A serum thyroid hormone metabolite test for molecular diagnostic evaluation of thyroid nodules
- 1Departments of Endocrinology and Metabolism, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University
Abstract
This was a cohort study of 1,663 subjects (1196 women, 467 men; median age 48 years, IQR 37-57) with thyroid nodules recruited from 2020 to 2025 in five tertiary medical centers. Cytological/histopathological diagnoses were established by an independent review committee and preoperative serum thyroid hormone metabolites (THMs) were tested using liquid chromatography tandem mass spectrometry. A diagnostic model on this serum THM test to distinguish between differentiated thyroid cancer (DTC) and benign thyroid nodule (BTN) was trained on 872 retrospective subjects (454 DTC and 418 BTN), followed, prospectively, by model validation on 392 subjects (195 DTC and 197 BTN) and a second validation on 399 subjects (300 DTC and 99 BTN). Following successful diagnostic model training, the model validation demonstrated a diagnostic specificity of 99.5% (196/197), sensitivity of 92.3% (180/195), positive predictive value (PPV) of 99.4%, negative predictive value (NPV) of 92.9%, and diagnostic accuracy of 95.9% (95% CI, 90.8 to 100.0%) for DTC. Combination of the two validation cohorts showed a diagnostic specificity of 99.7% (295/296), sensitivity of 92.1% (456/495), PPV of 99.8%, NPV of 88.3%, and diagnostic accuracy of 94.9% (95% CI, 91.5 to 98.0%) for DTC. The test on indeterminate Bethesda categories III-IV (139 DTC, 87 BTN) showed a diagnostic specificity of 100.0% (87/87), sensitivity of 93.5% (130/139), PPV of 100.0%, NPV 90.6% and diagnostic accuracy of 96.0% (95% CI, 89.2 to 100.0%) for DTC. This study develops a novel molecular blood test of serum THMs for preoperative diagnostic evaluation of thyroid nodules, which displays a high PPV and decent NPV with an excellent overall diagnostic accuracy for DTC.
Versions
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BibTeX
@misc{guo2026serum,
title = {{A serum thyroid hormone metabolite test for molecular diagnostic evaluation of thyroid nodules}},
author = {M. Guo and H. Geng and Q. Sun and H. Wan and P. Zhou and Y. Song and C. Zou and X. Zang and H. Xi and T. Liao and X. Liu and G. Peng and Y. Wang and M. Xing and J. Liang and THMs Group},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.26363992},
url = {https://www.medrxiv.org/content/10.64898/2026.09.25.26363992v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A serum thyroid hormone metabolite test for molecular diagnostic evaluation of thyroid nodules
AU - M. Guo
AU - H. Geng
AU - Q. Sun
AU - H. Wan
AU - P. Zhou
AU - Y. Song
AU - C. Zou
AU - X. Zang
AU - H. Xi
AU - T. Liao
AU - X. Liu
AU - G. Peng
AU - Y. Wang
AU - M. Xing
AU - J. Liang
AU - THMs Group
PY - 2026
DA - 2026/09/25
PB - medRxiv
DO - 10.64898/2026.09.25.26363992
UR - https://www.medrxiv.org/content/10.64898/2026.09.25.26363992v1
AB - This was a cohort study of 1,663 subjects (1196 women, 467 men; median age 48 years, IQR 37-57) with thyroid nodules recruited from 2020 to 2025 in five tertiary medical centers. Cytological/histopathological diagnoses were established by an independent review committee and preoperative serum thyroid hormone metabolites (THMs) were tested using liquid chromatography tandem mass spectrometry. A diagnostic model on this serum THM test to distinguish between differentiated thyroid cancer (DTC) and benign thyroid nodule (BTN) was trained on 872 retrospective subjects (454 DTC and 418 BTN), followed, prospectively, by model validation on 392 subjects (195 DTC and 197 BTN) and a second validation on 399 subjects (300 DTC and 99 BTN). Following successful diagnostic model training, the model validation demonstrated a diagnostic specificity of 99.5% (196/197), sensitivity of 92.3% (180/195), positive predictive value (PPV) of 99.4%, negative predictive value (NPV) of 92.9%, and diagnostic accuracy of 95.9% (95% CI, 90.8 to 100.0%) for DTC. Combination of the two validation cohorts showed a diagnostic specificity of 99.7% (295/296), sensitivity of 92.1% (456/495), PPV of 99.8%, NPV of 88.3%, and diagnostic accuracy of 94.9% (95% CI, 91.5 to 98.0%) for DTC. The test on indeterminate Bethesda categories III-IV (139 DTC, 87 BTN) showed a diagnostic specificity of 100.0% (87/87), sensitivity of 93.5% (130/139), PPV of 100.0%, NPV 90.6% and diagnostic accuracy of 96.0% (95% CI, 89.2 to 100.0%) for DTC. This study develops a novel molecular blood test of serum THMs for preoperative diagnostic evaluation of thyroid nodules, which displays a high PPV and decent NPV with an excellent overall diagnostic accuracy for DTC.
ER -