OBJECTIVE: patients with type 2 diabetes (T2DM) and obesity are generally known to have increased risk of various types of cancer, though studies addressing associations between T2DM/obesity and thyroid cancer are inconclusive. The aim of our study was to evaluate the risk of thyroid cancer focusing on diabetic patients under conditions of euthyroid status. A retrospective study in 184 patients was performed. Three cohorts were established according to tumor histology: malignant (M), benign (B) and low-risk carcinoma (MB). Fisher's exact test and Kruskal-Wallis one-way ANOVA of ranks were used for statistical analysis. The M (39.1 %), B (57.6 %) and MB (3.3 %) cohorts had comparable age (p=0.4), BMI (p=0.452), glycaemia (p=0.834), Hb1AC (p=0.157) and HOMA-IR (p=0.235). T2DM patients had larger thyroid gland volumes (28.8 vs 17.6 mL;p=0.001) compared to the cohort with normal glucose tolerance. Compared to women, men had more frequently present distal metastases (p=0.017), minimally invasive disease (p=0.027), more advanced staging (p=0.01) and positive pathogenic mutations in the TERT gene (p=0.009);these results were also significant for the diabetic male cohort (p=0.026). Type 2 diabetes and obesity are not risk factors for thyroid cancer, but a subgroup of males seems to have thyroid cancers of poorer prognosis. In general, diabetic patients with insulin resistance and hyperinsulinemia are also prone to have a goiter. KEY WORDS: Thyroid cancer, Type 2 diabetes, Obesity, Thyroid nodule, Insulin resistance.

Institute of Endocrinology Prague Czech Republic

Zobrazit více v PubMed

Megwalu UC, Moon PK. Thyroid Cancer Incidence and Mortality Trends in the United States: 2000–2018. Thyroid. 2022;32:560–570. doi: 10.1089/thy.2021.0662. PubMed DOI

Ito Y, Nikiforov YE, Schlumberger M, Vigneri R. Increasing incidence of thyroid cancer:controversies explored. Nat Rev Endocrinol. 2013;9:178–184. doi: 10.1038/nrendo.2012.257. PubMed DOI

Roti E, Degli Uberti EC, Bondanelli, Braverman LE. Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. Eur J Endocrinol. 2008;159:659–73. doi: 10.1530/EJE-07-0896. PubMed DOI

Zhang W, Bai X, Ge H, Cui H, Wei Z, Han G. Meta-analysis in the association between obesity and risk of thyroid cancer. Int J Clin Exp Med. 2014;15:5268–74. PubMed PMC

Standl E, Khunti K, Hansen TB, Schnell O. The global epidemics of diabetes in the 21st century: Current situation and perspectives. Eur J Prev Cardiol. 2019;26:7–14. doi: 10.1177/2047487319881021. PubMed DOI

Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017;3:2239–2251. doi: 10.1016/S0140-6736(17)30058-2. PubMed DOI

Bellary S, Kyrou I, Brown JE, Bailey CJ. Type 2 diabetes mellitus in older adults: clinical considerations and management. Nat Rev Endocrinol. 2021;17:534–548. doi: 10.1038/s41574-021-00512-2. PubMed DOI

La Vecchia C, Negri E, Franceschi S, D’Avanzo B, Boyle P. A case-control study of diabetes mellitus and cancer risk. Br J Cancer. 1994;70:950–3. doi: 10.1038/bjc.1994.427. PubMed DOI PMC

Paes JE, Hua K, Nagy R, Kloos RT, Jarjoura D, Ringel MD. The relationship between body mass index and thyroid cancer pathology features and outcomes: a clinicopathological cohort study. J Clin Endocrinol Metab. 2010;95:4244–5p. doi: 10.1210/jc.2010-0440. PubMed DOI PMC

Biondi B, Kahaly GJ, Robertson RP. Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders. Endocr Rev. 2019;1:789–824. doi: 10.1210/er.2018-00163. PubMed DOI PMC

Biondi B, Cappola AR, Cooper DS. Subclinical Hypothyroidism: A Review. JAMA. 2019;322:153–160. doi: 10.1001/jama.2019.9052. PubMed DOI

Waring AC, Arnold AM, Newman AB, Bùzková P, Hirsch C, Cappola AR. Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin Endocrinol Metab. 2012;97:3944–50. doi: 10.1210/jc.2012-2481. PubMed DOI PMC

ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Cusi K, et al. American Diabetes Association. Addendum. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46:S49–S67. doi: 10.2337/dc23-S004. PubMed DOI PMC

Pearce SH, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, Wemeau JL. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J. 2013;2:215–28. doi: 10.1159/000356507. PubMed DOI PMC

Ladenson PW, Singer PA, Ain KB, Bagchi N, Bigos ST, Levy EG, Smith SASA, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern. 2000;160:1573–1575. doi: 10.1001/archinte.160.11.1573. PubMed DOI

American Diabetes Association. Standards of medical care in diabetes-2018: Diabetes Care. 2018;31:S12–S54. doi: 10.2337/dc08-S012. PubMed DOI

Dieringer P, Klass EM, Caine B, Smith-Gagen J. Associations between body mass and papillary thyroid cancer stage and tumor size: a population-based study. J Cancer Res Clin. 2015;141:93–8. doi: 10.1007/s00432-014-1792-2. PubMed DOI PMC

Roh E, Noh E, Hwang SY, Kim JA, Song E, Choi KM, Baik SH, et al. Increased Risk of Type 2 Diabetes in Patients With Thyroid Cancer After Thyroidectomy: A Nationwide Cohort Study. J Clin Endocrinol Met. 2022;17:e1047–e1056. doi: 10.1210/clinem/dgab776. PubMed DOI

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58:429–42. doi: 10.1007/s00125-014-3460-0. PubMed DOI

Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27:1487–95. doi: 10.2337/diacare.27.6.1487. PubMed DOI

Grimmichova T, Pacesova P, Hill M, Pekova B, Vankova M, Moravcova J, Vrbikova J, et al. Thyroid Cancer Detection in a Routine Clinical Setting: Performance of ACR TI-RADS, FNAC, and Molecular Testing in Prospective Cohort Study. Biomedicines. 2022;10:954. doi: 10.3390/biomedicines10050954. PubMed DOI PMC

Miranda-Filho A, Lortet-Tieulent J, Bray F, Cao B, Franceschi S, Vaccarella S. Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet Diabetes Endocrinol. 2021;9:225–234. doi: 10.1016/S2213-8587(21)00027-9. PubMed DOI

Robenshtok E, Neeman B, Reches L, Ritter A, Bachar G, Kaminer K, Shimon I, et al. Adverse Histological Features of Differentiated Thyroid Cancer Are Commonly Found in Autopsy Studies: Implications for Treatment Guidelines. Thyroid. 2022;32:37–45. doi: 10.1089/thy.2021.0268. PubMed DOI

Pearson-Stuttard J, Papadimitriou N, Markozannes G, Cividini S, Kakourou A, Gill D, Rizos EC, et al. Type 2 Diabetes and Cancer: An Umbrella Review of Observational and Mendelian Randomization Studies. Cancer Epidemiol. 2021;30:1218–1228. doi: 10.1158/1055-9965.EPI-20-1245. PubMed DOI PMC

Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern. 2006;25:1871–7. doi: 10.1001/archinte.166.17.1871. PubMed DOI

Grega T, Vojtechova G, Gregova M, Zavoral M, Suchanek S. Pathophysiological Characteristics Linking Type 2 Diabetes Mellitus and Colorectal Neoplasia. Physiol Res. 2021;31:509–522. doi: 10.33549/physiolres.934631. PubMed DOI PMC

Saarela K, Tuomilehto J, Sund R, Keskimaki I, Hartikainen R, Pukkala E. Cancer incidence among Finnish people with type 2 diabetes during 1989–2014. Eur J Epidemiol. 2019;34:259–265. doi: 10.1007/s10654-018-0438-0. PubMed DOI

Goto A, Yamaji T, Sawada N, Momozawa Y, Kamatani Y, Kubo M, Shimazu T, et al. Diabetes and cancer risk: A Mendelian randomization study. Int J Cancer. 2020;146:712–719. doi: 10.1002/ijc.32310. PubMed DOI PMC

Aschebrook-Kilfoy B, Sabra MM, Brenner A, Moore SC, Ron E, Schatzkin A, Hollenbeck A, et al. Diabetes and thyroid cancer risk in the National Institutes of Health-AARP Diet and Health Study. Thyroid. 2011;21:957–63. doi: 10.1089/thy.2010.0396. PubMed DOI PMC

Fu M, Yang L, Wang H, Chen Y, Chen X, Hu Q, Sun H. Research progress into adipose tissue macrophages and insulin resistance. Physiol Res. 2023;72:287–299. doi: 10.33549/physiolres.935046. PubMed DOI PMC

Rapp K, Schroeder J, Klenk J, Ulmer H, Concin H, Diem G, Oberaigner W, et al. Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia. 2006;49:945–52. doi: 10.1007/s00125-006-0207-6. PubMed DOI

Yeo Y, Ma SH, Hwang Y, Horn-Ross PL, Hsing A, Lee KE. Diabetes mellitus and risk of thyroid cancer: a meta-analysis. PLoS One. 2014;13:e98135. doi: 10.1371/journal.pone.0098135. PubMed DOI PMC

Kitahara CM, Platz EA, Beane Freeman LE, Black A, Hsing AW, Linet MS, Park Y, et al. Physical activity, diabetes, and thyroid cancer risk: a pooled analysis of five prospective studies. Cancer Causes Control. 2012;23:463–471. https://doi.org/10.1007/s10552-012-9896-y, https://doi.org/10.1007/s10552-012-0039-2. PubMed DOI PMC

Luo J, Phillips L, Liu S, Wactawski-Wende J, Margolis KL. Diabetes Treatment, and Risk of Thyroid Cancer. J Clin Endocrinol Met. 2016;101:1243–8. https://doi.org/10.1210/jc.2016-2011, https://doi.org/10.1210/jc.2015-3901. PubMed DOI PMC

Dong WW, Zhang DL, Wang ZH, Lv CZ, Zhang P, Zhang H. Different types of diabetes mellitus and risk of thyroid cancer: A meta-analysis of cohort studies. Frontiers in Endocrinology. 2022;23:971213. doi: 10.3389/fendo.2022.971213. PubMed DOI PMC

Grimmichova T, Haluzik M, Vondra K, Matucha P, Hill M. Relations of prediabetes and type 2 diabetes to the thyroid cancer. Endocrine Connections. 2020;1:607–16. doi: 10.1530/EC-20-0180. PubMed DOI PMC

Fang M, Wang D, Coresh J, Selvin E. Undiagnosed Diabetes in U.S. Adults: Prevalence and Trends. Diabetes Care. 2022;1:1994–2002. doi: 10.2337/dc22-0242. PubMed DOI PMC

Fang Y, Zhang X, Xu H, Smith-Warner SA, Xu D, Fang H, Xu WH. Cancer risk in Chinese diabetes patients: a retrospective cohort study based on management data. Endocr Connect. 2018;7:1415–1423. doi: 10.1530/EC-18-0381. PubMed DOI PMC

Rezzónico JN, Rezzónico M, Pusiol E, Pitoia F, Niepomniszcze H. Increased prevalence of insulin resistance in patients with differentiated thyroid carcinoma. Metab Syndr. 2009;7:375–380. doi: 10.1089/met.2008.0062. PubMed DOI

Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol. 2020;10:107–111. doi: 10.2991/jegh.k.191028.001. PubMed DOI PMC

Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist. 2010;15:556–565. doi: 10.1634/theoncologist.2009-0285. PubMed DOI PMC

Kim SH, Park HS, Kim KH, Yoo H, Chae BJ, Bae JS, Jung SS. Correlation between obesity and clinicopathological factors in patients with papillary thyroid cancer. Surg Today. 2015;45:723–729. doi: 10.1007/s00595-014-0984-3. PubMed DOI

Ma J, Huang M, Wang L, Ye W, Tong Y, Wang H. Obesity and risk of thyroid cancer: evidence from a meta-analysis of 21 observational studies. Med Sci Monit. 2015;21:283–291. doi: 10.12659/MSM.892035. PubMed DOI PMC

Oberman B, Khaku A, Camacho F, Goldenberg D. Relationship between obesity, diabetes and the risk of thyroid cancer. Am J Otolaryng. 2015;36:535–541. doi: 10.1016/j.amjoto.2015.02.015. PubMed DOI

Farfel A, Kark JD, Derazne E, Tzur D, Barchana M, Lazar L, Afek A, et al. Predictors for thyroid carcinoma in Israel: a national cohort of 1,624,310 adolescents followed for up to 40 years. Thyroid. 2014;24:987–993. doi: 10.1089/thy.2013.0173. PubMed DOI

O’Neill RJ, Abd Elwahab S, Kerin MJ, Lowery AJ. Association of BMI with Clinicopathological Features of Papillary Thyroid Cancer: A Systematic Review and Meta-Analysis. World J Surg. 2021;45:2805–2815. doi: 10.1007/s00268-021-06193-2. PubMed DOI

Kaplan RM, Chambers DA, Glasgow RE. Big data and large sample size: a cautionary note on the potential for bias. Clin Transl Sci. 2014;7:342–346. doi: 10.1111/cts.12178. PubMed DOI PMC