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Background:Nontoxic nodular goiter (NTNG) is common in endemic goiter regions. Thyroxine (T4) is often used to treat NTNG. There is little information regarding T4 treatment in regions that have recently become iodine sufficient. We studied the effect of T4 treatment on thyroid function tests in southwestern Greece (SWG), a recently iodine-sufficient area.Methods:We studied 827 residents of SWG (group A) to determine goiter prevalence, thyroid function, and urinary iodine concentration (UIC). Group B: 385 consecutive patients with thyroid dysfunction. Of these, 89 had NTNG and followed for 10 years on T4 treatment, and 296 had hyperthyroidism. Group C: 29 patients with NTNG, treated with triiodothyronine (T3) 50 μg/day and followed for 6 months. Measurements included serum T4 and 24-hour radioactive iodine uptake (RAIU) before and at the end of T3 administration.Results:The median UIC in group A was 114 μg/L. In group B (89 patients), the incidence of newly diagnosed hyperthyroidism was 5–7 per year with a cumulative percentage of 33 at the 10th year. The initial thyrotropin (TSH) was lower (0.78 ± 0.51 mIU/L) in those who developed thyrotoxicosis compared to those who remained euthyroid (1.17 ± 0.74 mIU/L) (p< 0.05). In 296 thyrotoxic patients, the incidence of autoimmune hyperthyroidism and toxic multi-nodular goiter (TMNG) was similar. In group C, 10/29 patients remained euthyroid and the 24-hour RAIU decreased by 49 during T3 treatment. Similarly, serum T4 decreased by 49. In the remaining patients who developed hyperthyroidism, 24-hour RAIU and T4 were decreased by 19 and 22, respectively.Conclusions:In SWG, a recently iodine-sufficient region, the risk of developing hyperthyroidism in patients with NTNG after administration of 100–150 μg T4 is relatively high in those whose serum TSH before T4 treatment is in the lower normal range. Therefore, T4 treatment should be avoided in these patients. [ABSTRACT FROM AUTHOR]