Role of TSHs and FT4 Levels in Thyroid Nodule Histopathology
DOI:
https://doi.org/10.22219/sm.Vol22.SMUMM1.44412Abstract
Thyroid nodules are a common clinical finding, although only a minority are malignant. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) have been investigated as potential biomarkers for predicting thyroid malignancy, yet previous studies have shown inconsistent results. This study aimed to analyse the association between TSHs and FT4 levels and histopathological outcomes in patients with thyroid nodules undergoing surgery. This analytical observational study used a cross-sectional design with retrospective medical record data from patients who underwent thyroid surgery at Wangaya Regional General Hospital during 2021–2025. Total sampling was applied based on the inclusion criteria, resulting in 121 patients with complete histopathological, TSHs, and FT4 data. The association between histopathological findings and hormone levels was analysed using chi-square test and logistic regression. Most patients were female (84.3%), and benign lesions predominated (71.1%). Higher TSHs levels were more frequent in borderline (66.7%) and malignant (56.3%) groups than in benign lesions (46.5%), but the association was not statistically significant (p=0.535). Lower FT4 levels were also more common in borderline (66.7%) and malignant groups (62.5%) than in benign lesions (48.8%), without significant association (p=0.367). TSHs and FT4 levels were not significantly associated with histopathological outcomes in patients undergoing thyroid surgery. These parameters should not be used as single predictors of thyroid malignancy.
Downloads
References
Alexander, E. K., Doherty, G. M., & Barletta, J. A. (2022). Management of thyroid nodules. The Lancet Diabetes & Endocrinology, 10(7), 540–548. https://doi.org/10.1016/S2213-8587(22)00139-5
Boucai, L., Zafereo, M., & Cabanillas, M. E. (2024). Thyroid Cancer. JAMA, 331(5), 425. https://doi.org/10.1001/jama.2023.26348
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229–263. https://doi.org/10.3322/caac.21834
Cappelli, C., Pirola, I., Gandossi, E., Rotondi, M., Lombardi, D., Casella, C., Marini, F., Saullo, M., Agosti, B., Di Lodovico, E., Chiovato, L., Ferlin, A., & Castellano, M. (2020). Could Serum TSH Levels Predict Malignancy in Euthyroid Patients Affected by Thyroid Nodules with Indeterminate Cytology? International Journal of Endocrinology, 2020, 1–6. https://doi.org/10.1155/2020/7543930
Durante, C., Hegedüs, L., Czarniecka, A., Paschke, R., Russ, G., Schmitt, F., Soares, P., Solymosi, T., & Papini, E. (2023). 2023 European Thyroid Association Clinical Practice Guidelines for thyroid nodule management. European Thyroid Journal, 12(5). https://doi.org/10.1530/ETJ-23-0067
Fan, X.-Y., You, W., Chen, Y., Nie, C.-C., Wang, X.-L., Lei, C., Song, J., & Luo, H.-L. (2024). A meta-analysis of the value of serum TSH concentration in the diagnosis of differentiated thyroid cancer in patients with thyroid nodules. Heliyon, 10(2), e24391. https://doi.org/10.1016/j.heliyon.2024.e24391
Forma, A., Kłodnicka, K., Pająk, W., Flieger, J., Teresińska, B., Januszewski, J., & Baj, J. (2025). Thyroid Cancer: Epidemiology, Classification, Risk Factors, Diagnostic and Prognostic Markers, and Current Treatment Strategies. International Journal of Molecular Sciences, 26(11), 5173. https://doi.org/10.3390/ijms26115173
Ghosh, R., Auh, S., Gubbi, S., Veeraraghavan, P., Cochran, C., Shobab, L., Urken, M. L., Burman, K. D., Wartofsky, L., & Klubo-Gwiezdzinska, J. (2025). Association of Free Thyroxine With Progression-Free Survival in Intermediate and High-Risk Differentiated Thyroid Cancer. The Journal of Clinical Endocrinology & Metabolism, 110(5), e1473–e1480. https://doi.org/10.1210/clinem/dgae537
Juweid, M. E., Rabadi, N. J., Tulchinsky, M., Aloqaily, M., Al-Momani, A., Arabiat, M., Abu Ain, G., Al Hawari, H., Al-Momani, M., Mismar, A., Abulaban, A., Taha, I., Alhouri, A., Zayed, A., Albsoul, N., & Al-Abbadi, M. A. (2021). Assessing potential impact of 2015 American Thyroid Association guidelines on community standard practice for I-131 treatment of low-risk differentiated thyroid cancer: case study of Jordan. Endocrine, 73(3), 633–640. https://doi.org/10.1007/s12020-021-02698-x
K. Alaraifi, A., Alessa, M., O. Hijazi, L., M. Alayed, A., & A. Alsalem, A. (2023). TSH level as a risk factor of thyroid malignancy for nodules in euthyroid patients. Acta Otorhinolaryngologica Italica, 43(3), 183–188. https://doi.org/10.14639/0392-100X-N2288
Kara, L., Siraz, U. G., Cicek, D., Sarikaya, E., Gok, E., Berber, U., Kendirci, M., Kurtoğlu, S., & Hatipoglu, N. (2026). The role of the FT3/FT4 ratio in predicting remission and relapse in pediatric Graves’ disease. European Journal of Pediatrics, 185(3), 172. https://doi.org/10.1007/s00431-026-06808-7
Larcher de Almeida, A. M., Delfim, R. L. C., Vidal, A. P. A., Chaves, M. C. d’Araujo C. M., Santiago, A. C. L., Gianotti, M. F., Gonçalves, M. D. da C., Vaisman, M., de Carvalho, D. P., & Teixeira, P. de F. dos S. (2021). Combining the American Thyroid Association’s Ultrasound Classification with Cytological Subcategorization Improves the Assessment of Malignancy Risk in Indeterminate Thyroid Nodules. Thyroid®, 31(6), 922–932. https://doi.org/10.1089/thy.2019.0575
Liu, J., Xu, T., Ma, L., & Chang, W. (2021). Signal Pathway of Estrogen and Estrogen Receptor in the Development of Thyroid Cancer. Frontiers in Oncology, 11. https://doi.org/10.3389/fonc.2021.593479
Mahendra Dewi, I. G. A. S., & Saraswati Seputra, D. P. G. (2022). Differences in Pre-Operative Mean Serum Concentration of Thyroid Stimulating Hormone (TSH) and Free Thyroxin (FT4) in Patients with Benign Thyroid Nodules and Thyroid Carcinoma at Sanglah General Hospital Denpasar. Indonesian Journal of Cancer, 16(1), 3. https://doi.org/10.33371/ijoc.v16i1.813
Sakajiri, R. K., Rahal, A., Francisco, M. J., Queiroz, M. R. G. de, Garcia, R. G., Martins, L. A. L., & Malerbi, D. A. C. (2022). Ultrasound classification of thyroid nodules: does size matter? Einstein (São Paulo), 20. https://doi.org/10.31744/einstein_journal/2022AO6747
Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA: A Cancer Journal for Clinicians, 70(1), 7–30. https://doi.org/10.3322/caac.21590
Singh, A., Ham, J., Po, J. W., Niles, N., Roberts, T., & Lee, C. S. (2021). The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy. Cells, 10(5), 1082. https://doi.org/10.3390/cells10051082
Su, A., Zhao, W., Wu, W., Wei, T., Ruan, M., Li, Z., & Zhu, J. (2020). The association of preoperative thyroid-stimulating hormone level and the risk of differentiated thyroid cancer in patients with thyroid nodules: A systematic review and meta-analysis. The American Journal of Surgery, 220(3), 634–641. https://doi.org/10.1016/j.amjsurg.2020.01.009
Trimboli, P., Curti, M., Colombo, A., Scappaticcio, L., & Leoncini, A. (2024). Combining TSH measurement with TIRADS assessment to further improve the detection of thyroid cancers. Minerva Endocrinology, 49(2). https://doi.org/10.23736/S2724-6507.24.04207-6
Vija, L. (2025). Special Issue “Molecular Biology of the Thyroid Cancer and Thyroid Dysfunctions.” International Journal of Molecular Sciences, 26(23), 11586. https://doi.org/10.3390/ijms262311586
Vinod, A., Ramachandran, R., Pillai, A. V., Padmanabhan, D. S., Ravindran, G. C., Babu, M. J. C., Jacob, P., & Nair, G. C. (2022). Serum TSH Level as a Simple Efficient Tool to Assess the Risk of Thyroid Malignancy in Euthyroid Patients with Indeterminate Cytology - A Cohort Study. Indian Journal of Endocrinology and Metabolism, 26(5), 446–452. https://doi.org/10.4103/ijem.ijem_75_22
Wang, Z., Lin, Y., Jiang, Y., Fu, R., Wang, Y., & Zhang, Q. (2022). The associations between thyroid-related hormones and the risk of thyroid cancer: An overall and dose-response meta-analysis. Frontiers in Endocrinology, 13. https://doi.org/10.3389/fendo.2022.992566
Xu, B., Gu, S.-Y., Zhou, N.-M., & Jiang, J.-J. (2023). Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis. Open Life Sciences, 18(1). https://doi.org/10.1515/biol-2022-0671
Zhang, S., Niu, S., & Zhou, L. (2025). Gender, FT4 levels, T stage, and BMI as predictors of TSH levels in thyroid cancer patients. Frontiers in Endocrinology, 16. https://doi.org/10.3389/fendo.2025.1422464
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Novitasari, Anak Agung Ayu Ngurah Susraini, Kadek Agus Suhardinata
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-ShareAlike 4.0 International License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
