Diyabetik Hastalarda Tiroid Kanserlerinin Klinikopatolojik Özellikleri Non-diyabetik Hastalardan Farklı mıdır?

Amaç: Diyabetes mellitus ve tiroid kanseri arasında ilişki olup olmadığı ile ilgili yapılmış çok sayıda çalışma olmasına rağmen diyabetik hastalardaki tiroid kanserinin klinikopatolojik özellikleri ile ilgili çok az sayıda çalışma mevcuttur. Bu çalışmadaki amacımız diyabetik hastalarda malign nodüllerin ultrasonografik özellikler, sitolojik özellikler ve tiroid kanseri tiplerinin dağılımı açısından non-diyabetik hastalara göre farklılık olup olmadığının tespit edilmesidir.        Materyal ve Metot: 2007-2014 yılları arasında tiroidektomi yapılan hastalar retrospektif olarak tarandı. Sitolojik ve histopatolojik verileri tam olan hastalar çalışmaya dahil edildi. Hastalar diyabetik ve non-diyabetik olarak ayrıldı. Demografik, hormonal, ultrasonografik, sitolojik ve histopatolojik özellikler karşılaştırıldı.Bulgular: Toplam 865 hastanın 113’ü diyabetikti (% 13,06). Diyabetiklerde yaş ortancası daha fazlaydı [59 (25-81), 48 (19-84); p<0,001]. Tiroid stimülan hormon (TSH) düzeyi, anti-tiroid peroksidaz ve anti-tiroglobulin pozitifliği ve nodül sayısı benzerdi (sırasıyla p=0,849; p=0,268, p=0,168 ve p=0,054). Multifokalite oranı diyabetiklerde daha fazlaydı (% 45,13 ve % 31,38, p=0,004). Uzak metastazı olan tek hasta, diyabetik gruptaydı. Malign nodüllerin ultrasonografik incelemesinde; nodül boyutları, ekojenite, nodül yapısı, ön-arka çap/transvers çap oranı ve hipoekoik halo varlığı benzerdi. Makrokalsifikasyon ve sınır düzensizliği oranı diyabetiklerde daha fazlaydı (sırası ile; % 45,98 ve % 31,83, p=0,010; % 80,46 ve % 61,48, p=0,001). Mikrokalsifikasyon oranı anlamlılık sınırındaydı (% 55,17 ve % 43,88, p=0,050). Malign nodüllerin sitolojisi incelendiğinde diyabetiklerde non-diyabetiklere göre malignite şüphesi oranı belirgin az, malignite oranı 2 kat fazlaydı. Histopatolojide tiroid kanseri tipleri dağılımında farklılık yoktu ve her iki grupta da en sık kanser tipi papiller tiroid kanseri (PTK) idi. Diyabetik hastalarda klasik varyant PTK oranı belirgin yüksek, folliküler varyant oranı belirgin düşüktü. Mikrokarsinom oranı diyabetik grupta belirgin fazlaydı (p=0,046). Lenfovasküler invazyon, kapsüler invazyon, ekstratiroidal yayılım açısından fark yoktu.Sonuç: Diyabetik hastalarda tiroid kanseri tiplerinin dağılımı non-diyabetik hastalarla benzerdir ve PTK varyant dağılımı dışındaki histopatolojik özellikler farklılık göstermemektedir. Multifokalite oranı diyabetik hastalarda non-diyabetiklere göre daha fazladır. Diyabetiklerde tiroid kanserinin seyrini değerlendirmek için takip verilerinin olduğu ileri çalışmalara ihtiyaç vardır.

Are There Any Differences in Clinicopathological Features of Thyroid Cancer Between Diabetic and Non-Diabetic Patients?

Objectives: Although there are numerous studies about the relationship between diabetes mellitus and thyroid cancer, there are few studies about the clinicopathological features in diabetic patients with thyroid cancer. Our aim is to evaluate whether ultrasonographic and cytopathological features of malignant nodules and distribution of thyroid cancer and its variants are different in diabetic and non-diabetic patients. Materials and Methods: Data of patients who underwent thyroidectomy between 2007-2014 were reviewed retrospectively. Patients with cyto-histopathological data were included. Hormonal, ultrasonographic, and cyto-histopathologic features of diabetic and non-diabetic patients were compared.        Results: Of 865 patients, 113 were diabetic (13.06%). Median age was higher in diabetic patients [59 (25-81) years, 48 (19-84) years; p<0.001]. TSH level, anti-TPO and anti-TG autoantibody positivity and number of nodules were similar between groups (p=0.849, 0.268, 0.168, 0.054). Frequency of multifocality was higher in diabetics (45.13% vs 31.38%, p=0.004). The only patient with metastatic disease was in diabetic group. In ultrasonographic evaluation of malignant nodules; dimension, echogenity, texture, anteroposterior/transverse dimension, and presence of halo were similar in two groups. Rates of macrocalcification and presence of irregular margin were higher in diabetic patients (46% vs 31.8%, p=0.01; 80.5% vs 61,5%, p=0.001; respectively). Rate of microcalcification was in limit of significance (55.17% vs 43.88%, p=0.05). Frequency of suspicious for malignancy was significantly lower, and rate of malignancy was two times higher in cytologic evaluation of malignant nodules of diabetic patients compared to those of non-diabetic ones. In histopathologic evaluation, there was no difference in distribution of the type of thyroid cancer. Furthermore, the most frequent thyroid cancer was papillary thyroid cancer (PTC) in two groups. The classical variant of PTC was significantly higher, but follicular variant of PTC was significantly lower in diabetic group. Microcarcinoma rate was significantly higher in diabetic group (p=0.046). Rates of lymphovascular invasion, capsular invasion and extrathyroidal extension were similar in both groups.  Conclusion: Distribution of the type of thyroid cancer and histopathological features, except variants of PTC, were similar in diabetic and non-diabetic patients. Rate of multifocality and microcarcinoma were higher in diabetic patients compared to non-diabetic ones. Further researches with follow-up data are needed to evaluate the course of thyroid cancer in diabetic patients.

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  • Kilfoy BA, Zheng T, Holford TR, et al. International patterns and trends in thyroid cancer incidence, 1973-2002. Cancer Causes Control. 2009;20(5):525-31.
  • Busco S, Paolo GR, Isabella S, Pezzotti P, Buzzoni C, Pannozzo F. Increased incidence of thyroid cancer in Latina, Italy: A possible role of detection of subclinical disease. Cancer Epidemiol 2013;37:262-9.
  • Yeo Y, Ma SH, Hwang Y, et al. Diabetes mellitus and risk of thyroid cancer: a meta-analysis. PLoS One 2014;9(6):e98135.
  • Nagataki S, Nyström E. Epidemiology and primary prevention of thyroid cancer. Thyroid 2002;12(10):889-96.
  • Satman I, Omer B, Tutuncu Y, et al. TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. Eur J Epidemiol. 2013;28(2):169-80.
  • Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care 2010;33:1674-85.
  • Tseng CH. Diabetes, metformin use, and colon cancer: A population based cohort study in Taiwan. Eur J Endocrinol 2012;167:409-16.
  • Li H, Qian J. Association of diabetes mellitus with thyroid cancer risk: A meta-analysis of cohort studies. Medicine (Baltimore). 2017;96(47):e8230.
  • Lo SF, Chang SN, Muo CH, et al. Modest increase in risk of specific types of cancer types in type 2 diabetes mellitus patients. Int J Cancer 2013;132:182-8.
  • Tulinius H, Sigfusson N, Sigvaldason H, Bjarnadóttir K, Tryggvadóttir L. Risk factors for malignant diseases: a cohort study on a population of 22,946 Icelanders. Cancer Epidemiol Biomarkers Prev 1997;6:863-73.
  • Hemminki K, Li X, Sundquist J, Sundquist K. Risk of cancer following hospitalization for type 2 diabetes. Oncologist 2010;15:548-55.
  • Aschebrook-Kilfoy B, Sabra MM, Brenner A. Diabetes and Thyroid Cancer Risk in the National Institutes of Health-AARP Diet and Health Study. Thyroid 2011;21:957-63.
  • Meinhold CL, Ron E, Schonfeld SJ, et al. Nonradiation Risk Factors for Thyroid Cancer in the US Radiologic Technologists Study. American Journal of Epidemiology 2009;171:242-52.
  • Chen S-T, Hsueh C, Chiou W-K, Lin J-D. Disease-Specific Mortality and Secondary Primary Cancer in Well-Differentiated Thyroid Cancer with Type 2 Diabetes Mellitus. PLoS ONE 2013;8(1):e55179.
  • Tseng CH. Diabetes and thyroid cancer mortality: a 12-year prospective follow-up of Taiwanese. Eur J Clin Invest 2013;43(6):595-601.
  • Atchison EA, Gridley G, Carreon JD, Leitzmann MF, McGlynn KA. Risk of cancer in a large cohort of U.S. veterans with diabetes. Int J Cancer 2011;128:635–43.
  • Meinhold CL, Ron E, Schonfeld SJ, et al. Nonradiation risk factors for thyroid cancer in the US Radiologic Technologists Study. Am J Epidemiol 2010;171:242-52.
  • Wideroff L, Gridley G, Mellemkjaer L, et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetesmellitus in Denmark. J Natl Cancer Inst 1997;89:1360-5.
  • Balasubramaniam S, Ron E, Gridley G, Schneider AB, Brenner AV. Association between benign thyroid and endocrine disorders and subsequent risk of thyroid cancer among 4.5 million U.S. male veterans. J Clin Endocrinol Metab 2012;97:2661-9.
  • Kitahara CM, Platz EA, Beane Freeman LE, et al. Physical activity, diabetes, and thyroid cancer risk: a pooled analysis of five prospective studies. Cancer Causes Control 2012;23:463-71.
  • Chodick G, Heymann AD, Rosenmann L, et al. Diabetes and risk of incident cancer: a large population-based cohort study in Israel. Cancer Causes Control 2010;21:879- 87.
  • Almquist M, Johansen D, Björge T, et al. Metabolic factors and risk of thyroid cancer in the Metabolic syndrome and Cancer project (Me-Can). Cancer Causes Control 2011;22:743-51.
  • Luo J, Phillips L, Liu S, Wactawski-Wende J, Margolis KL. Diabetes, diabetes treatment, and risk of thyroid cancer. J Clin Endocrinol Metab. 2016;101(3):1243-8.
  • Chen GG, Vlantis AC, Zeng Q, van Hasselt CA. Regulation of cell growth by estrogen signaling and potential targets in thyroid cancer. Curr Cancer Drug Targets 2008;8:367-77.
  • Tseng CH. Thyroid cancer risk is not increased in diabetic patients. PLoS One 2012;7:e53096.
  • Tseng CH. Sitagliptin use and thyroid cancer risk in patients with type 2 diabetes. Oncotarget 2016;7(17):24871-9.
  • 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.
  • Paulus YM, Riedel ER, Sabra MM, Tuttle RM, Kalin MF. Prevalence of diabetes mellitus in patients with newly evaluated papillary thyroid cancer. Thyroid Res 2014;7:7.
  • Zivaljevic V, Vlajinac H, Jankovic R, Marinkovic J, Diklic A, Paunovic I. Case-control study of anaplastic thyroid cancer. Tumori 2004;90:9-12.
  • Jung K-W, Park S, Kong H-J, et al. Cancer Statistics in Korea: Incidence, Mortality and Survival in 2006-2007. J Korean Med Sci 2010;25:1113.
  • Tseng CH. Diabetes and thyroid cancer mortality: a 12-year prospective follow-up of Taiwanese. Eur J Clin Invest 2013;43(6):595-601. Yan Y, Hu F, Wu W, Ma R, Huang H. Expression characteristics of proteins of IGF-1R, p-Akt, and survivin in papillary thyroid carcinoma patients with type 2 diabetes mellitus. Medicine (Baltimore). 2017;96(12):e6393.