The potential modulating role of thyroid cysts on the association between anti–thyroid peroxidase antibodies and subclinical hypothyroidism

Background In our previous study, the absence of thyroid cysts was identified as an indicator of thyroid functional strain associated with thyroid peroxidase antibody (TPO-Ab) positivity. In individuals under this continuous functional load, higher levels of thyroid-stimulating hormone are required to maintain serum thyroid hormone concentrations within the normal range, potentially leading to subclinical hypothyroidism (SCH). However, no study has examined whether the association between TPO-Ab positivity and SCH differs according to thyroid cyst status. Method We conducted a cross-sectional study of 1432 euthyroid Japanese participants whose free triiodothyronine (T3) and free thyroxine levels were within normal ranges. Thyroid cysts were defined as cystic lesions with a maximum diameter ≥ 2.0 mm and no solid components. Results Among the study population, 964 participants had no thyroid cysts, 267 were TPO-Ab positive, and 80 had SCH. A significant positive association between TPO-Ab positivity and SCH was observed only in participants without thyroid cysts. After adjustment for potential confounders—including sex, age, free T3, body mass index, atherosclerosis, and hypertension—the adjusted odds ratios (95% confidence intervals) were 0.27 (0.04, 2.02) and 2.10 (1.17, 3.77) for participants with and without thyroid cysts, respectively. Conclusion Among participants without thyroid cysts, TPO-Ab positivity was significantly associated with SCH, whereas no significant association was observed among those with thyroid cysts likely due to the small sample size. Reflecting a significant interaction between these factors, thyroid cyst status may modulate the association between TPO-Ab positivity and SCH, although further large-scale investigation is warranted.