Levels of Antithyroid Antiperoxidase and Antithyroglobulin Antibodies in Patients with Graves Hyperthyroidism – Predictors of Initial and Sustained Remission and Consecutive Hypothyroidism

Main Article Content

Natasha Stojkovska
Nevena Manevska
Tanja Makazlieva
Sinisha Stojanoski


BACKGROUND: Initial and sustained remission is the principal objective in patients with Graves hyperthyroidism (GH) treated with antithyroid drugs (ATD).

AIMS: Our study aimed to investigate the predictive value of antithyroid antiperoxidase (aTPO) and antithyroglobulin (aTg) levels on initial and sustained remission or consecutive hypothyroidism in subjects with GH treated with ATD.

METHODS: Randomized, prospective, and longitudinal study during period 2013–2018 was performed. Eighty GH patients (thyrotropin [TSH] <0.01 mIU/L, free thyroxine [FT4] >30 pmol/L, triiodothyronine [FT3] >8 pmol/L), 59 females (73.75%), and 21 males (26.25%), aged 51 ± 12 years were included in the study. Subjects were divided into four subgroups (each with 20 patients) according to aTPO and aTg levels: Group I – no antibodies; Group II – (<500 IU/mL), Group III – (500–1000 IU/mL), and Group IV – (>1000 IU/mL). All subjects underwent 24 months of propylthiouracil treatment with follow-up of 24 months after remission (TSH >0.4 mIU/L, FT4 11–25 pmol/L, FT3 2.8–6.5 pmol/L). Blood samples were analyzed every 4 months.

RESULTS: In Group I, 11 (55%) of the patients attained remission; during follow-up, 5 (45%) of them had disease relapse. In Group II, 12 (60%) attained remission and 5 (42%) had relapse. In Group III, 15 (75%) attained remission, 2 (13%) had disease relapse, and 4 (26%) developed hypothyroidism. In Group IV, 18 (90%) attained remission, 1 (5%) had disease relapse, and 9 (50%) developed hypothyroidism. Patients with values below 500 IU/mL attained remission in 60%, similar as the group without antibodies in 55% (p < 0.3). Patients in Group III and IV had significantly higher remission rates compared to Group I and II (p < 0.001). Baseline values of aTPO and aTg >1000 IU/mL were significant predictors of consecutive hypothyroidism (p < 0.05).

CONCLUSION: Baseline aTPO and aTg values above 500 IU/mL were significantly prognostic for attaining and  sustaining  remission  in  GH  and  values  above  1000  IU/mL  were  significant  predictors  of  consecutive hypothyroidism.


Download data is not yet available.

Plum Analytics

Article Details

How to Cite
Stojkovska N, Manevska N, Makazlieva T, Stojanoski S. Levels of Antithyroid Antiperoxidase and Antithyroglobulin Antibodies in Patients with Graves Hyperthyroidism – Predictors of Initial and Sustained Remission and Consecutive Hypothyroidism. SEE J Immunol [Internet]. 2023 Aug. 25 [cited 2024 Jun. 16];6(1):83-6. Available from: https://seejim.eu/index.php/seejim/article/view/6052
Clinical Immunology


Argas-Uricoechea H, Bonelo-Perdomo A, Sierra-Torres CH, Meza-Cabrera I. Autoimmune thyroid disease (flajani-parry-graves-von basedow disease): Etiopathogenesis, clinical manifestations and diagnosis. In: Imam S, Ahmad S, editors. Thyroid Disorders. Cham: Springer; 2016.

Yanachkova V, Kamenov Z. The relationship between thyroid dysfunction during pregnancy and gestational diabetes mellitus. Endokrynol Pol. 2021;72(3):226-31. https://doi.org/10.5603/EP.a2021.0016 PMid:33619713

De Groot LJ, Larsen PR, Hennemann G. The Thyroid and its Diseases. 6th ed. United Kingdom: Churchill Livingstone; 1995

Weetman A. Autoimmune thyroid disease. Endocrine. 2020;68(2):258-60. https://doi.org/10.1007/s12020-020-02188-6 PMid:320523689.

Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, Pearce SH. 2018 European thyroid association guideline for the management of graves’ hyperthyroidism. Eur Thyroid J. 2018;7(4):167-86. http://doi.org/10.1159/000490384 PMid:302837357.

McGrogan A, Seaman HE, Wright JW, de Vries CS. The incidence of autoimmune thyroid disease: A systematic review of the literature. Clin Endocrinol (Oxf). 2008;69(5):687-96. https://doi.org/10.1111/j.1365-2265.2008.03338.x PMid:18673466

Walsh JP, Bremner AP, Feddema P, Leedman PJ, Brown SJ, O’Leary P. Thyrotropin and thyroid antibodies as predictors of hypothyroidism: A 13-year, longitudinal study of a community- based cohort using current immunoassay techniques. J Clin Endocrinol Metab. 2010;95(3):1095-104. http://doi.org/10.1210/jc.2009-1977 PMid:20097710

Wahab F, Kearney E, Joseph S. The presence of thyroid peroxidase antibodies in Graves’ disease is predictive of disease duration and relapse rates. Endocr Abstr. 2013;31:P367. https://doi.org/10.1530/endoabs.31.P367

Bartalena L, Piantanida E, Gallo D, Ippolito S, Tanda ML. Management of Graves’ hyperthyroidism: Present and future. Expert Rev Endocrinol Metab. 2022;17(2):153-66. http://doi.org/10.1080/17446651.2022.2052044 PMid:35287535

Vargas-Uricoechea H. Molecular mechanisms in autoimmune thyroid disease. Cells. 2023;12(6):918. http://doi.org/10.3390/cells12060918 PMid:36980259

Bossowski A, Stasiak-Barmuta A, Urban M. Relationship between CTLA-4 and CD28 molecule expression on T lymphocytes and stimulating and blocking autoantibodies to the TSH-receptor in children with Graves’ disease. Horm Res. 2005;64(4):189-97. https://doi.org/10.1159/000088875 PMid:16220002

De Carvalho G, Perez C, Ward L. The clinical use of thyroid function tests. Arq Bras Endocrinol Metabol 2013;57(3):193-

https://doi.org/10.1590/S0004-27302013000300005 PMid:23681265

Fröhlich E, Wahl R. Thyroid autoimmunity: Role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front Immunol. 2017;8:521. http://doi.org/10.3389/fimmu.2017.00521 PMid:28536577

Kaczur V, Vereb G, Molnár I, Krajczár G, Kiss E, Farid NR, et al. Effect of anti-thyroid peroxidase (TPO) antibodies on TPO activity measured by chemiluminescence assay. Clin Chem 1997;43(8 Pt 1):1392-6. PMid:9267319

Xie LD, Gao Y, Li MR, Lu GZ, Guo XH. Distribution of immunoglobulin G subclasses of anti-thyroid peroxidase antibody in sera from patients with Hashimoto’s thyroiditis with different thyroid functional status. Clin Exp Immunol. 2008;154(2):172-6. https://doi.org/10.1111/j.1365-2249.2008.03756.x PMid:18778360

Caturegli P, Kuppers RC, Mariotti S, Burek CL, Pinchera A, Ladenson PW, et al. IgG subclass distribution of thyroglobulin antibodies in patients with thyroid disease. Clin Exp Immunol 1994;98(3):464-9. https://doi.org/10.1111/j.1365-2249.1994.tb05514.x PMid:7994910

Siriwardhane T, Krishna K, Ranganathan V, Jayaraman V, Wang T, Bei K, et al. Significance of anti-TPO as an early predictive marker in thyroid disease. Autoimmune Dis. 2019;2019:1684074. https://doi.org/10.1155/2019/1684074 PMid:31467701

Azizi F, Amouzegar A, Tohidi M, Hedayati M, Khalili D, Cheraghi L, et al. Increased remission rates after long-term methimazole therapy in patients with Graves’ disease: Results of a randomized clinical trial. Thyroid. 2019;29(9):1192-200. https://doi.org/10.1089/thy.2019.0180 PMid:31310160

Alhubaish ES, Alibrahim NT, Mansour AA. The Clinical Implications of anti-thyroid peroxidase antibodies in Graves’ disease in basrah. Cureus. 2023;15(3):e36778. https://doi.org/10.7759/cureus.36778 PMid:37123800