ABSTRACT
Objectives:
Chronic lymphocytic leukemia is the most common type of leukemia seen in adults worldwide. Hashimoto’s thyroiditis is the most common form of autoimmune thyroid disease. Usually, there are high levels of thyroglobulin antibodies or thyroid peroxidase antibodies. Metabolic syndrome is also very common in the world and has become a public health problem threatening the world. Immune dysregulation in metabolic syndrome, chronic lymphocytic leukemia, and autoimmune thyroid diseases unites these diseases on a common denominator. Based on this common mechanism, we aimed to investigate the frequency of insulin resistance and thyroid autoantibodies in patients with early-stage chronic lymphocytic leukemia.
Materials and Methods:
Sixty-five early-stage chronic lymphocytic leukemia patients and 68 healthy controls were included in the study. Thyroid stimulating hormone, thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose and fasting insulin levels were measured in the patients and control groups. Statistical evaluation was performed using the Statistical Package for Social Sciences (SPSS) for Windows 20 (IBM SPSS Inc., Chicago, IL) program. The normal distribution of the data was evaluated with the Kolmogorov-Smirnov test. Normally distributed numerical variables were shown as mean ± standard deviation, while numerical variables not showing normal distribution were shown as median (minimum, maximum). P<0.05 (*) value was considered significant in statistical analysis.
Results:
Demographic and laboratory findings did not differ significantly between patients with chronic lymphocytic leukemia and those without thyroid dysfunction. The ratio of insulin resistance, thyroid dysfunction and thyroid antibodies in chronic lymphocytic leukemia and control groups did not differ significantly (p>0.05).
Conclusion:
It was observed that the frequency of insulin resistance and thyroid antibodies in early-stage chronic lymphocytic leukemia was not different from healthy controls.
Keywords:
Chronic Lymphocytic Leukemia, Insulin Resistance, Thyroid Antibodies, Metabolic Syndrome
References
1Redaelli A, Laskin BL, Stephens JM, et al. The clinical and epidemiological burden of chronic lymphocytic leukaemia. Eur J Cancer Care (Engl). 2004;13:279-287.
2Kipps TJ, Stevenson FK, Wu CJ, et al. Chronic lymphocytic leukaemia. Nat Rev Dis Primers. 2017;3:16096.
3Riches JC, Ramsay AG, Gribben JG. T-cell function in chronic lymphocytic leukaemia. Semin Cancer Biol. 2010;20:431-438.
4Beyer M, Kochanek M, Darabi K, et al. Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood. 2005;106:2018-2025.
5Giannopoulos K, Schmitt M, Kowal M, et al. Characterization of regulatory T cells in patients with B-cell chronic lymphocytic leukemia. Oncol Rep. 2008;20:677-682.
6Jadidi-Niaragh F, Ghalamfarsa G, Yousefi M, et al. Regulatory T cells in chronic lymphocytic leukemia: implication for immunotherapeutic interventions. Tumour Biol. 2013;34:2031-2039.
7 Lad DP, Varma S, Varma N, et al. Regulatory T-cell and T-helper 17 balance in chronic lymphocytic leukemia progression and autoimmune cytopenias. Leuk Lymphoma. 2015;56:2424-2428.
8Mao C, Wang S, Xiao Y, et al. Impairment of regulatory capacity of CD4+CD25+ regulatory T cells mediated by dendritic cell polarization and hyperthyroidism in Graves’ disease. J Immunol. 2011;186:4734-4743.
9Glick AB, Wodzinski A, Fu P, et al. Impairment of regulatory T-cell function in autoimmune thyroid disease. Thyroid. 2013;23:871-878.
10Raposo L, Martins S, Ferreira D, et al. Metabolic Syndrome, Thyroid Function and Autoimmunity - The PORMETS Study. Endocr Metab Immune Disord Drug Targets. 2019;19:75-83.
11Liu Y, Tang X, Tian J, et al. Th17/Treg cells imbalance and GITRL profile in patients with Hashimoto’s thyroiditis. Int J Mol Sci. 2014;15:21674-21686.
12Li C, Yuan J, Zhu YF, et al. Imbalance of Th17/Treg in Different Subtypes of Autoimmune Thyroid Diseases. Cell Physiol Biochem. 2016;40:245-252.
13 Chen WH, Chen YK, Lin CL, et al. Hashimoto’s thyroiditis, risk of coronary heart disease, and L-thyroxine treatment: a nationwide cohort study. J Clin Endocrinol Metab. 2015;100:109-114.
14He M, Zhang W, Dong Y, et al. Pro-inflammation NF-κB signaling triggers a positive feedback via enhancing cholesterol accumulation in liver cancer cells. J Exp Clin Cancer Res. 2017;36:15.
15Kassi E, Pervanidou P, Kaltsas G, et al. Metabolic syndrome: definitions and controversies. BMC Med. 2011;9:48.
16Zhou H, Liu F. Regulation, Communication, and Functional Roles of Adipose Tissue-Resident CD4+ T Cells in the Control of Metabolic Homeostasis. Front Immunol. 2018;9:1961.
17Kato I, Tajima K, Suchi T, et al. Chronic thyroiditis as a risk factor of B-cell lymphoma in the thyroid gland. Jpn J Cancer Res. 1985;76:1085-1090.
18Holm LE, Blomgren H, Löwhagen T. Cancer risks in patients with chronic lymphocytic thyroiditis. N Engl J Med. 1985;312:601-604.
19Tao L, Liu H, Gong Y. Role and mechanism of the Th17/Treg cell balance in the development and progression of insulin resistance. Mol Cell Biochem. 2019;459:183-188.
20Dimitriadis G, Baker B, Marsh H, et al. Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans. Am J Physiol. 1985;248:593-601.
21Dimitriadis G, Mitrou P, Lambadiari V, et al. Insulin action in adipose tissue and muscle in hypothyroidism. J Clin Endocrinol Metab. 2006;91:4930-4937.
22 Liu J, Duan Y, Fu J et al. Association between thyroid hormones, thyroid antibodies, and cardiometabolic factors in non-obese individuals with normal thyroid function. Front Endocrinol (Lausanne) 2018;9:130.
23Fabbrini E, Cella M, McCartney SA, et al Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology. 2013;145:366-374.
24O’Rourke RW, Lumeng CN. Obesity heats up adipose tissue lymphocytes. Gastroenterology. 2013;145:282-285.
25Chuang HC, Sheu WH, Lin YT, et al. HGK/MAP4K4 deficiency induces TRAF2 stabilization and Th17 differentiation leading to insulin resistance. Nat Commun. 2014;5:4602.
26Vitales-Noyola M, Ramos-Levi AM, Martínez-Hernández R, et al. Pathogenic Th17 and Th22 cells are increased in patients with autoimmune thyroid disorders. Endocrine. 2017;57:409-417.
27Giordano C, Stassi G, De Maria R, et al. Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto’s thyroiditis. Science. 1997;275:960-963.
28Beyan C, Kaptan K, Ifran A. Coexistence of chronic lymphocytic leukemia and Hashimoto’s thyroiditis. Ann Hematol. 2006;85:811-812.
29Zhou YP, Pena JC, Roe MW, et al. Overexpression of Bcl-x(L) in beta-cells prevents cell death but impairs mitochondrial signal for insulin secretion. Am J Physiol Endocrinol Metab. 2000;278:340-351.
30Luciani DS, White SA, Widenmaier SB, et al. Bcl-2 and Bcl-xL suppress glucose signaling in pancreatic β-cells. Diabetes. 2013;62:170-182.
31Ougolkov AV, Bone ND, Fernandez-Zapico ME, et al. Inhibition of glycogen synthase kinase-3 activity leads to epigenetic silencing of nuclear factor kappaB target genes and induction of apoptosis in chronic lymphocytic leukemia B cells. Blood. 2007;110:735-742.
32Larsson SC, Wolk A. Overweight and obesity and incidence of leukemia: a meta-analysis of cohort studies. Int J Cancer. 2008;122:1418-1421.
33Pothiwala P, Jain SK, Yaturu S. Metabolic syndrome and cancer. Metab Syndr Relat Disord. 2009;7:279-288.
34Cowey S, Hardy RW. The metabolic syndrome: A high-risk state for cancer? Am J Pathol. 2006;169:1505-1522.
35Henriksen EJ, Dokken BB. Role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes. Curr Drug Targets. 2006;7:1435-1441.
36Rebolleda N, Losada-Fernandez I, Perez-Chacon G, et al. Synergistic Activity of Deguelin and Fludarabine in Cells from Chronic Lymphocytic Leukemia Patients and in the New Zealand Black Murine Model. PLoS One. 2016;11:0154159.
37Kulikov R, Boehme KA, Blattner C. Glycogen synthase kinase 3-dependent phosphorylation of Mdm2 regulates p53 abundance. Mol Cell Biol. 2005;25:7170-7180.
