OBESITY AS A MODIFIABLE DETERMINANT OF THYROID DYSFUNCTION, STRUCTURAL CHANGES, AND THYROID CANCER
Abstract
Introduction: Obesity has become a global health problem with rapidly increasing prevalence across all age groups. Accumulating evidence suggests that excess adiposity affects thyroid function and morphology and may contribute to the rising incidence of thyroid cancer. This review summarizes current knowledge on the interplay between obesity, thyroid physiology, thyroid structural alterations, and thyroid cancer risk.
Methods: A comprehensive literature search was conducted using PubMed and Google Scholar, focusing on systematic reviews and meta-analyses. Keywords such as “obesity”, “body mass index”, “thyroid nodules”, “thyroid cancer”, “bariatric surgery”, and “GLP-1 RA” guided the search. Selected studies were qualitatively analyzed.
Results: Obesity was strongly associated with elevated TSH, thyroid hypertrophy, increased thyroid volume, and higher prevalence of nodules, often with more suspicious cytology. Meta-analyses showed that each 5-unit increase in BMI corresponds to an increase up to a 30% in thyroid cancer risk, particularly for papillary, follicular, and anaplastic subtypes. Mechanisms include hyperleptinemia, chronic inflammation, insulin resistance, altered estrogen signaling, and oxidative stress. Weight-loss interventions, including bariatric surgery and GLP-1 receptor agonists, were associated with the improvements of thyroid function and morphology.
Conclusions: Obesity is a significant and modifiable determinant of thyroid dysfunction and thyroid cancer. Effective weight management may reverse obesity-related thyroid alterations and should be integrated into clinical care and preventive strategies.
References
Tung, J. Y. L., Poon, G. W. K., Du, J., & Wong, K. K. Y. (2023). Obesity in children and adolescents: Overview of the diagnosis and management. In Chronic Diseases and Translational Medicine (Vol. 9, Issue 2). https://doi.org/10.1002/cdt3.58
Blüher, M. (2019). Obesity: global epidemiology and pathogenesis. In Nature Reviews Endocrinology (Vol. 15, Issue 5). https://doi.org/10.1038/s41574-019-0176-8
Sarma, S., Sockalingam, S., & Dash, S. (2021). Obesity as a multisystem disease: Trends in obesity rates and obesity-related complications. In Diabetes, Obesity and Metabolism (Vol. 23, Issue S1). https://doi.org/10.1111/dom.14290
Lin, X., & Li, H. (2021). Obesity: Epidemiology, Pathophysiology, and Therapeutics. In Frontiers in Endocrinology (Vol. 12). https://doi.org/10.3389/fendo.2021.706978
Mahmoud, A. M. (2022). An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions. In International Journal of Molecular Sciences (Vol. 23, Issue 3). https://doi.org/10.3390/ijms23031341
Pati, S., Irfan, W., Jameel, A., Ahmed, S., & Shahid, R. K. (2023). Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management. In Cancers (Vol. 15, Issue 2). https://doi.org/10.3390/cancers15020485
WHO. (2000). (1999: Geneva, Switzerland) & World Health Organization. (2000). Obesity : preventing and managing the global epidemic : report of a WHO consultation. World Health Organization (Vol. 894).
Salminen, P., Kow, L., Aminian, A., Kaplan, L. M., Nimeri, A., Prager, G., Behrens, E., White, K. P., Shikora, S., & IFSO Experts Panel (2024). IFSO Consensus on Definitions and Clinical Practice Guidelines for Obesity Management-an International Delphi Study. Obesity surgery, 34(1), 30–42. https://doi.org/10.1007/s11695-023-06913-8
WHO. (2023). WHO acceleration plan to stop obesity. World Health Organization.
WHO. (2023) Health service delivery framework for prevention and management of obesity. World Health Organization.
Fitch, A. K., & Bays, H. E. (2022). Obesity definition, diagnosis, bias, standard operating procedures (SOPs), and telehealth: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022. Obesity Pillars, 1. https://doi.org/10.1016/j.obpill.2021.100004
WHO (2025, May 7). Obesity and overweight. Retrieved from https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
Santini, F., Marzullo, P., Rotondi, M., Ceccarini, G., Pagano, L., Ippolito, S., Chiovato, L., & Biondi, B. (2014). Mechanisms in endocrinology: the crosstalk between thyroid gland and adipose tissue: signal integration in health and disease. European journal of endocrinology, 171(4), R137-R152.
Biondi, B. (2024). Subclinical Hypothyroidism in Patients with Obesity and Metabolic Syndrome: A Narrative Review. In Nutrients (Vol. 16, Issue 1). https://doi.org/10.3390/nu16010087
Bjergved, L., Jørgensen, T., Perrild, H., Laurberg, P., Krejbjerg, A., Ovesen, L., Rasmussen, L. B., & Knudsen, N. (2014). Thyroid function and body weight: A community-based longitudinal study. PLoS ONE, 9(4). https://doi.org/10.1371/journal.pone.0093515
Guan, B., Chen, Y. Y., Yang, J., Yang, W., & Wang, C. (2017). Effect of Bariatric Surgery on Thyroid Function in Obese Patients: a Systematic Review and Meta-Analysis. In Obesity Surgery (Vol. 27, Issue 12). https://doi.org/10.1007/s11695-017-2965-2
Baranowska-Bik, A., & Bik, W. (2020). The Association of Obesity with Autoimmune Thyroiditis and Thyroid Function-Possible Mechanisms of Bilateral Interaction. In International Journal of Endocrinology (Vol. 2020). https://doi.org/10.1155/2020/8894792
Szczepanek-Parulska, E., Zybek-Kocik, A., Woliński, K., Czarnocka, B., & Ruchała, M. (2016). Does TSH Trigger the Anti-thyroid Autoimmune Processes? Observation on a Large Cohort of Naive Patients with Thyroid Hemiagenesis. Archivum Immunologiae et Therapiae Experimentalis, 64(4). https://doi.org/10.1007/s00005-016-0393-y
Wu, Z., Xi, Z., Xiao, Y., Zhao, X., Li, J., Feng, N., Hu, L., Zheng, R., Zhang, N., Wang, S., & Huang, T. (2022). TSH-TSHR axis promotes tumor immune evasion. Journal for ImmunoTherapy of Cancer, 10(1). https://doi.org/10.1136/jitc-2021-004049
Mastrototaro, L., & Roden, M. (2021). Insulin resistance and insulin sensitizing agents. In Metabolism: Clinical and Experimental (Vol. 125). https://doi.org/10.1016/j.metabol.2021.154892
Chen, G., Xu, S., Renko, K., & Derwahl, M. (2012). Metformin inhibits growth of thyroid carcinoma cells, suppresses self-renewal of derived cancer stem cells, and potentiates the effect of chemotherapeutic agents. Journal of Clinical Endocrinology and Metabolism, 97(4). https://doi.org/10.1210/jc.2011-1754
Lomtadze, N., Giorgadze, E., Janjgava, S., Kacharava, T., & Taboridze, I. (2023). The Relationship between Insulin Resistance and Thyroid Volume in Georgia. Endocrine, Metabolic & Immune Disorders - Drug Targets, 23(10). https://doi.org/10.2174/1871530323666230220093432
Marzullo, P., Minocci, A., Tagliaferri, M. A., Guzzaloni, G., di Blasio, A., de Medici, C., Aimaretti, G., & Liuzzi, A. (2010). Investigations of thyroid hormones and antibodies in obesity: Leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants. Journal of Clinical Endocrinology and Metabolism, 95(8). https://doi.org/10.1210/jc.2009-2798
Song, R. H., Wang, B., Yao, Q. M., Li, Q., Jia, X., & Zhang, J. A. (2019). The Impact of Obesity on Thyroid Autoimmunity and Dysfunction: A Systematic Review and Meta-Analysis. In Frontiers in Immunology (Vol. 10). https://doi.org/10.3389/fimmu.2019.02349
Pemayun, T. G. D. (2016). Current Diagnosis and Management of Thyroid Nodules. In Acta medica Indonesiana (Vol. 48, Issue 3).
Demetriou, E., Economides, A., Fokou, M., Lamnisos, D., Paschou, S. A., Papageorgis, P., & Economides, P. A. (2025). Adiposity is associated with a higher number of thyroid nodules and worse fine-needle aspiration outcomes. European Thyroid Journal, 14(1), e240176. Retrieved Dec 7, 2025, from https://doi.org/10.1530/ETJ-24-0176
Poller, D. N., Cochand-Priollet, B., & Trimboli, P. (2021). Thyroid FNA terminology: The case for a single unified international system for thyroid FNA reporting. In Cytopathology (Vol. 32, Issue 6). https://doi.org/10.1111/cyt.13017
Fokou, M., Economides, A., Demetriou, E., Lamnisos, D., Agouridis, A. P., Papageorgis, P., & Economides, P. A. (2025). Adiposity Is Associated with a Higher Risk of Thyroid Malignancy in Patients with Hashimoto’s Thyroiditis. Diagnostics, 15(7), 853. https://doi.org/10.3390/diagnostics15070853
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6). https://doi.org/10.3322/caac.21492
Wirth, S., Syleouni, M. E., Karavasiloglou, N., Rinaldi, S., Korol, D., Wanner, M., & Rohrmann, S. (2021). Incidence and mortality trends of thyroid cancer from 1980 to 2016. Swiss Medical Weekly, 151(43–44). https://doi.org/10.4414/smw.2021.w30029
Enewold, L., Zhu, K., Ron, E., Marrogi, A. J., Stojadinovic, A., Peoples, G. E., & Devesa, S. S. (2009). Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005. Cancer Epidemiology Biomarkers and Prevention, 18(3). https://doi.org/10.1158/1055-9965.EPI-08-0960
Zhang, J., & Xu, S. (2024). High aggressiveness of papillary thyroid cancer: from clinical evidence to regulatory cellular networks. In Cell Death Discovery (Vol. 10, Issue 1). https://doi.org/10.1038/s41420-024-02157-2
Shen, J., Yan, M., Chen, L., Ou, D., Yao, J., Feng, N., Zhou, X., Lei, Z., & Xu, D. (2024). Prognosis and influencing factors of follicular thyroid cancer. Cancer Medicine, 13(1). https://doi.org/10.1002/cam4.6727
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. In International Journal of Molecular Sciences (Vol. 26, Issue 11). https://doi.org/10.3390/ijms26115173
Li, Y., Zhang, J., Zhou, H., & Du, Z. (2022). Anticancer effects of natural phytochemicals in anaplastic thyroid cancer (Review). In Oncology Reports (Vol. 48, Issue 3). https://doi.org/10.3892/or.2022.8368
Yin, D. tao, He, H., Yu, K., Xie, J., Lei, M., Ma, R., Li, H., Wang, Y., & Liu, Z. (2018). The association between thyroid cancer and insulin resistance, metabolic syndrome and its components: A systematic review and meta-analysis. In International Journal of Surgery (Vol. 57). https://doi.org/10.1016/j.ijsu.2018.07.013
Franchini, F., Palatucci, G., Colao, A., Ungaro, P., Macchia, P. E., & Nettore, I. C. (2022). Obesity and Thyroid Cancer Risk: An Update. In International Journal of Environmental Research and Public Health (Vol. 19, Issue 3). https://doi.org/10.3390/ijerph19031116
Mirkatouli, N. B., Hirota, S., & Yoshinaga, S. (2023). Thyroid cancer risk after radiation exposure in adults - systematic review and meta-analysis. In Journal of Radiation Research (Vol. 64, Issue 6). https://doi.org/10.1093/jrr/rrad073
Derwahl, M., & Nicula, D. (2014). Estrogen and its role in thyroid cancer. Endocrine-Related Cancer, 21(5). https://doi.org/10.1530/ERC-14-0053
Lee, J. H., Chai, Y. J., & Yi, K. H. (2021). Effect of Cigarette Smoking on Thyroid Cancer: Meta-Analysis. Endocrinology and Metabolism, 36(3). https://doi.org/10.3803/ENM.2021.954
Dong, W. W., Zhang, D. L., Wang, Z. H., Lv, C. Z., Zhang, P., & Zhang, H. (2022). Different types of diabetes mellitus and risk of thyroid cancer: A meta-analysis of cohort studies. In Frontiers in Endocrinology (Vol. 13). https://doi.org/10.3389/fendo.2022.971213
Ma, J., Huang, M., Wang, L., Ye, W., Tong, Y., & Wang, H. (2015). Obesity and risk of thyroid cancer: Evidence from a Meta-Analysis of 21 observational studies. Medical Science Monitor, 21. https://doi.org/10.12659/MSM.892035
Zhao, Z. G., Guo, X. G., Ba, C. X., Wang, W., Yang, Y. Y., Wang, J., & Cao, H. Y. (2012). Overweight, obesity and thyroid cancer risk: A meta-analysis of cohort studies. Journal of International Medical Research, 40(6). https://doi.org/10.1177/030006051204000601
Rezzónico, J. N., Rezzónico, M., Pusiol, E., Pitoia, F., & Niepomniszcze, H. (2009). Increased prevalence of insulin resistance in patients with differentiated thyroid carcinoma. Metabolic Syndrome and Related Disorders, 7(4). https://doi.org/10.1089/met.2008.0062
Nettore, I. C., Rocca, C., Mancino, G., Albano, L., Amelio, D., Grande, F., Puoci, F., Pasqua, T., Desiderio, S., Mazza, R., Terracciano, D., Colao, A., Bèguinot, F., Russo, G. L., Dentice, M., Macchia, P. E., Sinicropi, M. S., Angelone, T., & Ungaro, P. (2019). Quercetin and its derivative Q2 modulate chromatin dynamics in adipogenesis and Q2 prevents obesity and metabolic disorders in rats. Journal of Nutritional Biochemistry, 69. https://doi.org/10.1016/j.jnutbio.2019.03.019
Kawai, T., Autieri, M. v., & Scalia, R. (2021). Adipose tissue inflammation and metabolic dysfunction in obesity. American Journal of Physiology - Cell Physiology, 320(3). https://doi.org/10.1152/ajpcell.00379.2020
Haase, J., Weyer, U., Immig, K., Klöting, N., Blüher, M., Eilers, J., Bechmann, I., & Gericke, M. (2014). Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Diabetologia, 57(3). https://doi.org/10.1007/s00125-013-3139-y
Zheng, R., Chen, G., Li, X., Wei, X., Liu, C., & Derwahl, M. (2019). Effect of IL-6 on proliferation of human thyroid anaplastic cancer stem cells. International Journal of Clinical and Experimental Pathology, 12(11).
Zhao, J., Wen, J., Wang, S., Yao, J., Liao, L., & Dong, J. (2020). Association between adipokines and thyroid carcinoma: A meta-analysis of case-control studies. BMC Cancer, 20(1). https://doi.org/10.1186/s12885-020-07299-x
Celano, M., Maggisano, V., Lepore, S. M., Sponziello, M., Pecce, V., Verrienti, A., Durante, C., Maranghi, M., Lucia, P., Bulotta, S., Damante, G., & Russo, D. (2019). Expression of Leptin Receptor and Effects of Leptin on Papillary Thyroid Carcinoma Cells. International Journal of Endocrinology, 2019. https://doi.org/10.1155/2019/5031696
Nigro, E., Orlandella, F. M., Polito, R., Mariniello, R. M., Monaco, M. L., Mallardo, M., de Stefano, A. E., Iervolino, P. L. C., Salvatore, G., & Daniele, A. (2021). Adiponectin and leptin exert antagonizing effects on proliferation and motility of papillary thyroid cancer cell lines. Journal of Physiology and Biochemistry, 77(2). https://doi.org/10.1007/s13105-021-00789-x
Artim, S. C., Mendrola, J. M., & Lemmon, M. A. (2012). Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family. Biochemical Journal, 448(2). https://doi.org/10.1042/BJ20121365
Vella, V., Sciacca, L., Pandini, G., Mineo, R., Squatrito, S., Vigneri, R., & Belfiore, A. (2001). The IGF system in thyroid cancer: New concepts. In Journal of Clinical Pathology - Molecular Pathology (Vol. 54, Issue 3). https://doi.org/10.1136/mp.54.3.121
Bowers, L. W., Rossi, E. L., O’Flanagan, C. H., de Graffenried, L. A., & Hursting, S. D. (2015). The role of the insulin/IGF system in cancer: Lessons learned from clinical trials and the energy balance-cancer link. In Frontiers in Endocrinology (Vol. 6, Issue MAY). https://doi.org/10.3389/fendo.2015.00077
Vella, V., & Malaguarnera, R. (2018). The emerging role of insulin receptor isoforms in thyroid cancer: Clinical implications and new perspectives. In International Journal of Molecular Sciences (Vol. 19, Issue 12). https://doi.org/10.3390/ijms19123814
Pazaitou-Panayiotou, K., Polyzos, S. A., & Mantzoros, C. S. (2013). Obesity and thyroid cancer: Epidemiologic associations and underlying mechanisms. In Obesity Reviews (Vol. 14, Issue 12). https://doi.org/10.1111/obr.12070
Liu, J., Xu, T., Ma, L., & Chang, W. (2021). Signal Pathway of Estrogen and Estrogen Receptor in the Development of Thyroid Cancer. In Frontiers in Oncology (Vol. 11). https://doi.org/10.3389/fonc.2021.593479
Xing, M. (2012). Oxidative stress: A new risk factor for thyroid cancer. In Endocrine-Related Cancer (Vol. 19, Issue 1). https://doi.org/10.1530/ERC-11-0360
Karbownik-Lewińska, M., & Kokoszko-Bilska, A. (2012). Oxidative damage to macromolecules in the thyroid - Experimental evidence. In Thyroid Research (Vol. 5, Issue 1). https://doi.org/10.1186/1756-6614-5-25
Costa, A., Scholer-Dahirel, A., & Mechta-Grigoriou, F. (2014). The role of reactive oxygen species and metabolism on cancer cells and their microenvironment. In Seminars in Cancer Biology (Vol. 25). https://doi.org/10.1016/j.semcancer.2013.12.007
Neale, E. P., Batterham, M. J., & Tapsell, L. C. (2016). Consumption of a healthy dietary pattern results in significant reductions in C-reactive protein levels in adults: A meta-analysis. In Nutrition Research (Vol. 36, Issue 5). https://doi.org/10.1016/j.nutres.2016.02.009
Marx, W., Veronese, N., Kelly, J. T., Smith, L., Hockey, M., Collins, S., Trakman, G. L., Hoare, E., Teasdale, S. B., Wade, A., Lane, M., Aslam, H., Davis, J. A., O’neil, A., Shivappa, N., Hebert, J. R., Blekkenhorst, L. C., Berk, M., Segasby, T., & Jacka, F. (2021). The Dietary Inflammatory Index and Human Health: An Umbrella Review of Meta-Analyses of Observational Studies. In Advances in Nutrition (Vol. 12, Issue 5). https://doi.org/10.1093/advances/nmab037
Hisan, U. K., Myung, S. K., & Nguyen, G. V. (2025). Associations Between Obesity and Risk of Thyroid Cancer: A Meta-Analysis of Cohort Studies. Nutrition and Cancer, 77(2). https://doi.org/10.1080/01635581.2024.2419488
Schmid, D., Ricci, C., Behrens, G., & Leitzmann, M. F. (2015). Adiposity and risk of thyroid cancer: A systematic review and meta-analysis. In Obesity Reviews (Vol. 16, Issue 12). https://doi.org/10.1111/obr.12321
Sadeghi, H., Rafei, M., Bahrami, M., Haghdoost, A., & Shabani, Y. (2018). Attributable risk fraction of four lifestyle risk factors of thyroid cancer: A meta-analysis. Journal of Public Health (United Kingdom), 40(2). https://doi.org/10.1093/pubmed/fdx088
de Sousa, P. A. M., Pereira, J. R. D., Carneiro, J. R. I., de Vasconcelos, A. L., Fortunato, R. S., Carvalho, D. P., & Teixeira, P. de F. dos S. (2023). Impact of Bariatric Surgery on Thyroid Morphology and Thyroid Function. Obesity Surgery, 33(10). https://doi.org/10.1007/s11695-023-06779-w
Soyer, A. K., Ertuna, G. N., Çolakoğlu, M. K., Başer, H., Aydın, C., Topaloğlu, O., Ersoy, R., & Çakır, B. (2025). Thyroid Volume Stabilization and Nodule Progression After Bariatric Surgery: Insights from a Retrospective Study. Obesity Surgery, 35(10). https://doi.org/10.1007/s11695-025-08229-1
Bezin, J., Gouverneur, A., Penichon, M., Mathieu, C., Garrel, R., Hillaire-Buys, D., Pariente, A., & Faillie, J. L. (2023). GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care, 46(2). https://doi.org/10.2337/dc22-1148
Baxter, S. M., Lund, L. C., Andersen, J. H., Brix, T. H., Hegedüs, L., Hsieh, M. H. C., Su, C. T. T., Cheng, M. C. Y., Chang, Z. C. J., Lai, E. C. C., Hussain, S., Chu, C., Gomes, T., Antoniou, T., Eskander, A., Bouck, Z., Tadrous, M., Bea, S., Choi, E. Y., Shin, J., Y., Modig, K., Talbäck, M., Ljung, R., Gulseth, H. L., Karlstad, Ø., Hicks, B., Pottegård, A. (2025). Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study. Thyroid, 35(1). https://doi.org/10.1089/thy.2024.0387
Nagendra, L., BG, H., Sharma, M., & Dutta, D. (2023). Semaglutide and cancer: A systematic review and meta-analysis: Semaglutide and cancer. Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 17(9). https://doi.org/10.1016/j.dsx.2023.102834
Levy, S., Attia, A., Elshazli, R. M., Abdelmaksoud, A., Tatum, D., Aiash, H., & Toraih, E. A. (2025). Differential Effects of GLP-1 Receptor Agonists on Cancer Risk in Obesity: A Nationwide Analysis of 1.1 Million Patients. Cancers, 17(1). https://doi.org/10.3390/cancers17010078
Views:
34
Downloads:
6
Copyright (c) 2025 Klaudia Baran, Aleksandra Grygorowicz, Michał Ględa, Michał Szyszka, Weronika Radecka, Weronika Kozak, Agnieszka Szreiber, Karol Grela, Karolina Nowacka, Kamil Jabłoński, Anna Woźniak

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.

