By combining data from studies of multinodular non-toxic goitre (MNTG) with data from rat models of goitre induction and in vitro models, a map of the growth factors involved in goitrogenesis has been constructed. We have addressed the roles of the insulin-like growth factors, transforming growth factors, fibroblast growth factors, endothelins, etc. We hypothesise that an imbalance in the interactions between the various growth factor axes exists in MNTG which favours cell replication. Thyrotrophin, although not significantly elevated in MNTG, exerts critical effects through interactions with autocrine and paracrine factors and their receptors. Expansion of the thyroidal vascular bed through angiogenesis is closely co-ordinated with follicular cell expansion and folliculoneogenesis, and while the integrated paracrine actions of fibroblast growth factors, vascular endothelial growth factor and endothelin probably play central roles, additional, as yet elusive, factors are probably involved. The combination of in vitro and in vivo approaches, designed to address specific questions, will undoubtedly continue to prove invaluable in dissecting further the complex interactions that exist between these growth factors, their binding proteins and receptors in goitrogenesis.

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