The relationship between Hashimoto's thyroiditis and vitamin D and the inflammatory marker platelet-to-lymphocyte ratio

Abstract

Aim: Hashimoto's thyroiditis (HT) is a chronic autoimmune-mediated disease that leads to overt hypothyroidism. Vitamin D is essential for immunity. This study examines possible impacts of vitamin D on the progression of HT and evaluates the use of platelet-lymphocyte ratio (PLR) as an indicator of its relationship with the inflammatory process. Material and Method: This is a retrospective case-control study, consisting of 60 individuals with HT and 40 healthy controls. Thyroid function tests, thyroid antibodies, vitamin D levels, erythrocyte sedimentation rate (ESR), parameters of complete blood count and C-reactive protein (CRP) levels were scanned retrospectively using participants' medical files between September 2018 and March 2019. Platelet count was divided by lymphocyte count to determine PLR. Results: HT patients had both considerably lower median vitamin D levels and higher percentages of vitamin D deficiency than the controls [12.08 (8.79–17.00) vs. 20.09 (20.00–34.00) and 80% vs. 22.5%, respectively, p<0.001). Vitamin D deficiency was also higher within the hypothyroid HT group than in the euthyroid HT group (p<0.001). The vitamin D levels of HT patients with subclinical hypothyroidism were lower than those with euthyroidism (p<0.004). The study groups showed no differences regarding CRP levels, higher levels of ESR were reported only in the overt hypothyroid patients (p=0.001), and higher PLRs were found in those euthyroid HT patients. Vitamin D was negatively correlated with TSH and anti-thyroid peroxidase (anti-TPO) levels (r=−0.294, p=0.023; r=−0.281, p=0.030, respectively). A positive correlation existed between TSH and anti-TPO (r=0.411, p=0.001) and ESR (r=0.365, p=0.002), but TSH and PLR were negatively correlated (r=−0.390, p=0.002). Conclusion: According to these findings, vitamin D may play a role in the transition to the hypothyroid phase in HT patients, and thus, vitamin D replacement may inhibit this progression. Moreover, our results indicate that PLR may not be a good inflammatory indicator for vitamin D-deficient HT patients.

Keywords

• Hashimoto
• vitamin D
• platelet lymphocyte ratio
• autoimmune thyroiditis
• hypothyroidism
• inflammation

References

1. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T (4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87: 489-99.
2. Huber G, Staub JJ, Meier C, et al. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab 2002; 87: 3221-6.
3. Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 2005; 26: 662-87.
4. Li HS, Verginis P, Carayanniotis G. Maturation of dendritic cells by necrotic thyrocytes facilitates induction of experimental autoimmune thyroiditis. Clin Exp Immunol 2006; 144: 467-74.
5. Jo E-K. Innate immunity to mycobacteria: vitamin D and autophagy. Cell Microbiol 2010; 12: 1026-35.
6. Wang J, Lv S, Chen G, et al. Meta-Analysis of the association between Vitamin D and autoimmune thyroid disease. Nutrients 2015; 7: 2485-98
7. Cvek M, Kaličanin D, Barić A, et al. Vitamin D and Hashimoto’s thyroiditis: observations from CROHT Biobank. Nutrients 2021; 13: 2793.
8. Botelho IMB, Moura Neto A, Silva CA, Tambascia MA, Alegre SM, Zantut-Wittmann DE. Vitamin D in Hashimoto’s thyroiditis and its relationship with thyroid function and inflammatory status. Endocr J 2018; 65: 1029-37.

9. Seo IH, Lee YJ. Usefulness of complete blood count (CBC) to assess cardiovascular and metabolic diseases in clinical aettings: a comprehensive literature review. Biomedicines 2022; 10: 2697.
10. Kocer D, Karakukcu C, Karaman H, Gokay F, Bayram F. May the neutrophil/lymphocyte ratio be a predictor in the differentiation of different thyroid disorders? Asian Pac J Cancer Prev 2015; 16: 3875-9.
11. Erge E, Kiziltunc C, Balci SB, et al. A novel Iinflammatory marker for the diagnosis of Hashimoto's thyroiditis: platelet-count-to-lymphocyte-count ratio. Diseases. 2023; 11: 15.
12. Cao YT, Zhang KY, Sun J, et al. Platelet abnormalities in autoimmune thyroid diseases: A systematic review and meta-analysis. Front Immunol 2022; 13: 1089469.
13. Onalan E, Donder E. Neutrophil, and platelet to lymphocyte ratio in patients with hypothyroid Hashimoto's thyroiditis. Acta Biomed 2020; 91: 310-4.
14. Bilge M, Yesilova A, Adas M, Helvaci A. Neutrophil- and platelet- to lymphocyte ratio in patients with euthyroid Hashimoto's thyroiditis. Exp Clin Endocrinol Diabetes 2019; 127: 545-9.
15. Sirbe C, Rednic S, Grama A, Pop TL. An update on the effects of Vitamin D on the immune system and autoimmune diseases. Int J Mol Sci 2022; 23: 9784.
16. Khozam SA, Sumaili AM, Alflan MA, Shawabkeh RAS. Association between vitamin D deficiency and autoimmune thyroid disorder: A systematic review. Cureus 2022; 14: e25869.
17. Volpe R. Autoimmune thyroiditis. In: Braverman LE, Utiger RD (eds) Werner and Ingbar’s The Thyroid, 6th ed Philadelphia: JB Lippincott Co.; 1991: 921–41.
18. Bottazzo GF, Pujol-Borrell R, Hanafusa T, Feldmann M. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet 12: 1115–9.
19. Inoue N, Watanabe M, Ishido N, et al. The functional polymorphisms of VDR, GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. Clin Exp Immunol 2014; 178: 262-9.
20. Yazici D, Yavuz D, Tarcin O, Sancak S, Deyneli O, Akalin S. Vitamin D receptor gene ApaI, TaqI, FokI and BsmI polymorphisms in a group of Turkish patients with Hashimoto's thyroiditis. Minerva Endocrinol 2013; 38: 195-201.
21. Tamer G, Arik S, Tamer I, Coksert D. Relative vitamin D insufficiency in Hashimoto's thyroiditis. Thyroid 2011; 21: 891-6.
22. Arslan-Suzen A. Hashimoto thyroiditis, vitamin D, active vitamin D, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio as an indicator of inflammation. Unpublished Ph D Thesis, Health Science University, Department of Internal Medicine, Ankara, 2018. https://tez.yok.gov.tr. (Accessed: 16.04.2023)
23. Dib PRB, Quirino-Teixeira AC, Merij LB, et al. Innate immune receptors in platelets and platelet-leukocyte interactions. Leukoc Biol 2020; 108: 1157-82.
24. Ito S, Fujiwara SI, Murahashi R, et al. Clinical association between thyroid disease and immune thrombocytopenia. Ann Hematol 2021; 100: 345-52.
25. Beyan C, Kaptan K. Reactive thrombocytosis accompanying subclinical hypothyroidism due to Hashimoto's thyroiditis. Blood Coagul Fibrinolysis 2013; 24: 649-51.
26. Deppermann C, Kubes P. Start a fire, kill the bug: The role of platelets in inflammation and infection. Innate immune 2018; 24: 335-48.
27. Kaushansky K. The molecular mechanisms that control thrombopoiesis. J Clin Invest 2005; 115: 3339-47.