Clinical Significance of Thyroid Autoantibodies in Differential Diagnosis and Predicting the Course of Programmed Cell Death Protein-1 Inhibitor-Induced Thyroid Dysfunction

Objective

Thyroid immune-related thyrotoxicosis is one of the most common adverse effects in patients treated with programmed cell death protein-1 (PD-1) inhibitors. We investigated the significance of levels of serum anti-thyroglobulin antibodies (TgAbs), anti-thyroid peroxidase antibodies (TPOAbs), and thyroid-stimulating hormone receptor antibodies (TRAbs) in the identification of anti-PD-1-induced thyroid thyrotoxicosis.

Methods

We divided 161 patients with thyroid dysfunction who received PD-1 inhibitors at our hospital between January 2022 and June 2024 into 3 groups: primary hypothyroidism group, primary hyperthyroidism group, and destructive thyroiditis group. The characteristics of the 3 groups were determined, and the positivity rates of serum TgAbs, TPOAbs, and TRAbs were assessed. An additional 42 patients diagnosed with Hashimoto’s thyroiditis were selected as the control group for PD-1 inhibition-induced destructive thyroiditis. Age, sex, and time of transition from thyrotoxicosis to hypothyroidism in the 2 groups were compared.

Results

In the primary hypothyroidism group, only 1 case was TPOAbs-positive (1/1%). In the destructive thyroiditis group, the positivity rate for TPOAbs or TgAbs was 92.9%, and TPOAbs and TgAbs were negative in the primary hyperthyroidism group. TRAbs were undetectable in all 3 groups. There were statistically significant differences in age, sex, and time from thyrotoxicosis to hypothyroidism in the PD-1 induced destructive thyroiditis and Hashimoto’s thyroiditis groups.

Conclusions

In patients with thyrotoxicosis caused by PD-1 inhibitors, serum TgAb, and TPOAb levels can be used to distinguish between primary hyperthyroidism and destructive thyroiditis. This study provides insights into novel treatment targets and effective management strategies for PD-1-induced thyrotoxicosis.