The Evaluation of Pretreatment and Posttreatment Platelet/Lymphocyte and Neutrophil/Lymphocyte Ratios in Patients with Hyperthyroidism

Abstract

Background: Hyperthyroidism is defined as subnormal (usually undetectable) serum thyrotropin (TSH) with elevated serum levels of free triiodothyronine (free T3) and / or free thyroxine (free T4). Endogenous hyperthyroidism is most commonly due to Graves' disease (GD) or nodular thyroid disease. GD is an autoimmune disease that involves mostly the thyroid gland, the eyes and rarely the skin. The disease is generally recognized by symptoms related to hyperthyroidism. Anti-thyroid medications are used in its treatment, and these medications have anti-inflammatory features besides thyroid hormone synthesis. Thrombocyte/lymphocyte (TLR) and neutrophil/lymphocyte (NLR) rates are systemic inflammatory markers that are obtained from routine blood count, inexpensive and repeatable. It is aimed to evaluate the rates of TLR and NLR before and after treatment in hyperthyroidism.
Materials and Methods: The retrospective records of the patients who were admitted to Harran University Medical Faculty Endocrinology Polyclinic were examined, and patients who were diagnosed with hyperthyroidism and started medical treatment were included in the study. Patients with active infection and hemorrhagic pathology were excluded from the study. Laboratory results of the patients at the time of diagnosis and results after 3-6 months were evaluated. It was planned to compare NLR and TLR values before and after medical treatment.
Results: In the GD group, there was an increase in TSH, fT3, fT4 leukocyte, neutrophil, lymphocyte and hemoglobin levels before and after treatment, and this increase was statistically significant. Nevertheless, there was a significant increase in TSH, fT3, fT4 values in the toxic nodular goiter (TNG)/ multinodular goiter (MNG) group, while there was no significant difference in leukocyte, neutrophil, lymphocyte and hemoglobin levels before and after treatment. In the GD group, NLR of after treatment was significantly higher than before, but no significant difference was observed in the TLR.
Conclusions: GD, which is the most common cause of hyperthyroidism, can change hemotological parameters with various mechanisms. Antithyroid medications cause changes in blood count along with thyroid hormone levels.

Key words: 

Keywords

• Graves' disease

Hipertiroidi Hastalarında Tedavi Öncesi ve Sonrası Trombosit/Lenfosit ve Nötrofil/Lenfosit Oranlarının Değerlendirilmesi

Abstract

Amaç: Hipertiroidizm, yüksek serbest triiyodotironin (serbest T3) ve / veya serbest tiroksin düzeyleri (serbest T4) ile birlikte subnormal (genellikle saptanamayan) bir serum tirotropin (TSH) olarak tanımlanır. Endojen hipertiroidi en sık Graves hastalığı (GH) veya nodüler tiroid hastalığına bağlıdır. GH başta tiroid bezi olmak üzere, göz ve nadiren cildi tutan otoimmün bir hastalıktır. Hastalık genelde hipertiroidiye bağlı semptomlar ile tanınır. Tedavisinde anti-tiroid ilaçlar kullanılmakta olup, bu ilaçlar tiroid hormon sentezinin yanısıra anti-inflamatuar özelliklere de sahiptir. Trombosit/lenfosit (TLO) ve nötrofil/lenfosit (NLO) oranları ise rutin kan sayımından elde edilen, ucuz ve tekrarlanabilir, sistemik inflamasyon belirteçleridir. Hipertirodide tedavi öncesi ve tedavi sonrası TLO ve NLO’ nın değerlendirilmesi amaçlanmıştır.
Materyal ve Metod: Çalışmaya Harran Üniversitesi Tıp Fakültesi Endokrinoloji Polikliniği’ne başvuran hastaların geçmişe yönelik kayıtları incelenerek hipertiroidi tanısı alan ve medikal tedavi başlanan hastalar alındı. Aktif enfeksiyonu ve hematolojik patolojisi olan hastalar çalışmaya dahil edilmedi. Hastaların kayıtlarından tanı anındaki ve 3-6 ay sonraki laboratuvar sonuçları değerlendirildi. Medikal tedavi öncesi ve sonrası NLO ve TLO değerlerinin karşılaştırılması planlandı.
Bulgular: GH grubunda tedavi öncesi ve tedavi sonrası TSH, sT3, sT4, lökosit, nötrofil, lenfosit ve hemoglobin düzeylerinde artış vardı ve bu artış istatistiksel anlamlıydı. Bununla birlikte toksik nodüler guatr (TNG)/multınodüler guatr (MNG) grubunda TSH, sT3, sT4 değerlerinde anlamlı artış varken, lökosit, nötrofil, lenfosit ve hemoglobin düzeylerinde tedavi öncesi ve sonrası anlamlı bir fark yoktu. GH grubunda NLO tedavi sonrası öncesine göre anlamlı yüksekti ancak TLO’nda anlamlı fark gözlenmedi
Sonuç: Hipertiroidi özellikle en sık nedeni olan GH hemotolojik parametrelerde çeşitli mekanızmalarla değişiklik yapabilmektedir. Antitiroid ilaçlar tiroid hormon düzeyleriyle birlikte kan sayımında da değişikliklere neden olur

Keywords

• graves hastalığı,nötrofil lenfosit oranı,trombosit lenfosit oranı

References

1. Referans1 W.G. Kim, W.B. Kim, G. Woo, H. Kim, Y. Cho, T.Y. Kim, S.W. Kim, M.H. Shin, J.W. Park, H.L. Park, K. Oh, J.H. Chung, Thyroid stimulating hormone reference range and prevalence of thyroid dysfunction in the Korean population: Korea National Health and Nutrition Examination Survey. Endocrinol Metab.2017;32(1), 106–114.
2. Referans2 De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016Aug27;388(10047):906-918
3. Referans3 D.S. Ross, H.B. Burch, D.S. Cooper, M.C. Greenlee, P. Laurberg, A.L. Maia, et al. American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343–1421.
4. Referans4 Wémeau JL, Klein M, Sadoul JL, Briet C, Vélayoudom-Céphise FL. Graves' disease: Introduction, epidemiology, endogenous and environment alpathogenic factors. Ann. Endocrinol. 2018 Dec;79(6):599-607.
5. Referans5 Azab B, Bhatt VR, Phookan J, Murukutla S, Kohn N, Terjanian T, et al. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. AnnSurgOncol 2012;19:217–24.
6. Referans6 Kishi Y, Kopetz S, Chun YS, Palavecino M, Abdalla EK, Vauthey JN. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. AnnSurgOncol 2009;16:614–22.
7. Referans7 Wang S, Zhang Z, Fang F, Gao X, Sun W, Liu H. The neutrophil/lymphocyte ratio is an independent prognostic indicator in patients with bone metastasis. OncolLett. 2011;2:735–40.
8. Referans8 SeretisC, Gourgiotis S, Gemenetzis G, Seretis F, Lagoudianakis E, Dimitrakopoulos G. The significance of neutrophil/lymphocyte ratioas a possible marker of underlying papillary microcarcinomas in thyroidal goiters: a pilot study. Am J Surg 2013;205:691–6.

9. Referans9 Zhu Y, Si W, Sun Q, Qin B, Zhao W, Yang J. Platelet-lymphocyte ratio acts as an indicator of poor prognosis in patients with breast cancer. Oncotarget. 2017;8(1):1023–30.
10. Referans10 Prodromidou A, Andreakos P, Kazakos C, Vlachos DE, Perrea D, Pergialiotis V. The diagnostic efficacy of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in ovarian cancer. InflammRes. 2017;66(6):467–75.
11. Referans11 Idil Soylu A, Arikan Cortcu S, Uzunkaya F, Atalay YO, Bekci T, Gungor L, ve ark. The correlation of the platelet-to-lymphocyte ratio with the severity of stenosis and stroke in patients with carotid arterial disease. Vascular. 2017;25(3):299–306.
12. Referans12 Zhang M, Huang XZ, Song YX, Gao P, Sun JX, Wang ZN. High platelet-to-lymphocyte ratio predicts poor prognosis and clinicopathological characteristics in patients with breast cancer: a meta-analysis. BiomedResInt. 2017;9503025.
13. Referans13 F. Imtiaz, K. Shafique, S.S. Mirza, Z. Ayoob, P. Vart, S. Rao, Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int. Arch. Med 2012; 5(1):2.
14. Referans14 Buyukkaya E, Karakas MF, Karakas E, Akçay AB, Tanboga IH, Kurt M ve ark. Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome. ClinApplThrombHemost. 2014;20:159-63.
15. Referans15 Hamminga EA, van der Lely AJ, Neumann HA, Thio HB: Chronic inflammation in psoriasis and obesity: implications for therapy. MedHypotheses 2006;67:768-73.
16. Referans16 Turkmen K, Erdur FM, Ozcicek F, Ozcicek A, Akbas EM, Ozbicer A, ve ark. Platelet-to-lymphocyte ratio beter predicts inflammation than neutrophil-to-lymphocyte ratio in end-stage renal disease patients. HemodialInt 2013;17:391-6.
17. Referans17 Pozzilli P, Carotenuto P, Delitala G. Lymphocyti traffic and homing into target tissue and the generation of endocrine autoimmunity. Clinicalendocrinology. 1994; 41:545-554.
18. Referans18 Bagir G.S, Haydardedeoglu, F.E, Bakiner, O.S, Bozkirli, E, Ertorer, M.E. Mean Platelet Volume in Graves’ disease: A Sign of Hypermetabolism Rather than Autoimmunity?. Pak. J. Med. 2017;33(4):871-875.
19. Referans1 9 Li N. Platelet-lymphocyte cross-talk. J LeukocytBiol 2008; 83(5): 1069–1078.
20. Referans20 Turan E, Kaya A, Kulaksızoğlu M, Kandemir B, Erayman İ. Neutropenia Due to Very Long Time Propylthiouracil Usage in Toxic Multinodular Goiter. Turk J EndocrinolMetab 2016;20:16-18.
21. Referans21 Laurberg P. Remission of Graves' disease during anti-thyroid drug therapy. Time to reconsider the mechanism? Eur J Endocrinol. 2006 Dec;155(6):783-6.
22. Referans22 Roxburgh C.S., McMillan D.C. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. FutureOncol. 2010; 6(1):149-163.
23. Referans23 Bayir O, Karagoz T, Ocal B, Cakal E, Saylam G, Korkmaz M.H. Predictive role of neutrophil-lymphocyte and platelet-lymphocyte ratios in thyroid nodules with cytological diagnosis of “undetermined significance” and “suspicious for malignancy”. ENT Updates 2017;7(1):28-32.
24. Referans24 Kim S.M., Kim E.H., Kim B.H., Kim J.H., Park S.B., Nam Y.J., et al. Association of the Preoperative Neutrophil-to-ymphocyte Count Ratio and Platelet-to-Lymphocyte Count Ratio with Clinicopathological Characteristics in Patients with Papillary Thyroid Cancer. Endocrinol. Metab. (Seoul), 2015;30(4):494-501.
25. Referans25 Han S.W.,Kang S.Y., Kim S.K.,Youn H.J.,Jung S.H. Clinical significance of blood neutrophil-to-lymphocyte ratio in patients with papillary thyroid carcinoma. Korean J. Endocr. Surg. 2014;14:184-189.
26. Referans26 E. Turan, Evaluation of neutrophil-to-lymphocyte ratio and hematologic parameters in patients with Graves’ disease. Bratisl. Lekarskelisty. 2019;120(6):476–480.
27. Referans27 M. Dağdeviren, T. Akkan, D. Yapar, S. Karakaya, T. Dağdeviren, D. Ertuğrul, ve ark. Can neutrophil/lymphocyte ratio be used as an indicator of inflammation in patients with hyperthyroidism?. J Med Biochem. 2019; 38:1-6.
28. Referans28 D.L. Eakin, R.L. Peake, G.B. Weiss, Effect of therapy on theneutropenia of hyperthyroidism. South. Med. J. 1983;76(3):335–337, 340.
29. Referans29 N. Aggarwal, S.A. Tee, W. Saqib, T. Fretwell, G.P. Summerfield, S. Razvi, Treatment of hyperthyroidism with antithyroid drugs corrects mild neutropenia in Graves’ disease. Clin. Endocrinol. 2016;85(6);949–953.
30. Referans30 K. Van der Weerd, P.M. Van Hagen, B. Schrijver, D.J. Kwekkeboom, W.W. De Herder, M.R. Ten Broek, et al. The peripheral blood compartment in patients with Graves’ disease: activated T lymphocytes and increased transitional and pre-naive mature B lymphocytes. Clin. Exp. Immunol. 2013;174(2):256–264.
31. Referans31 Peng Y, Qi Y, Huang F, Chen X, Zhou Y, Ye L et al. Down-regulated resistin level in consequence of decreased neutrophi counts in untreated Grave’sdisease. Onco target 2016;7(48):78680–78687.
32. Referans32 Klatka M, Grywalska E, Surdacka A, Tarach J, Klatka J, Rolinski J. Peripheral blood lymphocyte apoptosis and its relationship with thyroid function tests in adolescents with hyperthyroidism due to Graves’ disease. ArchMedSci 2012;8(5):865–873.
33. Referans33 Mijin Kim, BoHyun Kim, MinHee Jang, Jeong Mi Kim, EunHeui Kim, Yun Kyung Jeon, et al. High neutrophil-to-lymphocyte ratio is associated with relapse in Graves’ disease after antithyroid drug therapy. Endocrine. 2020 Feb;67(2):406-411.
34. Referans34 H.C. Ford, J.M. Carter, The haematology of hyperthyroidism: abnormalities of erythrocytes, leucocytes, thrombocytes and haemostasis. Postgrad. Med. J. 1988; 64(756):735–742.
35. Referans35 D.S. Ross, H.B. Burch, D.S. Cooper, M.C. Greenlee, P. Laurberg, A.L. Maia, et al. American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343–1421.
36. Referans36 Hegazi M, Kumar R, Bitar Z, Ibrahim E. Pancytopenia related to Graves' disease. AnnSaudiMed 2008;28:48-9.