Yonsei Med J.  2016 May;57(3):795-798. 10.3349/ymj.2016.57.3.795.

Graves' Patient with Thymic Expression of Thyrotropin Receptors and Dynamic Changes in Thymic Hyperplasia Proportional to Graves' Disease Activity

• Song YS
• Won JK
• Kim MJ
• Lee JH
• Kim DW
• Chung JK
• Park DJ
• Park YJ

• KMID: 2374104
• DOI: http://doi.org/10.3349/ymj.2016.57.3.795

Abstract

Thymic hyperplasia is frequently observed in Graves' disease. However, detectable massive enlargement of the thymus is rare, and the mechanism of its formation has remained elusive. This case showed dynamic changes in thymic hyperplasia on serial computed tomography images consistent with changes in serum thyrotropin receptor (TSH-R) antibodies and thyroid hormone levels. Furthermore, the patient's thymic tissues underwent immunohistochemical staining for TSH-R, which demonstrated the presence of thymic TSH-R. The correlation between serum TSH-R antibody levels and thymic hyperplasia sizes and the presence of TSH-R in her thymus suggest that TSH-R antibodies could have a pathogenic role in thymic hyperplasia.

Keyword

Thymus hyperplasia; graves disease; receptors thyrotropin; immunoglobulins, thyroid-stimulating

MeSH Terms

Adult
Female
Graves Disease/*complications/surgery/therapy
Humans
Male
Receptors, Thyrotropin/blood
Thymus Gland/diagnostic imaging
Thymus Hyperplasia/*diagnostic imaging/etiology/immunology
Thyroid Hormones
Thyroidectomy
Thyrotropin/blood
Tomography, X-Ray Computed
Young Adult
Receptors, Thyrotropin
Thyroid Hormones
Thyrotropin

Figure

• 

  Fig. 1 Serial chest computed tomography images showing dynamic changes in thymic hyperplasia. (A) Image obtained at initial visit and at (B) 33 months, (C) 63 months, and (D) 73 months after the initial visit.

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  Fig. 2 Immunohistochemistry of thyrotropin receptors (TSH-R) in the patient's thyroid and thymic tissue and in negative control thymic tissue. (A) Immunohistochemistry of the patient's thyroid gland (200× and 400×). Follicular epithelial cells were weakly stained by antibodies for TSH-R. (B) Immunohistochemistry of the patient's thymus (100×). TSH-R was mainly expressed in the thymic medulla. (C) Immunohistochemistry of the medulla of the thymus (200× and 400×). TSH-R expression was observed in Hassall's corpuscles and epithelial reticular cells rather than in lymphocytes. (D) Immunohistochemistry of non-neoplastic thymic tissue from a subject without Graves' disease (200×). TSH-R expression was not observed in the entire thymus.

Reference

1. Michie W, Gunn A. The thyroid, the thymus and autoimmunity. Br J Clin Pract. 1966; 20:9–13.

2. Yamanaka K, Nakayama H, Watanabe K, Kameda Y. Anterior mediastinal mass in a patient with Graves' disease. Ann Thorac Surg. 2006; 81:1904–1906.

3. Popoveniuc G, Sharma M, Devdhar M, Wexler JA, Carroll NM, Wartofsky L, et al. Graves' disease and thymic hyperplasia: the relationship of thymic volume to thyroid function. Thyroid. 2010; 20:1015–1018.

4. Suh H, Rosen JE, Doherty GM, Saunders BD, McAneny D. Graves' disease and thymic hyperplasia. Surgery. 2013; 154:1473–1477.

5. Nakamura T, Murakami M, Horiguchi H, Nagasaka S, Ishibashi S, Mori M, et al. A case of thymic enlargement in hyperthyroidism in a young woman. Thyroid. 2004; 14:307–310.

6. Murakami M, Hosoi Y, Negishi T, Kamiya Y, Miyashita K, Yamada M, et al. Thymic hyperplasia in patients with Graves' disease. Identification of thyrotropin receptors in human thymus. J Clin Invest. 1996; 98:2228–2234.

7. Hassman R, Weetman AP, Gunn C, Stringer BM, Wynford-Thomas D, Hall R, et al. The effects of hyperthyroidism on experimental autoimmune thyroiditis in the rat. Endocrinology. 1985; 116:1253–1258.

8. Fabris N. Immunodepression in thyroid-deprived animals. Clin Exp Immunol. 1973; 15:601–611.

9. Fabris N, Mocchegiani E, Mariotti S, Pacini F, Pinchera A. Thyroid function modulates thymic endocrine activity. J Clin Endocrinol Metab. 1986; 62:474–478.

10. Bergman TA, Mariash CN, Oppenheimer JH. Anterior mediastinal mass in a patient with Graves' disease. J Clin Endocrinol Metab. 1982; 55:587–588.