open access

Vol 72, No 1 (2021)
Original paper
Published online: 2020-09-18
Submitted: 2020-06-01
Accepted: 2020-08-28
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The association of TSH-receptor antibody with the clinical and laboratory parameters in patients with newly diagnosed Graves’ hyperthyroidism: experience from a tertiary referral center including a large number of patients with TSH-receptor antibody-negative patients with Graves’ hyperthyroidism

Sayid Shafi Zuhur, Ogun Bilen, Hunkar Aggul, Birol Topcu, Aliye Celikkol, Gulsah Elbuken
DOI: 10.5603/EP.a2020.0062
·
Pubmed: 32944926
·
Endokrynologia Polska 2021;72(1):14-21.

open access

Vol 72, No 1 (2021)
Original Paper
Published online: 2020-09-18
Submitted: 2020-06-01
Accepted: 2020-08-28

Abstract

Introduction: Although the TSH-receptor antibody (TRAb) plays a central role in the pathogenesis of Graves’ disease (GD), the association between TRAb at first diagnosis and clinical and laboratory parameters is not well known. On the other hand, a minority of patients with GD may be TRAb negative, and there is a lack of adequate evidence to demonstrate the clinical and laboratory characteristics of these patients. Therefore, we aimed to investigate the association of TRAb at the initial diagnosis of GD with the clinical and laboratory parameters in a large number of patients with GD and to compare the clinical and laboratory parameters between patients with high TRAb levels and TRAb-negative patients.

Material and methods: This study included 440 patients [326 (74%) female, 114 (26%) male]. All patients were classified according to gender, age, smoking habit, and TRAb levels.

Results: TRAb levels were significantly higher in male compared to female patients and in smokers compared to non-smokers. Smoking male patients had the highest TRAb levels. In regression analysis, goiter size, male gender, cigarette smoking, Graves’ orbitopathy, fT3, and anti-TPO antibody levels were independently associated with high TRAb levels, while age at diagnosis and fT4 levels were not independently associated with high TRAb levels. TRAb-negative GD was diagnosed in 80 (18%) patients. TRA-negative patients had markedly less severe clinical and laboratory hyperthyroidism compared to patients with high TRAb levels. Moreover, the smoking habit was significantly lower in patients with TRAb-negative GD.

Conclusions: According to our study results, TRAb levels at the initial diagnosis of GD are differently associated with clinical and laboratory parameters. Male patients and smoking patients with GD tended to have markedly higher TRAb levels and more severe clinical hyperthyroidism. Therefore, besides other contributing factors, male gender and smoking may affect TRAb levels and consequently the severity of hyperthyroidism in patients with GD. Furthermore, male gender and smoking may have a synergistic effect on TRAb levels and consequently on the severity of hyperthyroidism in patients with GD.

Abstract

Introduction: Although the TSH-receptor antibody (TRAb) plays a central role in the pathogenesis of Graves’ disease (GD), the association between TRAb at first diagnosis and clinical and laboratory parameters is not well known. On the other hand, a minority of patients with GD may be TRAb negative, and there is a lack of adequate evidence to demonstrate the clinical and laboratory characteristics of these patients. Therefore, we aimed to investigate the association of TRAb at the initial diagnosis of GD with the clinical and laboratory parameters in a large number of patients with GD and to compare the clinical and laboratory parameters between patients with high TRAb levels and TRAb-negative patients.

Material and methods: This study included 440 patients [326 (74%) female, 114 (26%) male]. All patients were classified according to gender, age, smoking habit, and TRAb levels.

Results: TRAb levels were significantly higher in male compared to female patients and in smokers compared to non-smokers. Smoking male patients had the highest TRAb levels. In regression analysis, goiter size, male gender, cigarette smoking, Graves’ orbitopathy, fT3, and anti-TPO antibody levels were independently associated with high TRAb levels, while age at diagnosis and fT4 levels were not independently associated with high TRAb levels. TRAb-negative GD was diagnosed in 80 (18%) patients. TRA-negative patients had markedly less severe clinical and laboratory hyperthyroidism compared to patients with high TRAb levels. Moreover, the smoking habit was significantly lower in patients with TRAb-negative GD.

Conclusions: According to our study results, TRAb levels at the initial diagnosis of GD are differently associated with clinical and laboratory parameters. Male patients and smoking patients with GD tended to have markedly higher TRAb levels and more severe clinical hyperthyroidism. Therefore, besides other contributing factors, male gender and smoking may affect TRAb levels and consequently the severity of hyperthyroidism in patients with GD. Furthermore, male gender and smoking may have a synergistic effect on TRAb levels and consequently on the severity of hyperthyroidism in patients with GD.

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Keywords

Graves’ disease; hyperthyroidism; TRAb; TRAb-negative; smoking

About this article
Title

The association of TSH-receptor antibody with the clinical and laboratory parameters in patients with newly diagnosed Graves’ hyperthyroidism: experience from a tertiary referral center including a large number of patients with TSH-receptor antibody-negative patients with Graves’ hyperthyroidism

Journal

Endokrynologia Polska

Issue

Vol 72, No 1 (2021)

Article type

Original paper

Pages

14-21

Published online

2020-09-18

DOI

10.5603/EP.a2020.0062

Pubmed

32944926

Bibliographic record

Endokrynologia Polska 2021;72(1):14-21.

Keywords

Graves’ disease
hyperthyroidism
TRAb
TRAb-negative
smoking

Authors

Sayid Shafi Zuhur
Ogun Bilen
Hunkar Aggul
Birol Topcu
Aliye Celikkol
Gulsah Elbuken

References (30)
  1. Brent GA. Clinical practice. Graves' disease. N Engl J Med. 2008; 358(24): 2594–2605.
  2. Bartalena L. Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol. 2013; 9(12): 724–734.
  3. Rapoport B, Chazenbalk GD, Jaume JC, et al. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr Rev. 1998; 19(6): 673–716.
  4. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016; 26(10): 1343–1421.
  5. Kahaly GJ, Bartalena L, Hegedüs L, et al. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism. Eur Thyroid J. 2018; 7(4): 167–186.
  6. Arnson Y, Shoenfeld Y, Amital H. Effects of tobacco smoke on immunity, inflammation and autoimmunity. J Autoimmun. 2010; 34(3): J258–J265.
  7. Wiersinga WM. Smoking and thyroid. Clin Endocrinol (Oxf). 2013; 79(2): 145–151.
  8. Vestergaard P. Smoking and thyroid disorders--a meta-analysis. Eur J Endocrinol. 2002; 146(2): 153–161.
  9. Yoshioka W, Miyauchi A, Ito M, et al. Kinetic analyses of changes in serum TSH receptor antibody values after total thyroidectomy in patients with Graves' disease. Endocr J. 2016; 63(2): 179–185.
  10. Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol. 2014; 35(3): 347–369.
  11. Zuhur SS, Yildiz I, Altuntas Y, et al. The effect of gender on response to antithyroid drugs and risk of relapse after discontinuation of the antithyroid drugs in patients with Graves' hyperthyroidism: a multicentre study. Endokrynol Pol. 2020; 71(3): 207–212.
  12. Zuhur SS, Elbuken G, Yildiz I, et al. External Validation of the GREAT Score in Turkish Patients with Graves' Hyperthyroidism Treated with the Titration Regimen Method of Antithyroid Drugs: A Multicenter Study. Horm Metab Res. 2019; 51(10): 627–633.
  13. Vos XG, Endert E, Zwinderman AH, et al. Predicting the Risk of Recurrence Before the Start of Antithyroid Drug Therapy in Patients With Graves' Hyperthyroidism. J Clin Endocrinol Metab. 2016; 101(4): 1381–1389.
  14. Kamijo K. Study on cutoff value setting for differential diagnosis between Graves' disease and painless thyroiditis using the TRAb (Elecsys TRAb) measurement via the fully automated electrochemiluminescence immunoassay system. Endocr J. 2010; 57(10): 895–902.
  15. Zuhur SS, Ozel A, Kuzu I, et al. The Diagnostic Utility of Color Doppler Ultrasonography, Tc-99m Pertechnetate Uptake, and TSH-Receptor Antibody for Differential Diagnosis of Graves' Disease and Silent Thyroiditis: A Comparative Study. Endocr Pract. 2014; 20(4): 310–319.
  16. Paunkovic J, Paunkovic N. Does autoantibody-negative Graves' disease exist? A second evaluation of the clinical diagnosis. Horm Metab Res. 2006; 38(1): 53–56.
  17. Kawai K, Tamai H, Mori T, et al. Thyroid histology of hyperthyroid Graves' disease with undetectable thyrotropin receptor antibodies. J Clin Endocrinol Metab. 1993; 77(3): 716–719.
  18. Vitti P, Rago T, Mazzeo S, et al. Thyroid blood flow evaluation by color-flow Doppler sonography distinguishes Graves' disease from Hashimoto's thyroiditis. J Endocrinol Invest. 1995; 18(11): 857–861.
  19. Werner SC. Modification of the classification of the eye changes of Graves' disease: recommendations of the Ad Hoc Committee of the American Thyroid Association. J Clin Endocrinol Metab. 1977; 44(1): 203–204.
  20. Allahabadia A, Daykin J, Holder RL, et al. Age and gender predict the outcome of treatment for Graves' hyperthyroidism. J Clin Endocrinol Metab. 2000; 85(3): 1038–1042.
  21. Quadbeck B, Roggenbuck U, Janssen OE, et al. Basedow Study Group. Impact of smoking on the course of Graves' disease after withdrawal of antithyroid drugs. Exp Clin Endocrinol Diabetes. 2006; 114(8): 406–411.
  22. Prabhakar BS, Bahn RS, Smith TJ. Current perspective on the pathogenesis of Graves' disease and ophthalmopathy. Endocr Rev. 2003; 24(6): 802–835.
  23. Bartalena L, Marcocci C, Pinchera A. Graves' ophthalmopathy: a preventable disease? Eur J Endocrinol. 2002; 146(4): 457–461.
  24. Nyirenda MJ, Taylor PN, Stoddart M, et al. Thyroid-stimulating hormone-receptor antibody and thyroid hormone concentrations in smokers vs nonsmokers with Graves disease treated with carbimazole. JAMA. 2009; 301(2): 162–164.
  25. Yanagisawa T, Sato K, Kato Y, et al. Rapid differential diagnosis of Graves' disease and painless thyroiditis using total T3/T4 ratio, TSH, and total alkaline phosphatase activity. Endocr J. 2005; 52(1): 29–36.
  26. Salvatore D, Tu H, Harney JW, et al. Type 2 iodothyronine deiodinase is highly expressed in human thyroid. J Clin Invest. 1996; 98(4): 962–968.
  27. Kawai K, Tamai H, Matsubayashi S, et al. A study of untreated Graves' patients with undetectable TSH binding inhibitor immunoglobulins and the effect of anti-thyroid drugs. Clin Endocrinol (Oxf). 1995; 43(5): 551–556.
  28. Mukuta T, Tamai H, Oshima A, et al. Immunological findings and thyroid function of untreated Graves' disease patients with undetectable TSH-binding inhibitor immunoglobulin. Clin Endocrinol (Oxf). 1994; 40(2): 215–219.
  29. Scappaticcio L, Trimboli P, Keller F, et al. Diagnostic testing for Graves' or non-Graves' hyperthyroidism: A comparison of two thyrotropin receptor antibody immunoassays with thyroid scintigraphy and ultrasonography. Clin Endocrinol (Oxf). 2020; 92(2): 169–178.
  30. Tanrikulu S, Erbil Y, Ademoglu E, et al. The predictive value of CTLA-4 and Tg polymorphisms in the recurrence of Graves' disease after antithyroid withdrawal. Endocrine. 2006; 30(3): 377–381.

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