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Published in: Endocrine 2/2020

01-02-2020 | Hyperthyroidism | Original Article

High neutrophil-to-lymphocyte ratio is associated with relapse in Graves’ disease after antithyroid drug therapy

Authors: Mijin Kim, Bo Hyun Kim, Min Hee Jang, Jeong Mi Kim, Eun Heui Kim, Yun Kyung Jeon, Sang Soo Kim, In Joo Kim

Published in: Endocrine | Issue 2/2020

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Abstract

Purpose

Antithyroid drugs (ATDs) are effective in controlling hyperthyroidism due to Graves’ disease (GD); however, long-term remission rates are low. The neutrophil-to-lymphocyte ratio (NLR) is a useful prognostic marker in many inflammatory diseases. We aimed to evaluate whether NLR can be used as a prognostic marker for relapse in patients with GD after ATD therapy.

Methods

This retrospective cohort study included 108 patients with newly diagnosed GD who achieved remission after ATD therapy and were followed-up for >12 months after ATD discontinuation. The primary outcome was relapse-free survival (RFS).

Results

Patients were classified into two groups according to baseline NLR: low NLR group with NLR < 1.14 (n = 59; 55%) and high NLR group with NLR ≥ 1.14 (n = 49; 45%). During the median follow-up of 6.5 years, disease relapse after a year of ATD withdrawal occurred in 23 (21%) patients. The patients with high NLR had poorer RFS than those with low NLR, and RFS curves were significantly different between the two groups (p = 0.002). In multivariate analysis, a high NLR (OR = 4.22, p = 0.016) was an independent prognostic factor for relapse in patients with GD after adjusting for age, sex, goiter, orbitopathy, thyroid hormone levels, thyrotropin binding inhibiting immunoglobulin titer, and the duration of ATD therapy.

Conclusions

This study showed that NLR can be an early and cost-effective prognostic biomarker for relapse in patients with GD after ATD therapy. Further studies are needed to validate the prognostic role of NLR in GD.
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Literature
1.
go back to reference D.S. Ross, H.B. Burch, D.S. Cooper, M.C. Greenlee, P. Laurberg, A.L. Maia, S.A. Rivkees, M. Samuels, J.A. Sosa, M.N. Stan, M.A. Walter, 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 26(10), 1343–1421 (2016). https://doi.org/10.1089/thy.2016.0229 CrossRefPubMed D.S. Ross, H.B. Burch, D.S. Cooper, M.C. Greenlee, P. Laurberg, A.L. Maia, S.A. Rivkees, M. Samuels, J.A. Sosa, M.N. Stan, M.A. Walter, 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 26(10), 1343–1421 (2016). https://​doi.​org/​10.​1089/​thy.​2016.​0229 CrossRefPubMed
2.
go back to reference 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 2013 to 2015. Endocrinol. Metab. 32(1), 106–114 (2017). https://doi.org/10.3803/EnM.2017.32.1.106 CrossRef 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 2013 to 2015. Endocrinol. Metab. 32(1), 106–114 (2017). https://​doi.​org/​10.​3803/​EnM.​2017.​32.​1.​106 CrossRef
4.
go back to reference K.H. Yi, J.H. Moon, I.-J. Kim, H.-S. Bom, J. Lee, W.Y. Chung, J.H. Chung, Y.K. Shong, The diagnosis and management of hyperthyroidism consensus—report of the Korean thyroid association. J. Korean Thyroid Assoc. 6(1), 1–11 (2013)CrossRef K.H. Yi, J.H. Moon, I.-J. Kim, H.-S. Bom, J. Lee, W.Y. Chung, J.H. Chung, Y.K. Shong, The diagnosis and management of hyperthyroidism consensus—report of the Korean thyroid association. J. Korean Thyroid Assoc. 6(1), 1–11 (2013)CrossRef
10.
go back to reference A.J. Templeton, M.G. McNamara, B. Seruga, F.E. Vera-Badillo, P. Aneja, A. Ocana, R. Leibowitz-Amit, G. Sonpavde, J.J. Knox, B. Tran, I.F. Tannock, E. Amir, Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J. Natl Cancer Inst. 106(6), dju124 (2014). https://doi.org/10.1093/jnci/dju124 CrossRefPubMed A.J. Templeton, M.G. McNamara, B. Seruga, F.E. Vera-Badillo, P. Aneja, A. Ocana, R. Leibowitz-Amit, G. Sonpavde, J.J. Knox, B. Tran, I.F. Tannock, E. Amir, Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J. Natl Cancer Inst. 106(6), dju124 (2014). https://​doi.​org/​10.​1093/​jnci/​dju124 CrossRefPubMed
11.
go back to reference A. Kucuk, A.U. Uslu, Y. Ugan, S. Bagcaci, A.Y. Karahan, A. Akarmut, A. Sahin, S. Kucuksen, Neutrophil-to-lymphocyte ratio is involved in the severity of ankylosing spondylitis. Bratisl. Lekarske Listy 116(12), 722–725 (2015) A. Kucuk, A.U. Uslu, Y. Ugan, S. Bagcaci, A.Y. Karahan, A. Akarmut, A. Sahin, S. Kucuksen, Neutrophil-to-lymphocyte ratio is involved in the severity of ankylosing spondylitis. Bratisl. Lekarske Listy 116(12), 722–725 (2015)
12.
go back to reference Z.A. Ozturk, M.E. Kuyumcu, Y. Yesil, E. Savas, H. Yildiz, Y. Kepekci, S. Ariogul, Is there a link between neutrophil-lymphocyte ratio and microvascular complications in geriatric diabetic patients? J. Endocrinol. Investig. 36(8), 593–599 (2013). https://doi.org/10.3275/8894 CrossRef Z.A. Ozturk, M.E. Kuyumcu, Y. Yesil, E. Savas, H. Yildiz, Y. Kepekci, S. Ariogul, Is there a link between neutrophil-lymphocyte ratio and microvascular complications in geriatric diabetic patients? J. Endocrinol. Investig. 36(8), 593–599 (2013). https://​doi.​org/​10.​3275/​8894 CrossRef
15.
go back to reference World Health Organization. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers, 3rd ed. (2007). World Health Organization. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers, 3rd ed. (2007).
16.
go back to reference L. Bartalena, L. Baldeschi, A.J. Dickinson, A. Eckstein, P. Kendall-Taylor, C. Marcocci, M.P. Mourits, P. Perros, K. Boboridis, A. Boschi, N. Curro, C. Daumerie, G.J. Kahaly, G. Krassas, C.M. Lane, J.H. Lazarus, M. Marino, M. Nardi, C. Neoh, J. Orgiazzi, S. Pearce, A. Pinchera, S. Pitz, M. Salvi, P. Sivelli, M. Stahl, G. von Arx, W.M. Wiersinga, Consensus statement of the European group on Graves’ orbitopathy (EUGOGO) on management of Graves’ orbitopathy. Thyroid. 18(3), 333–346 (2008). https://doi.org/10.1089/thy.2007.0315 CrossRefPubMed L. Bartalena, L. Baldeschi, A.J. Dickinson, A. Eckstein, P. Kendall-Taylor, C. Marcocci, M.P. Mourits, P. Perros, K. Boboridis, A. Boschi, N. Curro, C. Daumerie, G.J. Kahaly, G. Krassas, C.M. Lane, J.H. Lazarus, M. Marino, M. Nardi, C. Neoh, J. Orgiazzi, S. Pearce, A. Pinchera, S. Pitz, M. Salvi, P. Sivelli, M. Stahl, G. von Arx, W.M. Wiersinga, Consensus statement of the European group on Graves’ orbitopathy (EUGOGO) on management of Graves’ orbitopathy. Thyroid. 18(3), 333–346 (2008). https://​doi.​org/​10.​1089/​thy.​2007.​0315 CrossRefPubMed
19.
go back to reference R. Zahorec, Ratio of neutrophil to lymphocyte counts–rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl. Lekarske Listy 102(1), 5–14 (2001) R. Zahorec, Ratio of neutrophil to lymphocyte counts–rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl. Lekarske Listy 102(1), 5–14 (2001)
24.
go back to reference K. Van der Weerd, P.M. Van Hagen, B. Schrijver, D.J. Kwekkeboom, W.W. De Herder, M.R. Ten Broek, P.T. Postema, J.J. Van Dongen, F.J. Staal, W.A. Dik, The peripheral blood compartment in patients with Graves’ disease: activated T lymphocytes and increased transitional and pre-naive mature B lymphocytes. Clin. Exp. Immunol. 174(2), 256–264 (2013). https://doi.org/10.1111/cei.12183 CrossRefPubMedPubMedCentral K. Van der Weerd, P.M. Van Hagen, B. Schrijver, D.J. Kwekkeboom, W.W. De Herder, M.R. Ten Broek, P.T. Postema, J.J. Van Dongen, F.J. Staal, W.A. Dik, The peripheral blood compartment in patients with Graves’ disease: activated T lymphocytes and increased transitional and pre-naive mature B lymphocytes. Clin. Exp. Immunol. 174(2), 256–264 (2013). https://​doi.​org/​10.​1111/​cei.​12183 CrossRefPubMedPubMedCentral
27.
go back to reference B. McIver, J.C. Morris, The pathogenesis of Graves’ disease. Endocrinol. Metab. Clin. North Am. 27(1), 73–89 (1998)CrossRef B. McIver, J.C. Morris, The pathogenesis of Graves’ disease. Endocrinol. Metab. Clin. North Am. 27(1), 73–89 (1998)CrossRef
33.
go back to reference B.G. Nedrebo, P.I. Holm, S. Uhlving, J.I. Sorheim, S. Skeie, G.E. Eide, E.S. Husebye, E.A. Lien, S. Aanderud, Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves’ disease. Eur. J. Endocrinol. 147(5), 583–589 (2002)CrossRef B.G. Nedrebo, P.I. Holm, S. Uhlving, J.I. Sorheim, S. Skeie, G.E. Eide, E.S. Husebye, E.A. Lien, S. Aanderud, Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves’ disease. Eur. J. Endocrinol. 147(5), 583–589 (2002)CrossRef
Metadata
Title
High neutrophil-to-lymphocyte ratio is associated with relapse in Graves’ disease after antithyroid drug therapy
Authors
Mijin Kim
Bo Hyun Kim
Min Hee Jang
Jeong Mi Kim
Eun Heui Kim
Yun Kyung Jeon
Sang Soo Kim
In Joo Kim
Publication date
01-02-2020
Publisher
Springer US
Published in
Endocrine / Issue 2/2020
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-019-02137-y

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