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Peer-reviewedCC BY 4.0Journal of Physiological Anthropology

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

  • Yuji Shimizu1,2
  • Nagisa Sasaki2
  • Asuka Oyama2
  • Yuko Noguchi3
  • Mutsumi Matsuu-Matsuyama4
  • Koichiro Hamada1
  • Shin-Ya Kawashiri3,5
  • Hirotomo Yamanashi1,5
  • Seiko Nakamichi1,6
  • Yasuhiro Nagata3,5
  • Takahiro Maeda1,5
  • Naomi Hayashida4,5
6 affiliations
  1. 1Department of General Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501 Japan
  2. 2Epidemiology Section, Division of Public Health, Osaka Institute of Public Health, Osaka, 537-0025 Japan
  3. 3Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8523 Japan
  4. 4Department of Health Society and Statistics, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, 852-8523 Japan
  5. 5Leading Medical Research Core Unit, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8523 Japan
  6. 6Nagasaki University Health Center, Nagasaki, 852-8521 Japan
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{shimizu2026potential,
  title = {{The potential modulating role of thyroid cysts on the association between anti–thyroid peroxidase antibodies and subclinical hypothyroidism}},
  author = {Yuji Shimizu and Nagisa Sasaki and Asuka Oyama and Yuko Noguchi and Mutsumi Matsuu-Matsuyama and Koichiro Hamada and Shin-Ya Kawashiri and Hirotomo Yamanashi and Seiko Nakamichi and Yasuhiro Nagata and Takahiro Maeda and Naomi Hayashida},
  journal = {Journal of Physiological Anthropology},
  year = {2026},
  month = aug,
  doi = {10.1186/s40101-026-00443-9},
  url = {https://doi.org/10.1186/s40101-026-00443-9},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The potential modulating role of thyroid cysts on the association between anti–thyroid peroxidase antibodies and subclinical hypothyroidism
AU  - Yuji Shimizu
AU  - Nagisa Sasaki
AU  - Asuka Oyama
AU  - Yuko Noguchi
AU  - Mutsumi Matsuu-Matsuyama
AU  - Koichiro Hamada
AU  - Shin-Ya Kawashiri
AU  - Hirotomo Yamanashi
AU  - Seiko Nakamichi
AU  - Yasuhiro Nagata
AU  - Takahiro Maeda
AU  - Naomi Hayashida
PY  - 2026
DA  - 2026/08/08
JO  - Journal of Physiological Anthropology
DO  - 10.1186/s40101-026-00443-9
UR  - https://doi.org/10.1186/s40101-026-00443-9
AB  - 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.
SN  - 1880-6791
SN  - 1880-6805
ER  -