For some, chronic lymphocytic thyroiditis (Hashimoto thyroiditis) is an important risk factor for differentiated thyroid cancer (DTC). Surgical cohort studies even suggested a potential role for thyroid peroxidase antibodies (TPO-Abs) on that risk. Our clinical observations argued against that possibility. We designed the present study to evaluate the relationship of TPO-Abs and DTC in a large patient population. We recruited individuals who underwent thyroidectomies at 4 different clinical sites (USA: 1 clinic, 2000-2013, and Greece: 3 clinics, 2007-2021). We gathered data on TPO-Abs titers measured with commercially available chemiluminescence immunoassays, and reviewed patients' data including surgical pathology. TPO-Abs of 34 IU/mL or greater was deemed positive (TPO+) and TPO-Abs less than 34 IU/mL was deemed negative (TPO-). Odds ratios (OR) for DTC were calculated with the Fisher exact test and P less than .05 was deemed significant. We reviewed data from 8461 consecutive thyroid surgery cases. TPO-Abs titers were available for 1635 individuals: DTC n = 716 (43.8%), benign pathology n = 919 (56.2%), TPO+ n = 540 (33.0%), and TPO- n = 1095 (67.0%). DTC was found at a lower frequency in TPO+ (198/540, 36.7%) compared to TPO- (518/1095, 47.3%) patients, OR 0.64 (0.52-0.80; P < .0001). Rising TPO-Abs titers conferred protection against DTC in a linear fashion: TPO-Abs less than 10 IU/mL: 59.3%, TPO-Abs less than 34 IU/mL: 47.4%, TPO-Abs 34 to 100 IU/mL: 42.6%, TPO-Abs 100 to 500 IU/mL: 32.0%, TPO-Abs greater than 1000 IU/mL: 19.4%; P less than .0001. Higher TPO-Ab titers appear protective against DTC in our large multicenter cohort of patients who underwent thyroidectomies. Rising preoperative TPO-Abs titers conferred linearly increasing protection against DTC.
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