery (K.Y., T.O.), Institute of Clinical Endocrinology, Tokyo Women’s Medical College; Second Department of Pathology (T.K.), Tokyo Women’s Medical College, Shinjuku-ku, Tokyo 162; and Mitsubishi-Kagaku Biochemical Laboratories (T.Y., Ma.M.) Itabashi-ku, Tokyo 111, Japan

Address all correspondence and requests for reprints to: Kanji Sato, Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women’s Medical College, Kawada-cho 8–1, Shinjuku-ku, Tokyo 162, Japan.

Human thyrocytes produce vascular endothelial growth factor (VEGF), a potent angiogenic factor, also known as vascular permeability factor (VPF), which increases vascular permeability. Based on the assumption that VEGF/VPF is involved in fluid accumulation in thyroid cysts, we determined the VEGF/VPF concentration in cyst fluids of thyroid nodules from 79 patients. VEGF/VPF was found to be abundantly present in the cyst fluids (0.02–183 ng/mL). There was no significant difference of VEGF/VPF concentration in the cyst fluid obtained from thyroid adenoma or from adenomotous goiter with cystic degeneration. Immunoreactive VEGF/VPF in cyst fluid was eluted mainly at 45 kDa, and stimulated endothelial cell proliferation, which was partially blocked by anti-VEGF/VPF antibody. The VEGF/VPF concentration in the cyst fluid obtained from patients who required repeated aspiration or underwent surgical resection because of recurrent accumulation (84.8 ± 58.3 ng/mL, mean ± SD, n = 18) was significantly higher than that in the cysts that regressed or disappeared after a single aspiration (4.3 ± 4.4 ng/mL, n = 12, P < 0.001).

These in vitro and clinical findings suggest that VEGF/VPF is at least partly involved in the accumulation of cyst fluid in thyroid nodules, and that a high VEGF/VPF concentration predicts rapid accumulation of the cyst fluid, possibly necessitating interventional treatment.

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