Treatment of multinodular goiter In the past iodine supplementation seems to be an adequate approach because goiter development is associated with mild iodine deficiency in many countries worldwide. The effect of iodine once a multinodular goiter has developed a limited value in reducting the MNG. A major problem of iodine supplementation is the risk for inducing subclinical / clinical hyperthyroidism (Jod-Basedow). Therefore aside from a few European Countries iodine is no longer used alone or associated with L-T4 to treat thyroid enlargement (24). This leaves in essence three modalities of therapy: (1). L-T4 suppressive therapy (2). Radioiodine (¹³¹I) alone or preceded by rhTSH (3). Surgery L-T4 suppressive therapy L-T4 suppressive therapy is used extensively both in Europe, USA and Latin America, according to their respective surveys. A beneficial effect of L-T4 has been demonstrated in diffuse goiters in many controlled trials (106-112). A goiter reduction of 20-40% can be expected in 3-6 months of therapy, the goiter returning to the pre-treatment size after L-T4 withdrawal. The efficacy of L-T4 is shown to depend on the degree of TSH suppression. When it comes to the nontoxic MNG there are five controlled studies in which sonography was used for objective size monitoring. Berghout et al (113) in a randomized double-blind trial showed that the goiter volume was reduced by 15% (9 months of L-T4 therapy). In the placebo group the goiter continued to increase in size by more than 20% in the 9 months period. The goiter volume returned to baseline values after discontinuation of the therapy. Lima et al (109) studied 62 patients with nodular goiter. Thirty per cent of patients were regarded as responders (reduction 50% of the initial volume). In the control group 87% showed no change or an increase in goiter size. Wesche et al (110) compared L-T4 with ¹³¹I therapy in a randomized trial. The median reduction of goiter volume in the radioiodine treated group was 38-44% whereas only 7% of the L-T4 treated patients had a significant goiter reduction. Papini et al (111) treated 83 goitrous patients (nodular goiter) with suppressive doses of L-T4 comparing the results with a control group. The L-T4 therapy was extended for 5 years. There was a decrease in nodular size in the L-T4 treated group and a mean volume increase in the control group. After 5 years sonograms detected 28.5% new nodules in the control group but only 7.5% in the L-T4 treated group. In conclusion long term TSH suppression induced volume reduction in a subgroup of thyroid nodules but effectively prevented the appearance of new nodules. Zelmanovitz et al (112) studied 42 women with a single colloid nodule. Twenty one patients were treated with 2.7µg/kg of L-T4 for one year. Six of the 21 treated patients had a 50% reduction of the nodule volume as evaluated by sonography as compared to only 2 (out of 24 patients) that received placebo. They concluded that L-T4 therapy is associated with 17% of reduction of a single colloid nodule and may inhibit growth in other patients. They also conducted a meta-analysis of 6 prospective controlled trials and concluded that four of seven studies favors treatment with L-T4. The treatment