Study On Associations Of VEGF, IGF-I And BFGF With Intrathyroidal Angiogenesis And Thyroid Volumes In Patients With Grave's Disease

Objective: Grave's disease (GD) is a common autoimmune thyroid disease. Diffuse goiter accompanied by obvious hyperthyroidial toxic sympotoms, the increasement of intrathyroidal flow velocity, angiogenesis and lymphocyts infiltration are the charistaristic features of GD. The more the vasculars in the thyroid are and the more bigger the thyroid volumes are , the longer the medical treatment for GD is. It is very important to study the mechaniam of intrathyroidal angiogenesis and thyroid volumes. The mechanism of thyroid volumes and intrathyroidal angiogenesis is not known.During the thyroid disease, the actions of growth factors are attached great importance to. It is thought growth factors can regulate the growth, differentiation and function of the thyroid cells through endocrine, autocrine, paracrine ways. They take part in the process of thyroid disease.Vascular endothelial growth factor (VEGF) is one of the most important soluble angiogenic factors. It can increase the microvascular permeability and facilitate to the exudation of plasma fibrin which offers fibre network for the movement of many cells. It also can stimulate the proliferation of endothelial cells and make it easy for endothelial cells to move. All are favorable for vascular formation. Insulin-like growth factor-â…  (IGF-â… ) has the functions of acceleratingproliferation, differention and metablism of many cells, such as endothelial cells and smmoth muscle cells, basic Fibroblast growth factor(bFGF),a growth factor, can promote cells' proliferation, differention, and livability and has close relationship to tumor, embryo development, denature and vascular abnormity. VEGF, IGF-I and bFGF are attached great importance in biology and many subjects.There are few reports about the association of growth factors and intrathyroidal angiogenesis and thyroid volumes at home and abroad. We aimed to measure change of serum VEGF, IGF-I level and VEGF, IGF-I, bFGF expression in thyroid tissues of patients with GD. We also aimed to study the relations between VEGF, IGF-I, bFGF and intrathyroidal angiogenesis and the relation between IGF-I and thyroid volumes in patients with GD.Methods.- The serum VEGF and IGF-I levels were measured by ELISA method in patients with GD (before and after treatment) and healthy subjects. Flow velocity of thyroid superartery (STA-FV), intrathyroidal microvessel density index (T-MVDI) and thyroid volumes of patients and healthy subjects were examined by colour Doppler ultrasonography. The measurement of STA-FV: determine the flow velocity of thyroid superartery of both sides of patients and healthy subjects and average them. The measurement of T-MVDI: under the conditions of stable color plus, flow velocity capacity and filter wave, determine the image of vascular area(VA) and thyroid area(TA) in both sides of patients and healthy subjects three times and then average the ratio of VA to TA. The measuremant of thyroid volumes: survey the lengthy, width, thickness of the right side, left side and gorge of the thyroid of patients and healthy subjects. The total thyroid volumes were the sum of the volume of the right side, the left side and gorge of thyroid. The protein expression of VEGF, IGF-I and bFGF was studied by immunohistochemistry (IHC) in GD thyroid tissues and normal thyroid tissues. The mRNA expression of VEGF and IGF-I was also studied by in situ hybridyzation(ISH). Microvessel density (MVD) in GD thyroid tissues wascounted by endothelial cells immunostained by anti-CD34 antibody which is the special antibody to bind with endothelial cells.Results: The serum VEGF, IGF-I , FT3, FT4 levels, STA-FV , T-MVDI and thyroid volumes of patients with GD were higher than those in healthy subjects(P<0.01) and were decreased after treatment ( P<0.05, 0.01, 0.01, 0.01,0.01,0.01,0.01 respectively). The serum VEGF, IGF-I level, STA-FV , T-MVDI and thyroid volumes of patients after treatment were still higher than those in healthy subjects(/3<0.05, 0.01, 0.01, 0.01, 0.01, respectively ). The FT3, FT4 level in patients after treatment showed no significant difference compared with healthy subjects.There were positive correlations between serum VEGF level and STA-FV, T-MVDI in patients with GD respectively( r=0.66, 0.71; P<0.01 ). There were also positive correlations between serum IGF-I level and STA-FV, T -MVDI in patients respectively 0=0.52, 0.49; P<0.0\ ) . Serum VEGF level positively correlated with serum IGF-I level in patients(r=0.43, P<0.01). There were no correlations between serum FT3 x FT4 level and serum VEGF, IGF-I level, STA-FV and T-MVDI. The protein expression of VEGF, IGF-I and bFGF in thyroid tissues of GD showed stronger staining compared with normal thyroid tissues by IHC (/><0.01) . The mRNA expression of VEGF and IGF-I in GD thyroid tissues was also higher than that in normal thyroid tissues by ISH (/><0.01,0.05 respectively). The protein expression VEGF, IGF-I and bFGF positively correlated with MVD in GD thyroid tissues(r=0.73,0.54;0.49 respectively; ?<0.01). VEGF expression was associated with IGF-I, bFGF expression in GD thyroid tissues (P<0.05). There was no correlation between IGF-I and bFGF expression in GD thyroid tissues.There was also a positive correlation between serum IGF-I level and thyroid volumes in patients with GD ( r=0.57, P<0.01 ) . The mRNA expression of IGF-I was positively associated with thyroid volumes in patients with GD before surgery ( r=0.63, P<0.01 ) .Conclusions : Our study suggest that VEGF, IGF-I and bFGF haverelationships with intrathyroidal angiogenesis in patients with GD. IGF-I was also associated with thyroid volumes in patients with GD.