Association of thyroid peroxidase antibodies with thyroid nodules and differentiated thyroid cancer in Graves' disease: a retrospective cohort study.

Abstract

Objective: In Graves' disease (GD), thyroid nodules are the principal determinant of differentiated thyroidcaneer(DTC); however, the predictors of nodules and DTC remain uncertain. The role of thyroid peroxidase antibodies (TPOAb) in this context is controversial. Hence, this study aimed to determine whether TPOAb status is associated with thyroid nodules and DTC in GD and to compare the prevalence of DTC across subtypes of hyperthyroid disease.

Subjects and methods: We conducted a retrospective cohort study (September 2020-July 2023) including patients with GD (n = 577) and toxic nodular/multinodular goiter (TNG/ TMNG) (n = 216) who had available TPOAb measurements and thyroid ultrasonography. Within the GD cohort, multivariable logistic regression was used to assess associations of TPOAb titer with nodules and DTC.

Results: TPOAb positivity was more frequent in GD than in TNG/TMNG (60.4% vs. 7.4%, p < 0.001). Among GD patients, thyroid nodules were detected in 25.8% and were less frequent in TPOAb-positive patients compared with TPOAb-negative patients (8.3% vs. 52.6%, p < 0.001). Within GD, DTC was rare among those without nodular disease (0.93%) but substantially higher in nodular GD (14.1%, p < 0.001), exceeding the prevalence observed in TNG/TMNG (p = 0.009). TPOAb status further stratified DTC risk in GD: DTC was present in 1.15% of TPOAb-positive compared to 9.21% of TPOAb-negative patients (p < 0.001), with 84% of GD-associated DTCs arising in the TPOAb-negative subgroup. Regression analyses showed that TPOAb titer was independently associated with lower frequencies of both DTC and nodules in GD, whereas thyrotropin receptor antibodies levels showed no independent association.

Conclusion: In GD, our study showed that TPOAb positivity was strongly associated with lower prevalence of thyroid nodules and DTC, whereas TPOAb-negative patients constitute a clinically relevant, higher-risk subgroup.