GOITER - FROM THE EPIPHENOMENON OF IODINE DEFICIENCY TO THE TRUE TUMOR

Thirty years ago, iodine deficiency was highly prevalent in Switzerlan d and, consequently, few people doubted that shortage of this element fully accounted for the very high incidence of nodular goiters. Most r esearch efforts were aimed at unraveling the mechanisms that allowed t he thyroid to maintain adequate hormone production - at the expense of goiter formation - despite insufficient iodine supply. In 1982 iodine deficiency was eradicated in this country, a remarkable achievement o f preventive medicine. Although the incidence of goiter dramatically d ecreased thereafter, this thyroid disease has remained and still is a common problem. Only now has it become clear that factors other than o r in addition to iodine shortage must be operative in goitrogenesis an d that classical features, such as the tremendous functional and morph ological heterogeneity of goitrous tissue, and, in particular, the gro wth of nodules, must result from causes and mechanisms that are common to the pathological growth of other tissues too. Subsequently, the th yroid has become a rewarding source of information about cellular and more recently - molecular events that accompany and might possibly cau se pathological growth. Today, thyroid nodules are considered to be tr ue monoclonal and polyclonal tumors. Hence, we no longer wonder why er adication of iodine shortage cannot totally prevent or reverse goiter growth. - While modern molecular biology unravels - at an amazing pace - the mechanisms that cause heterogeneity between individuals of a si ngle species, goitrogenesis offers a unique opportunity to go one step beyond, which is the inborn and acquired heterogeneity between the in dividual cells of the same tissue. For instance, a monoclonal goiter a denoma allows to take a glimpse at the mechanisms which create heterog eneity among the progeny of one single cell. The author of this invite d minireview has been offered the opportunity to closely follow, durin g 30 years of interwoven clinical and basic research, the evolution of the concept of goitrogenesis, which has turned goiter growth from pur e adaptive hyperplasia into true tumor formation.