Development of Chronic Thyroiditis During Cyclosporin A Treatment

Overview

Journal JCEM Case Rep

Specialty Endocrinology

Date 2024 Nov 21

PMID 39569043

Authors

Yuji Hataya

Takumi Nomura

Yuko Fujishima

Kanta Fujimoto

Toshio Iwakura

Naoki Matsuoka

Affiliations

Soon will be listed here.

Abstract

Cyclosporin A (CsA) is a calcineurin inhibitor used as an immunosuppressant. Although CsA effectively suppresses T cells, excessive suppression of regulatory T cells may exacerbate autoimmune diseases. Here, we report a case of chronic thyroiditis developing during CsA treatment. A 64-year-old woman, on CsA for 2 years for aplastic anemia, presented with a nodule in the right thyroid lobe, raising concern for malignant lymphoma. Right hemithyroidectomy confirmed mucosa-associated lymphoid tissue lymphoma without chronic thyroiditis in the adjacent normal tissue. Owing to the localized lesion, the patient was monitored with a reduced dose of CsA. Initial thyroid ultrasonography showed a normal left lobe; however, hypoechoic areas appeared 1-year postsurgery, followed by diffuse thyroid enlargement and further expansion of these hypoechoic areas. Postoperative fluorodeoxyglucose positron emission tomography showed progressive uptake in the left lobe, and thyroid autoantibodies, initially negative, became positive. Five years later, suspected lymphoma recurrence prompted a residual thyroidectomy, which confirmed mucosa-associated lymphoid tissue lymphoma with chronic thyroiditis. This case suggests that excessive suppression of regulatory T cells by CsA may induce chronic thyroiditis. Further studies on chronic thyroiditis in patients treated with CsA may enhance our understanding of its pathogenesis.

References

Iwasaki H . Onset of Graves' disease during long-term immunosuppressive therapy in a patient with membranous nephropathy. Endocrinol Diabetes Metab Case Rep. 2015; 2015:150046. PMC: 4557087. DOI: 10.1530/EDM-15-0046. View

Obuobie K, Al-Sabah A, Lazarus J . Subacute thyroiditis in an immunosuppressed patient. J Endocrinol Invest. 2002; 25(2):169-71. DOI: 10.1007/BF03343982. View

Tokumaru M, Ohba K, Kakudo K, Suda T, Oki Y, Goto Y . Importance of Imaging Procedures in the Evaluation of Methotrexate-Associated Lymphoproliferative Disorder of the Thyroid Gland: A Case Study. Eur Thyroid J. 2021; 10(5):434-436. PMC: 8406244. DOI: 10.1159/000507826. View

Huang Q, Liu X, Zhang Y, Huang J, Li D, Li B . Molecular feature and therapeutic perspectives of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. J Genet Genomics. 2020; 47(1):17-26. DOI: 10.1016/j.jgg.2019.11.011. View

Shin J, Park J, Lee J, Kim D, Jeong H . Development of Graves' disease during cyclosporin treatment for severe Henoch-Schönlein nephritis. Nephrol Dial Transplant. 2005; 20(9):2014-5. DOI: 10.1093/ndt/gfh959. View

Momose S, Tamaru J . Iatrogenic immunodeficiency-associated lymphoproliferative disorders of B-cell type that develop in patients receiving immunosuppressive drugs other than in the post-transplant setting. J Clin Exp Hematop. 2019; 59(2):48-55. PMC: 6661961. DOI: 10.3960/jslrt.19014. View

Walz G, Zanker B, Melton L, Suthanthiran M, Strom T . Possible association of the immunosuppressive and B cell lymphoma-promoting properties of cyclosporine. Transplantation. 1990; 49(1):191-4. DOI: 10.1097/00007890-199001000-00042. View

Vakeva L, Reitamo S, Pukkala E, Sarna S, Ranki A . Long-term follow-up of cancer risk in patients treated with short-term cyclosporine. Acta Derm Venereol. 2008; 88(2):117-20. DOI: 10.2340/00015555-0360. View

Flores C, Fouquet G, Moura I, Trovati Maciel T, Hermine O . Lessons to Learn From Low-Dose Cyclosporin-A: A New Approach for Unexpected Clinical Applications. Front Immunol. 2019; 10:588. PMC: 6447662. DOI: 10.3389/fimmu.2019.00588. View

10.

Noack M, Miossec P . Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev. 2014; 13(6):668-77. DOI: 10.1016/j.autrev.2013.12.004. View

11.

Suher M, Koc E, Ensari C, Oztugut S . Graves' disease in a renal transplant. J Nephrol. 2004; 17(5):736-8. View

12.

Xue H, Yu X, Ma L, Song S, Li Y, Zhang L . The possible role of CD4⁺CD25(high)Foxp3⁺/CD4⁺IL-17A⁺ cell imbalance in the autoimmunity of patients with Hashimoto thyroiditis. Endocrine. 2015; 50(3):665-73. DOI: 10.1007/s12020-015-0569-y. View

13.

Bednarczuk T, Makowska U, Nauman J . Development of Graves' disease in a patient under immunosuppressive therapy after liver transplantation. J Endocrinol Invest. 2003; 26(3):257-60. DOI: 10.1007/BF03345166. View

14.

Peslak S, Olson T, Babushok D . Diagnosis and Treatment of Aplastic Anemia. Curr Treat Options Oncol. 2017; 18(12):70. PMC: 5804354. DOI: 10.1007/s11864-017-0511-z. View

15.

Zwart E, Yuksel E, Pannekoek A, de Vries R, Mebius R, Kazemier G . De Novo Carcinoma after Solid Organ Transplantation to Give Insight into Carcinogenesis in General-A Systematic Review and Meta-Analysis. Cancers (Basel). 2021; 13(5). PMC: 7961956. DOI: 10.3390/cancers13051122. View

16.

Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan A, Stroud J . FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell. 2006; 126(2):375-87. DOI: 10.1016/j.cell.2006.05.042. View

17.

Cattoni A, Molinari S, Riva B, Di Marco S, Adavastro M, Faraguna M . Thyroid function disorders and secondary cancer following haematopoietic stem cell transplantation in pediatrics: State of the art and practical recommendations for a risk-based follow-up. Front Endocrinol (Lausanne). 2023; 13:1064146. PMC: 9811586. DOI: 10.3389/fendo.2022.1064146. View

18.

Khovidhunkit W, GREENSPAN F, Jaume J . Development of overt autoimmune hyperthyroidism in a patient therapeutically immunosuppressed after liver transplantation. Thyroid. 2000; 10(9):829-32. DOI: 10.1089/thy.2000.10.829. View

19.

Weetman A . An update on the pathogenesis of Hashimoto's thyroiditis. J Endocrinol Invest. 2020; 44(5):883-890. PMC: 8049926. DOI: 10.1007/s40618-020-01477-1. View

20.

Hofle G, Moncayo R, Baldissera I, Pfister R, Finkenstedt G . Endocrine ophthalmopathy in a patient under continuous immunosuppressive therapy after cardiac transplantation. Thyroid. 1995; 5(6):477-80. DOI: 10.1089/thy.1995.5.477. View