Overlap syndrome in autoimmune thyroid diseases: pathogenesis, diagnosis, and therapeutic approaches

Grygorii Gendeleka

doi:10.35434/rcmhnaaa.2025.184.3038

Autores/as

Grygorii Gendeleka Odesa National Medical University

DOI:

https://doi.org/10.35434/rcmhnaaa.2025.184.3038

Palabras clave:

Enfermedades de la Tiroides, síndrome de superposición, hipertiroidismo, hipotiroidismo, endocrinología

Resumen

El objetivo del estudio es resumir los datos actuales sobre los mecanismos patogénicos, las manifestaciones clínicas y los criterios diagnósticos del síndrome de solapamiento en las enfermedades tiroideas autoinmunes e identificar posibles biomarcadores y orientaciones para mejorar las estrategias terapéuticas a fin de aumentar la eficacia del tratamiento y predecir el curso de esta patología. En este sentido, se realizó una búsqueda de publicaciones en las bases de datos PubMed, MEDLINE y Web of Science para el periodo 1980-2025. Se describieron casos clínicos en los que la transformación se produjo bajo la influencia de la terapia y de forma espontánea. Se establece que los anticuerpos (TPOAb, TgAb, TSHrAb), los niveles de hormona tiroidea y los métodos instrumentales desempeñan un papel clave en el diagnóstico. Se destacan los mecanismos moleculares, en particular los cambios epigenéticos (metilación del ADN), los perfiles de microARN, el papel de los exosomas y el mimetismo antigénico de agentes infecciosos, incluido el SARS-CoV-2. Se demuestra que diversos mecanismos pueden causar predominio y alternancia entre procesos autoinmunes.

Descargas

Los datos de descargas todavía no están disponibles.

Métricas

Cargando métricas ...

Biografía del autor/a

Grygorii Gendeleka, Odesa National Medical University

D.Sc. in Medicine, Professor

Citas

Garcia-Mayor RV. Alternating Graves’ hyperthyroidism and Hashimoto’s hypothyroidism for more than 20 years: a case report. J Endocrinol Thyroid Res. 2023;7(3):555714. doi:10.19080/JETR.2023.07.555714

Hendeleka H. An autoimmune overlap syndrome in diseases of the thyroid gland – Terra incognita of thyroidology. Int J Endocrinol (Ukraine). 2016;2(74):140-51. doi:10.22141/2224-0721.2.74.2016.70960

Jury EC, D’Cruz D, Morrow WJ. Autoantibodies and overlap syndromes in autoimmune rheumatic disease. J Clin Pathol. 2001;54(5):340-7. doi:10.1136/jcp.54.5.340

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

Tywanek E, Michalak A, Świrska J, Zwolak A. Autoimmunity, new potential biomarkers and the thyroid gland – the perspective of Hashimoto’s thyroiditis and its treatment. Int J Mol Sci. 2024;25(9):4703. doi:10.3390/ijms25094703

Arbex A, Magalhaes I, Montenegro A, Arbex M, Arbex G, Bussuan R. Hashimoto’s thyroiditis or Graves’ disease? A case of thyroid autoimmune disease with oscillating thyroid function. Joint Congress of the European Society for Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE) 2025: Connecting Endocrinology Across the Life Course. 2025;110:EP1508. doi:10.1530/endoabs.110.EP1508

Vassallo A, Ferrari F, di Filippo L, Giustina A, Loli P. Transition from Hashimoto thyroiditis to Graves’ disease: an unpredictable change? Endocrine. 2024;84(2):541-8. doi:10.1007/s12020-023-03634-x

Kahaly GJ. Management of Graves’ thyroidal and extrathyroidal disease: an update. J Clin Endocrinol Metab. 2020;105(12):3704-20. doi:10.1210/clinem/dgaa646

Hu X, Chen Y, Shen Y, Tian R, Sheng Y, Que H. Global prevalence and epidemiological trends of Hashimoto's thyroiditis in adults: a systematic review and meta-analysis. Front Public Health. 2022;10:1020709. doi:10.3389/fpubh.2022.1020709

Jadhav R, Alberawi M, Gupta K. Graves’ disease: a rare fate of Hashimoto’s thyroiditis. World J Nucl Med. 2020;20(1):102-4. doi:10.4103/wjnm.WJNM_34_20

Daramjav N, Takagi J, Iwayama H, Uchino K, Inukai D, Otake K, et al. Autoimmune thyroiditis shifting from Hashimoto’s thyroiditis to Graves’ disease. Medicina (Kaunas). 2023;59(4):757. doi:10.3390/medicina59040757

Gonzalez-Aguilera B, Betea D, Lutteri L, Cavalier E, Geenen V, Beckers A, et al. Conversion to Graves’ disease from Hashimoto thyroiditis: a study of 24 patients. Arch Endocrinol Metab. 2018;62(6):609-14. doi:10.20945/2359-3997000000086

Liu Y, Liu X, Wu N. A review of testing for distinguishing Hashimoto’s thyroiditis in the hyperthyroid stage and Graves’ disease. Int J Gen Med. 2023;16:2355-63. doi:10.2147/IJGM.S410640

Saravanan P, Dayan CM. Thyroid autoantibodies. Endocrinol Metab Clin North Am. 2001;30(2):315-37. doi:10.1016/S0889-8529(05)70189-4

Takasu N, Matsushita M. Changes of TSH-stimulation blocking antibody (TSBAb) and thyroid stimulating antibody (TSAb) over 10 years in 34 TSBAb-positive patients with hypothyroidism and in 98 TSAb-positive Graves’ patients with hyperthyroidism: Reevaluation of TSBAb and TSAb in TSH-receptor-antibody (TRAb)-positive patients. J Thyroid Res. 2012;2012:182176. doi:10.1155/2012/182176

McLachlan SM, Aliesky HA, Rapoport B. Nanoparticles bearing TSH receptor protein and a tolerogenic molecule do not induce immune tolerance but exacerbate thyroid autoimmunity in hTSHR/NOD.H2h4 mice. J Immunol. 2019;202(9):2570-7. doi:10.4049/jimmunol.1900038

Padmanaban P, Jain R. Autoimmune switch from hyperthyroidism to hypothyroidism in Graves’ disease. BMJ Case Rep. 2020;13(11):e236465. doi:10.1136/bcr-2020-236465

Lee YL. Oscillation between hyperthyroidism and hypothyroidism in an adolescent female with Graves’ disease. J ASEAN Fed Endocr Soc. 2025;40(1):117-20. doi:10.15605/jafes.040.01.07

Wong M, Inder WJ. Alternating hyperthyroidism and hypothyroidism in Graves’ disease. Clin Case Rep. 2018;6(9):1684-8. doi:10.1002/ccr3.1700

Shkala LV, Shkala OV. Analysis of the causes and clinical course of thyroid diseases in the presence of autoimmune overlap syndrome. Clin Endocrinol Endocr Surg. 2025;1:85-92. doi:10.30978/CEES-2025-1-85

Martins LC, Coutinho AR, Jerónimo M, Caetano JS, Cardoso R, Dinis I, et al. Autoimmune alternating hyper- and hypo-thyroidism: a rare condition in paediatrics. Endocrinol Diabetes Metab Case Rep. 2016;1:1-5. doi:10.1530/EDM-15-0131

Fan W, Tandon P, Krishnamurthy M. Oscillating hypothyroidism and hyperthyroidism – a case-based review. J Community Hosp Intern Med Perspect. 2014;4(5). doi:10.3402/jchimp.v4.25734

Samyukta R, Samykta R, Yusra J. The flip-flopping thyroid disease: a case of transformation of Hashimoto thyroiditis to Graves’ disease. Endocr Pract. 2024;30(5):S148. doi:10.1016/j.eprac.2024.03.059

Furqan S, Haque NU, Islam N. Conversion of autoimmune hypothyroidism to hyperthyroidism. BMC Res Notes. 2014;7:489. doi:10.1186/1756-0500-7-489

Skov J, Calissendorff J, Eriksson D, Magnusson P, Kämpe O, Bensing S, et al. Limited genetic overlap between overt Hashimoto’s thyroiditis and Graves’ disease in twins: a population-based study. J Clin Endocrinol Metab. 2021;106(4):1101-10. doi:10.1210/clinem/dgaa956

Lafontaine N, Wilson SG, Walsh JP. DNA methylation in autoimmune thyroid disease. J Clin Endocrinol Metab. 2023;108(3):604-13. doi:10.1210/clinem/dgac664

Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484-92. doi:10.1038/nrg3230

Guo Q, Wu D, Yu H, Bao J, Peng S, Shan Z, et al. Alterations of global DNA methylation and DNA methyltransferase expression in T and B lymphocytes from patients with newly diagnosed autoimmune thyroid diseases after treatment: a follow-up study. Thyroid. 2018;28(3):377-85. doi:10.1089/thy.2017.0301

Zhou Z, Liu J, Chen Y, Ren B, Wan S, Chen Y, et al. Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis. Front Endocrinol. 2023;14:1259903. doi:10.3389/fendo.2023.1259903

Zheng L, Zhuang C, Wang X, Ming L. Serum miR-146a, miR-155, and miR-210 as potential markers of Graves’ disease. J Clin Lab Anal. 2018;32(2):e22266. doi:10.1002/jcla.22266

Heegaard NHH, Carlsen AL, Skovgaard K, Heegaard PMH. Circulating extracellular microRNA in systemic autoimmunity. In: Igaz P, editor. Circulating microRNAs in disease diagnostics and their potential biological relevance. Experientia Supplementum. Basel: Springer; 2015. p. 171-95. doi:10.1007/978-3-0348-0955-9_8

Bekerman E, Jeon D, Ardolino M, Coscoy L. A role for host activation-induced cytidine deaminase in innate immune defence against KSHV. PLoS Pathog. 2013;9(11):e1003748. doi:10.1371/journal.ppat.1003748

Jia X, Zhai T, Zhang JA. Circulating exosome involves in the pathogenesis of autoimmune thyroid diseases through immunomodulatory proteins. Front Immunol. 2021;12:730089. doi:10.3389/fimmu.2021.730089

Marshall MR, Pattu V, Halimani M, Maier-Peuschel M, Müller ML, Becherer U, et al. VAMP8-dependent fusion of recycling endosomes with the plasma membrane facilitates T lymphocyte cytotoxicity. J Cell Biol. 2015;210(1):135-51. doi:10.1083/jcb.201411093

Figura N, Di Cairano G, Moretti E, Iacoponi F, Santucci A, Bernardini G, et al. Helicobacter pylori infection and autoimmune thyroid diseases: The role of virulent strains. Antibiotics. 2019;9(1):12. doi:10.3390/antibiotics9010012

Kravchenko V, Rakov O. A rare case of transformation of autoimmune thyroiditis into Graves’ disease after COVID-19 disease. J Clin Med Images. 2021;5(10):1-3.

Panesar A, Gharanei P, Khovanova N, Young L, Grammatopoulos D. Thyroid function during COVID-19 and post-COVID complications in adults: a systematic review. Front Endocrinol. 2025;15:1477389. doi:10.3389/fendo.2024.1477389