Angiogenesis, the formation of new blood vessels from existing vessels, has been recognized as playing an important role in the pathophysiology of many benign and malignant diseases (1,2). This chapter focuses on the role of the endothelium in the thyroid gland and explores the advances that have been made in our understanding of how the process of angiogenesis is involved in the pathophysiology of benign and malignant diseases of this gland.

HISTORY OF ENDOTHELIAL BIOLOGY IN THE THYROID

The structure and function of the thyroid gland has been the intense focus of study by physiologists, anatomists, surgeons, and basic scientists. Most attention has focused on the thyroid follicular cell, one of the most thoroughly studied cells in the human body. By comparison, the thyroid endothelium has received little attention. In the mid 1970s, there was increasing recognition that the endothelium of endocrine organs, including the thyroid, played an important role in homeostasis. At first, microscopy was used to study the structural detail of the fenestrated endothelium present in normal rat thyroid (3) as well as benign and malignant human thyroid tissue (4). The importance of angiogenesis in the progression of malignant disease was recognized during the early 1970s, with the realization by Folkman and colleagues that, for malignant tumor growth to progress beyond approximately 2 mm in diameter, the development of a vascular supply must occur (5). The role of endothelial cell (EC) proliferation in thyroid disorders was appreciated as early as 1978, with work performed by Wollman and colleagues (6).