Questions and answers on the epidemiology and etiology of goiter

Goitre defines any enlargement of the thyroid independent of its cause. Worldwide iodine deficiency is the single most common cause of a goitre. However, before iodine deficiency is established, other thyroid diseases need to be ruled out. Very rarely increased production of TSH (secondary hyperthyroidism) or of hormones with TSH activity (e.g. hCG producing tumours), inborn errors of iodine metabolism, and defects of the thyroid hormone receptor (thyroid hormone resistance) are the cause of a goitre. Furthermore, malignancy of the thyroid and autoimmune disease (e.g. Grave's disease) may lead to a thyroid enlargement. Still, worldwide more than 90% of the 200 million patients with goitre suffer from iodine deficiency. In Germany, as in only few other European countries which lack any nation-wide prophylactic iodine supplementation, goitre is endemic with a prevalence of about 25%. The classical concept on the mechanism of iodine deficiency induced goitre is based on decreased thyroid hormone synthesis in the presence of iodine depletion, which leads to increased production of TSH, stimulating thyroidal growth. Recent in vitro findings using thyroid cell cultures expand this concept by demonstrating that TSH regulates the differentiation and function of thyroid cells and may induce hyperplasia, but not cell proliferation. In contrast to TSH, the locally produced growth factors IGF I (insulin-like growth factor I) and EGF (epidermal growth factor) stimulate thyroid cell proliferation. Intrathyroidal iodine antagonises the effects of IGF I and EGF and simultaneously stimulates transforming growth factor beta (TGF-beta), which inhibits thyroid cell proliferation. Thus, intrathyroidal iodine appears to regulate thyroidal growth by controlling proliferation stimulating (IGF I, EGF) and proliferation inhibiting (TGF-beta) growth factors. Though these new insights fill several gaps of the classical concept on the pathogenesis of endemic goitre, open questions remain.