Analysis of risk factors for hypothyroidism in initially euthyroid patients with positive thyroid autoantibodies: a...

Thyroid autoantibody positivity is a common immune marker and a major precursor of hypothyroidism. Currently, there is a lack of effective tools and risk stratification criteria for identifying individuals at risk of its progression to either overt or subclinical hypothyroidism.

To investigate the independent risk factors for future onset of hypothyroidism and determine an optimal anti-thyroid peroxidase antibody (TPOAb) cutoff for identifying high-risk individuals.

A multicenter retrospective cohort study was conducted. A total of 669 patients initially diagnosed with positive thyroid autoantibodies with positive thyroid autoantibodies (TPOAb and/or TgAb) in Nanjing from January 2018 to December 2024 were enrolled. Baseline demographic data, thyroid function parameters, and autoantibody levels were collected. The primary endpoint was progression to overt or subclinical hypothyroidism during follow-up. Cox proportional hazards regression models were used to identify independent risk factors. The optimal risk-stratification cutoff value for TPOAb was determined using the maximum selection method. Risk stratification performance was evaluated using the Akaike Information Criterion (AIC) and the concordance index (C-index).

During a median follow-up of 3.0 years, 155 patients progressed to overt or subclinical hypothyroidism. Multivariate Cox regression analysis revealed that age was a protective factor (18-45 years vs ≤18 years: HR = 0.36, 95% CI: 0.22-0.58, P < 0.001; ≥45 years vs ≤18 years: HR = 0.45, 95% CI: 0.26-0.80, P = 0.007). Baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4), and TPOAb levels were identified as independent risk factors (all P < 0.05). The optimal risk-stratification cutoff for TPOAb was 187 IU/mL. Risk stratification using this cutoff demonstrated a lower AIC value (811.05) and a higher C-index (0.700) compared to the model using the commonly used clinical cutoff of 60 IU/mL.

This study identifies that age, baseline TSH, FT4, and TPOAb levels are independent risk factors for the progression to hypothyroidism in patients with hypothyroidism onset in initially euthyroid patients with positive thyroid autoantibodies. A TPOAb cutoff of 187 IU/mL provides better risk discrimination and can be utilized for clinical identify high-risk patients and individualized monitoring.