The effect of intrathyroidal versus intraperitoneal bevacizumab on thyroid volume and vasculature flow in a rat model

Aaron Smith, Vikrum Thimmappa, John D. Boughter Jr, Christopher Vanison, Courtney B. Shires, Merry Sebelik


Background: Several clinical conditions increase thyroid gland vascularity, impacting surgical blood loss. Bevacizumab has been observed to reduce thyroid function, possibly through its effect on gland angiogenesis. This study aimed to determine if bevacizumab has any effect on thyroid vascularity as measured by gland volume and superior thyroid artery (STA) flow velocity in the normal rat thyroid.
Methods: Sixteen adult female Sprague-Dawley rats were placed under general anesthesia to measure baseline thyroid gland characteristics. A Vevo 2100 high-frequency ultrasound with 40 mHz transducer was used to obtain STA flow measurements and thyroid gland dimensions. Four rats served as controls. Six rats received intrathyroidal (IT) injections and 6 received intraperitoneal (IP) injections of bevacizumab (4–5 mg/kg). After two weeks ultrasound measurements were repeated.
Results: Pretreatment animals displayed similar thyroid volume and vascularity. Thyroid volume decreased (62.583 vs. 42.161, P=0.004) after IP administration of bevacizumab, and blood flow measurements did not change [peak velocity 75.896 vs. 76.7, P=0.96, average velocity 45.748 vs. 43.867, P=0.88, or resistivity index (RI) 30.345 vs. 25.32, P=0.60]. IT bevacizumab did not change thyroid volume (55.229 vs. 58.16, P=0.64). The average peak (73.191 vs. 100.589 cm/s, P=0.03) and mean (45.047 vs. 62.843 m/s, P=0.03) velocities were increased, but did not differ in the RI (0.619 vs. 0.632, P=0.82). No differences were noted on VEGF or CD 31 immunohistochemical analysis.
Conclusions: Single systemic administration of bevacizumab appears to decrease thyroid volume without an effect on STA flow, VEGF or CD31 staining. These preliminary findings support further study of pharmacologic intervention in thyroid conditions characterized by increased angiogenesis and vascularity, such as iodine deficiency, Graves disease, and hypothyroidism.