In order to establish whether thyroglobulin autoantibodies (TgAb) influence the metabolic clearance of thyroglobulin (Tg) in humans, serum Tg and TgAb were correlated shortly after radioiodine (131I) treatment.Samples were collected from 30 consecutive patients undergoing 131I activity for Graves' hyperthyroidism at the time of treatment and every 15 days thereafter, up to 90 days. Tg and TgAb were measured by immunometric assays (functional sensitivities: 0.1 ng/mL and 8 IU/mL).Tg was detectable in all patients at day 0. Tg concentrations rose from a mean of 33.2 ng/mL [confidence interval (CI) 17.8-61.0 ng/mL] at day 0 to a mean of 214.6 ng/mL [CI 116.9-393.4 ng/mL] at day 30 and then steadily decreased, reaching the lowest concentration at day 90 (M = 10.9 ng/mL [CI 5.5-20.9 ng/mL]). Compared to their levels at day 0 (M = 23.6 IU/mL [CI 10.5-52.9 IU/mL]), TgAb remained stable through day 15 and then gradually increased up to a mean of 116.6 IU/mL [CI 51.9-262.2 IU/mL] at day 90. Patients were then split into two groups according to their TgAb status at day 0: undetectable (<8 IU/mL; 9 patients) or detectable (≥8 IU/mL; 21 patients) TgAb. Compared to the other cohort, patients with detectable TgAb showed significantly lower Tg concentrations at day 0 (M = 20.3 ng/mL [CI 10.1-40.2 ng/mL] vs. M = 101.8 ng/mL [CI 36.6-279.8 ng/mL]), similar at day 15, lower levels at day 30 (M = 146.5 ng/mL [CI 74.3-287.8 ng/mL] vs. M = 514.8 ng/mL [CI 187.8-1407.9 ng/mL]), at day 45 (M = 87.5 ng/mL [CI 43.1-176.6 ng/mL] vs. M = 337.9 ng/mL [CI 120.1-947.0 ng/mL]), at day 60 (M = 61.6 ng/mL [CI 31.0-121.4 ng/mL] vs. M = 255.8 ng/mL [CI 79.0-823.8 ng/mL]), and at day 75 (M = 24.5 ng/mL [CI 11.9-49.2 ng/mL] vs. M = 249.5 ng/mL [CI 63.5-971.1 ng/mL]), and similar levels at day 90. Patients with detectable TgAb showed a lower (M = 182.5 ng/mL [CI 92.0-361.0 ng/mL] vs. M = 514.8 ng/mL [CI 187.8-1407.9 ng/mL]) and an earlier (day 15 vs. day 30) peak of Tg. The mean Tg concentration was lower in patients with detectable TgAb than in those with undetectable TgAb (area under the curve: 17,340 ± 16,481 ng/mL vs. 36,883 ± 44,625 ng/mL; p = 0.02).TgAb influence the changes in Tg concentrations observed immediately after 131I treatment, inducing lower levels and an earlier peak of Tg. These observations indicate that TgAb significantly influence the metabolic clearance of Tg, supporting the concept that their interference in the measurement of Tg is mainly due to an in vivo effect.