Long-term natural history of thyroid peroxidase antibodies in a population-based cohort: Findings from 18 years of follow-up in Tehran Thyroid Study (TTS)

Background: Thyroid peroxidase antibody (TPOAb) is considered a highly sensitive marker of autoimmune thyroid diseases (AITD). Limited longitudinal data exist regarding its long-term natural history in the general population. This study aimed to assess risk factors for TPOAb positivity and its 18-year prevalence, incidence, trajectories, and projected prevalence for the year 2030 in a population-based cohort. Methods: A total of 5,438 adults were recruited at first visit (1999-2002) and followed across four subsequent visits up to 2018 in the iodine-sufficient population-based Tehran Thyroid Study (TTS). The age- and sex-standardized prevalence of TPOAb positivity was calculated, and the projected prevalence in 2030 was estimated using Poisson Generalized Linear Mixed Model (Poisson GLMM). Longitudinal trajectories of TPOAb were identified using latent class growth mixture model (LCGMM). Cox proportional hazards models were used to examine associations between potential risk factors and TPOAb positivity. Results: The prevalence increased progressively from 11.7% at the first visit (1999-2002) to 16.3% at the fifth visit (2015-2018), and is projected to reach 21.04% in 2030. Four distinct TPOAb trajectories were identified: Low-stable (81.4%), Low-increasing (2.9%), High-decreasing (2.4%), and High-stable (13.3%). The overall incidence rate of TPOAb positivity was 5.6 per 1,000 person-years, higher among women and individuals aged <40 years. In multivariable analysis, female sex (Hazard Ratio (HR) = 1.61; 95% CI: 1.15-2.27) and elevated TSH ≥5 mU/L (HR = 2.69; 95% CI: 1.57-4.63) were significant positive predictors of TPOAb positivity, while age between 40 and 60 years was inversely associated with incident TPOAb positivity (HR = 0.71; 95% CI: 0.55-0.90). Conclusions: This is the first and longest study worldwide that demonstrated a persistent rise in TPOAb positivity across five repeated measurements in an iodine-sufficient population, driven by female sex, age <40, and TSH ≥5 mU/L, which is projected to reach 21.04% in 2030. Trajectory patterns of TPOAb showed that the majority of participants had consistently low-stable levels of TPOAb.