Differential Association of Serum TSH with Differentiated Thyroid Cancer Risk by Autoimmune Thyroiditis Status

<b>Background</b>: While elevated thyroid-stimulating hormone (TSH) is a known risk factor for differentiated thyroid cancer (DTC), it remains unclear whether autoimmune thyroiditis (AT) modifies this association. Clarifying this interaction is critical for personalized risk assessment and TSH suppression therapy. <b>Methods</b>: This study performed a retrospective analysis including 2425 participants who underwent thyroidectomy for thyroid nodules. Participants were categorized based on histological AT diagnosis and thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels. Multivariable logistic regression models were used to assess the association between thyroid parameters and DTC risk, stratified by AT and autoantibody status. <b>Results</b>: The prevalence of histological diagnosed AT, TgAb-positivity, and TPOAb-positivity among DTC patients was 31.58%, 13.68%, and 18.76%, respectively. An increase in one standard deviation in TSH, thyrotrophic thyroxine resistance index (TT4RI), and TSH index (TSHI) was associated with an elevated risk of DTC in euthyroid individuals without AT or positive thyroid autoantibodies. A positive and nonlinear association between TSH and DTC risk in euthyroid patients without AT was identified, with inflection points at TSH levels of 1.32 mIU/L. In subgroups characterized by concurrent AT, TgAb-positivity, or TPOAb-positivity, these thyroid parameters showed no statistically significant correlation with DTC risk. <b>Conclusions</b>: The association between TSH and DTC risk varies according to autoimmune thyroiditis status. These findings highlight the importance of considering thyroid autoimmunity in thyroid cancer risk assessment and warrant prospective evaluation to determine its potential implications for TSH suppressive therapy.