Volume 28, Issue 2 (4-2025)                   J Arak Uni Med Sci 2025, 28(2): 141-146 | Back to browse issues page


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Talaei A, Rafiei F, Motamedi G, Chehrei A. The Effect of Metformin on Thyroid Nodules. J Arak Uni Med Sci 2025; 28 (2) :141-146
URL: http://jams.arakmu.ac.ir/article-1-7900-en.html
1- Professor of Endocrinology, Arak University of Medical Sciences, Arak, Iran , afsanehtalaeii@yahoo.com
2- Department Biostatistics, School of Medicine, Arak University of Medical Sciences, Arak, Iran
3- General Practitioner, Arak, Iran
4- Department of Pathology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
Abstract:   (823 Views)
Introduction: Thyroid nodules are highly prevalent. The role of insulin resistance in thyroid nodule formation has recently gained attention. While several studies have explored the relationship between metformin and insulin resistance, limited research has assessed the effect of metformin therapy on thyroid nodule volume and number. This study investigated the effect of metformin on the size and number of thyroid nodules.
Methods: A total of 240 euthyroid women with thyroid nodules were divided into four groups. Group 1 received levothyroxine 100 μg/day, Group 2 received metformin 500 mg twice daily, Group 3 received a combination of both drugs for three months, and Group 4 served as the control group with no treatment. Thyroid ultrasound was performed at baseline and after three months. Statistical analyses included the Kruskall–Wallis, Wilcoxon, and Chi-square tests, examined the differences of the size of thyroid nodules and the mean of thyroid hormones levels between groups, for Each group included 60 people and to compare the percentage of differences between the groups, respectively. Also P value less than 0.05 was considered meaningful.
Results: Results showed no statistically significant differences in thyroid hormone levels after treatment among the three groups except the levothyroxine group. Additionally, only the levothyroxine group showed a significant post-treatment decrease in TSH and increase in T4. Thyroid nodule size significantly decreased in the levothyroxine group and the levothyroxine-metformin combination group compared to the metformin-alone and control groups.
Conclusions: This study indicates that metformin does not reduce the size of thyroid nodules, contradicting studies suggesting its potential antineoplastic effects on the thyroid. However, the study duration may be insufficient for definitive conclusions, necessitating further high-quality studies with larger sample sizes and longer follow-up periods.
 
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Type of Study: Original Atricle | Subject: Internal
Received: 2024/12/5 | Accepted: 2025/01/6

References
1. Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS. The diagnosis and management of thyroid nodules: a review. JAMA. 2018;319(9):914-24. pmid: 29509871 doi: 10.1001/jama.2018.0898.
2. Wang H, Jiang Y, Song J, Liang H, Liu Y, Huang J, et al. The risk of perchlorate and iodine on the incidence of thyroid tumors and nodular goiter: a case-control study in southeastern China. Environ Health. 2022;21(1):4. pmid: 34980104 doi: 10.1186/s12940-021-00818-8
3. Tang Z, Zhang J, Zhou Q, Xu S, Cai Z, Jiang G. Thyroid Cancer "epidemic": a socio-environmental health problem needs collaborative efforts. Environ Sci Technol. 2020; 54(7):3725-7. pmid: 32191442 doi: 10.1021/acs.est.0c00852
4. Kushchayeva YS, Kushchayev SV, Startzell M, Cochran E, Auh S, Dai Y, et al. Thyroid abnormalities in patients with extreme insulin resistance syndromes. J Clin Endocrinol Metab. 2019;104(6):2216-28. pmid: 30657911 doi: 10.1210/jc.2018-02289
5. Zhao J, Zhang Q, Yang Y, Yao J, Liao L, et al. High prevalence of thyroid carcinoma in patients with insulin resistance: a meta-analysis of case-control studies. Aging (Albany NY). 2021;13(18):22232-41. pmid: 34550096 doi: 10.18632/aging.203529
6. Faggi L, Giustina A, Tulipano G. Effects of metformin on cell growth and AMPK activity in pituitary adenoma cell cultures, focusing on the interaction with adenylyl cyclase activating signals. Mol Cell Endocrinol. 2018;470:60-74. pmid: 28962892 doi: 10.1016/j.mce.2017.09.030
7. Riemann A, Blaschke M, Jauho-Ghadimi A, Siggelkow H, Gollisch KSC. Metformin improves the hepatic steatosis index in non-obese patients with polycystic ovary syndrome. J Clin Med. 2022;11(15):4294. pmid: 35893386 doi: 10.3390/jcm11154294.
8. Kurelac I, Umesh Ganesh N, Iorio M, Porcelli AM, Gasparre G. The multifaceted effects of metformin on tumor microenvironment. Semin Cell Dev Biol. 2020;98:90-7. pmid: 31091466 doi: 10.1016/j.semcdb.2019.05.010
9. Cannarella R, Condorelli RA, Barbagallo F, Aversa A, Calogero AE, La Vignera S. TSH lowering effects of metformin: a possible mechanism of action. J Endocrinol Invest. 2021;44(7):1547-50. pmid: 33058005 doi: 10.1007/s40618-020-01445-9.
10. He X, Wu D, Hu C, Xu T, Liu Y, Liu C, et al. Role of metformin in the treatment of patients with thyroid nodules and insulin resistance: a systematic review and meta-analysis. Thyroid. 2019;29(3):359-67. pmid: 30595105 doi: 10.1089/thy.2017.0707.
11. Smith TJ. Insulin-like growth factor pathway and the thyroid. Front Endocrinol (Lausanne). 2021;12:653627. pmid: 34149612 doi: 10.3389/fendo.2021.653627.
12. Tsui S, Naik V, Hoa N, Hwang CJ, Afifiyan NF, Sinha Hikim A, et al. Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves' disease. J Immunol. 2008; 181(6):4397-405. pmid: 18768899 doi: 10.4049/jimmunol.181.6.4397
13. Kanigur Sultuybek G, Soydas T, Yenmis G. NF-κB as the mediator of metformin's effect on ageing and ageing-related diseases. Clin Exp Pharmacol Physiol. 2019;46(5):413-22. pmid: 30754072 doi: 10.1111/1440-1681.13073
14. Rotondi M, Coperchini F, Pignatti P, Magri F, Chiovato L. Metformin reverts the secretion of CXCL8 induced by TNF-α in primary cultures of human thyroid cells: an additional indirect anti-tumor effect of the drug. J Clin Endocrinol Metab. 2015;100(3):E427-32. pmid: 25590211 doi: 10.1210/jc.2014-3045
15. Bayliss JA, Lemus MB, Santos VV, Deo M, Davies JS, Kemp BE, et al. Metformin Prevents Nigrostriatal Dopamine Degeneration Independent of AMPK Activation in Dopamine Neurons. PLoS One. 2016;11(7):e0159381. pmid: 27467571 doi: 10.1371/journal.pone.0159381
16. Joffe BI, Distiller LA. Diabetes mellitus and hypothyroidism: Strange bedfellows or mutual companions? World J Diabetes. 2014;5(6):901-4. pmid: 25512794 doi: 10.4239/wjd.v5.i6.901
17. Tseng CH. Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus. Eur J Cancer. 2014;50(16):2831-7. pmid: 25201464 doi: 10.1016/j.ejca.2014.08.007
18. Chen G, Nicula D, Renko K, Derwahl M. Synergistic anti-proliferative effect of metformin and sorafenib on growth of anaplastic thyroid cancer cells and their stem cells. Oncol Rep. 2015;33(4):1994-2000. pmid: 25683253 doi: 10.3892/or.2015.3805
19. Han G, Gong H, Wang Y, Guo S, Liu K. AMPK/mTOR-mediated inhibition of survivin partly contributes to metformin-induced apoptosis in human gastric cancer cell. Cancer Biol Ther. 2015;16(1):77-87. pmid: 25456211 doi: 10.4161/15384047.2014.987021.
20. Karimifar M, Aminorroaya A, Amini M, Mirfendereski T, Iraj B, Feizi A, et al. Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: A randomized placebo-controlled clinical trial. J Res Med Sci. 2014;19(11):1019-26. pmid: 25657744
21. Rezzónico J, Rezzónico M, Pusiol E, Pitoia F, Niepomniszcze H. Metformin treatment for small benign thyroid nodules in patients with insulin resistance. Metab Syndr Relat Disord. 2011;9(1):69-75. pmid: 21128816 doi: 10.1089/met.2010.0026
22. Cappelli C, Rotondi M, Pirola I, Agosti B, Formenti A, Zarra E, et al. Thyreotropin levels in diabetic patients on metformin treatment. Eur J Endocrinol. 2012;167(2):261-5. pmid: 22645202 doi: 10.1530/EJE-12-0225
23. Lupoli R, Di Minno A, Tortora A, Ambrosino P, Lupoli GA, Di Minno MN. Effects of treatment with metformin on TSH levels: a meta-analysis of literature studies. J Clin Endocrinol Metab. 2014;99(1):E143-148. pmid: 24203069 doi: 10.1210/jc.2013-2965
24. Rotondi M, Cappelli C, Magri F, Botta R, Dionisio R, Iacobello C, et al. Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2011;75(3):378-81. pmid: 21521311 doi: 10.1111/j.1365-2265.2011.04042.x.
25. Anil C, Kut A, Atesagaoglu B, Nar A, Bascil Tutuncu N, Gursoy A. Metformin decreases thyroid volume and nodule size in subjects with insulin resistance: a preliminary study. Med Princ Pract. 2016;25(3):233-6. pmid: 26618447 doi: 10.1159/000442821.
26. Sui M, Yu Y, Zhang H, Di H, Liu C, Fan Y. Efficacy of metformin for benign thyroid nodules in subjects with insulin resistance: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2018;9:494. pmid: 30233494 doi: 10.3389/fendo.2018.00494
27. Vigersky RA, Filmore-Nassar A, Glass AR. Thyrotropin suppression by metformin. J Clin Endocrinol Metab. 2006;91(1):225-7. pmid: 16219720 doi: 10.1210/jc.2005-1210.
28. Dos Santos PB, Gertrudes LN, Conceição FL, de Andrade BM, de Carvalho DP, Vaisman M, et al. Effects of metformin on TSH levels and benign nodular goiter volume in patients without insulin resistance or iodine insufficiency. Front Endocrinol (Lausanne). 2019;10:465. pmid: 31379740 doi: 10.3389/fendo.2019.00465
29. Olgun ME, Pire G, Güney İB. Effects of metformin therapy on thyroid volume and functions in patients with newly diagnosed type 2 diabetes mellitus: a single-center prospective study. Endocr Metab Immune Disord Drug Targets. 2024;24(15):1842-55. pmid: 38676519 doi: 10.2174/0118715303307313240315162000
30. Krysiak R, Szkrobka W, Okopien B. The effect of metformin on hypothalamic-pituitary-thyroid axis activity in women with interferon-induced hypothyroidism: a pilot study. Exp Clin Endocrinol Diabetes. 2016;124(2):71-6. pmid: 26895275 doi: 10.1055/s-0035-1565207
31. Becker C, Jick SS, Meier CR, Bodmer M. No evidence for a decreased risk of thyroid cancer in association with use of metformin or other antidiabetic drugs: a case-control study. BMC Cancer. 2015;15:719. pmid: 26475035 10.1186/s12885-015-1719-6. doi:
32. Layegh P, Asadi A, Jangjoo A, Layegh P, Nematy M, Salehi M, et al. "Comparison of thyroid volume, TSH, free t4 and the prevalence of thyroid nodules in obese and non-obese subjects and correlation of these parameters with insulin resistance status". Caspian J Intern Med. 2020;11(3):278-82. pmid: 32874434 doi: 10.22088/cjim.11.3.278.

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