Thyroid growth immunoglobulins in large multinodular endemic goiters: effect of iodized oil

Iodized oil (IO) was administered to 10 goitrous patients recently emigrated to São Paulo (SP) from iodine deficiency areas and to 42 goitrous patients from 2 Brazilian chronic iodine deficiency regions, Loreto and Luziania (L). Thyroid growth-promoting immunoglobulin G (IgG) thyroid-stimulating antibody, serum thyroglobulin (Tg), TSH, and thyroid hormones were measured before and 1 yr after IO administration. In all patients there was a remarkable reduction of gland mass associated with a significant decrease (P less than 0.01) in both basal serum Tg and peak Tg levels after bovine TSH administration. The mean percent Tg increase after bovine TSH treatment was reduced to 82% above basal levels compared with 224% before IO. Mean serum TSH levels, elevated only in the L group [7.3 +/- 11 (+/- SD) microU/ml] decreased to the normal range after IO (2.5 +/- 2.1 microU/ml). Serum T3 and T4 concentrations did not change greatly. Tests for microsomal antibodies were negative before and after IO. IgG concentrates of serum obtained before and after IO were tested for their ability to stimulate incorporation of [3H]thymidine into DNA or to increase intracellular generation of cAMP in FRTL-5 cells. Thymidine incorporation activity was found in 8 of 10 patients from SP [316 +/- 37% (+/- SEM); range, 140-480%] and 25 of 42 patients in the L group (mean, 206 +/- 14; range, 120-500%) before IO. Stimulation of thymidine incorporation reflected true growth-promoting activity, as confirmed by experiments measuring cell number, was not accounted for by TSH in the preparation, and reflected IgG action because it was abolished by absorption with antihuman IgG. IgG from only 1 patient in group SP and 4 patients in group L stimulated intracellular production of cAMP in FRTL-5 cells. All patients except 1 in both groups had no IgG stimulation (less than 120%) of growth-promoting activity 1 yr after IO treatment. There was a significant positive correlation between thyroid growth-promoting activity and serum Tg concentrations (r = 0.58; P less than 0.001), but no significant correlation was found with other parameters (TSH, T4, and T3). We conclude that growth-promoting IgGs lacking ability to stimulate cAMP production may play a role in the large multinodular goiters due to chronic iodine deficiency.