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Journal of Endocrinological Investigation

, Volume 37, Issue 12, pp 1175–1179 | Cite as

Thymic hyperplasia in patients with Graves’ disease

  • M. Dalla Costa
  • F. A. Mangano
  • C. Betterle
Short Review

Abstract

Background

Graves’ disease (GD) is commonly associated with other autoimmune conditions, and there is also a rare but well documented association between GD and thymic hyperplasia (TH). It is hard to say the real frequency of this latter association because most cases remain asymptomatic and are consequently not thoroughly investigated.

Materials and Methods

We reviewed the literature on GD-related thymus enlargement and found 107 cases published to date. Thymic cancer was only documented in four patients, while the majority of cases were diagnosed as TH. The causative mechanisms behind TH associated with GD have yet to be fully elucidated. Several studies support the hypothesis of a TSH receptor antibody (TRAb) mediating thymic enlargement.

Results

We report on a female GD patient with an incidentally discovered anterior mediastinal mass. Our case is not consistent with the hypothesis of a TRAb-mediated mechanism because the thymus reached its largest volume at the onset of GD and shrank during remission of GD under medical treatment, despite persistently positive TRAb levels.

Conclusion

We support the hypothesis that two different pathogenic mechanisms might be responsible for thymus enlargement: thymic cortical tissue expansion seems to be due to a hyperthyroid state, while lymphoid hyperplasia appears to correlate with immune abnormalities underlying GD.

Keywords

Graves’ disease Thymic hyperplasia TSH receptor antibody (TRAb) 

Notes

Conflict of interest

The authors do not have any conflicts of interest.

References

  1. 1.
    Brent GA (2008) Clinical practice. Graves’ disease. N Engl J Med 358:2594–2605PubMedCrossRefGoogle Scholar
  2. 2.
    Wiebolt J, Achterbergh R, Den Boer A, Van Der Leij S, Marsch E, Suelmann B, De Vries R, Van Haeften TW (2011) Clustering of additional autoimmunity behaves differently in Hashimoto’s patients compared with Graves’ patients. Eur J Endocrinol 164:789–794PubMedCrossRefGoogle Scholar
  3. 3.
    Halsted WS (1914) Significance of the thymus gland in Graves’ disease. Bull Johns Hopkins Hosp 25:223–224Google Scholar
  4. 4.
    Gunn A, Michie W, Irvine WJ (1964) The thymus in thyroid disease. Lancet 2:776–778PubMedCrossRefGoogle Scholar
  5. 5.
    Murakami M, Hosoi Y, Negishi T, Kamiya Y, Miyashita K, Yamada M, Iriuchijima T, Yokoo H, Yoshida I, Tsushima Y, Mori M (1996) Thymic hyperplasia in patients with Graves’ disease. Identification of thyrotropin receptors in human thymus. J Clin Invest 98:2228–2234PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Nakamura S (2012) Thymic enlargement in two cases of Graves’ disease. Internal Med 51:673–674CrossRefGoogle Scholar
  7. 7.
    Michie W, Gunn A (1966) The thyroid, the thymus and autoimmunity. Br J Clinic Pract 20:9–13Google Scholar
  8. 8.
    Michie W, Beck JS, Mahaffy RG, Honein EF, Fowler GB (1967) Quantitative radiological and histological studies of the thymus in thyroid disease. Lancet 1:691–695PubMedCrossRefGoogle Scholar
  9. 9.
    Deforges-Bullet V, Petit-Aubert G, Collet-Gaudillat C, Cerceau R, Fraleu-Louer B, Meckenstock R, Greder A, Cordoliani Y, Beressi JP (2011) Thymic hyperplasia and Graves’ disease: a non-fortuitous association. Case report and review of literature. Annales d’Endocrinologie 72:304–309CrossRefGoogle Scholar
  10. 10.
    Kubicky RA, Faerber EN, Chadarevian JP, Wu S, Rezvani I, De Luca F (2010) An adolescent with a mediastinal mass, diagnosed with Graves’ disease and thymic hyperplasia. Pediatrics 125:433–437CrossRefGoogle Scholar
  11. 11.
    Takami K, Hideyasu O, Higashiyama M, Maeda J, Okami J, Oda k, Tsujinaka T, Kodama K (2009) A case report of large thymic hyperplasia associated with hyperthyroidism. Ann Thorac Cardiovasc Surg 15:404–407PubMedGoogle Scholar
  12. 12.
    Suh H, Rosen JE, Doherty GM, Sauders BD, McAneny D (2013) Graves’ disease and thymic hyperplasia. Surgery 154:1473–1477Google Scholar
  13. 13.
    Danilovic DL, Martin RM, Caruso P, Marui S (2011) Thymic hyperplasia in Graves’ disease. Clinics 66:2177–2178PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Kawano A, Kohno H (2011) Thymic hyperplasia associated with Graves’ disease in a 10-year-old boy. Clin Pediatr Endocrinol 20:61–64PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Nguyen HD, Galitz MS, Clark DD (2011) Visual vignette. What is the diagnosis? Thymic hyperplasia associated with Graves disease. Endocr Pract 17:833PubMedCrossRefGoogle Scholar
  16. 16.
    Hamzaoui A, Kilii R, Salem R, Kochtali I, Golli M, Mahjoub S (2012) Thymic hyperplasia in a patient with Graves’ disease. Int Arch Med 9:5–6Google Scholar
  17. 17.
    Kotwal N, Singh Y, Menon A, Behera V (2013) Thymic hyperplasia in Graves’ disease. Indian J Andorinol Metab 17:521–523CrossRefGoogle Scholar
  18. 18.
    Levy Y, Afek A, Sherer Y, Bar-Dayan Y, Shibi R, Kopolovic J, Shoenfeld Y (1998) Malignant thymoma associated with autoimmune diseases: a retrospective study and review of the literature. Semin Arthritis Rheum 28:73–79PubMedCrossRefGoogle Scholar
  19. 19.
    Lee BW, Ihm SH, Shin HS, Yoo HJ (2008) Malignant thymoma associated with myasthenia gravis, Graves’ disease, and SIADH. Intern Med 47:1009–1012PubMedCrossRefGoogle Scholar
  20. 20.
    Boyd JD, Juskeviucius R (2012) Mediastinal neoplasm in patients with Graves’ disease: a possible link between sustained hyperthyroidism and thymic neoplasia? Thyr Res 5:5PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Nakamura T, Murakami M, Horiguchi H, Nagasaka S, Ishibashi S, Mori M, Ishikawa SE (2004) A case of thymic enlargement in hyperthyroidism in a young woman. Thyroid 14:307–310PubMedCrossRefGoogle Scholar
  22. 22.
    D’Souza S, Patel P, Hageman JR, Deplewski D (2014) An adolescent with Graves’ disease and thymic hyperplasia. Pediatr Ann 43:65–68CrossRefGoogle Scholar
  23. 23.
    Baron RL, Lee JK, Sagel SS, Peterson RR (1982) Computed tomography of the normal thymus. Radiology 142:121–125PubMedCrossRefGoogle Scholar
  24. 24.
    Araki T, Sholl LM, Gerbaudo VH, Hatabu H, Nishino M (2014) Imaging characteristics of pathologically proven thymic hyperplasia: identifying features that can differentiate true from lymphoid hyperplasia. Am J Roentgenol 202:471–478CrossRefGoogle Scholar
  25. 25.
    Takahashi K, Inaoka T, Murakami N, Hirota H, Iwata K, Nagasawa K, Yamada T, Mineta M, Aburano T (2003) Characterization of the normal and hyperplastic thymus on chemical-shift MR imaging. Am J Roentgenol 180:1265–1269CrossRefGoogle Scholar
  26. 26.
    Inaoka T, Takahashi K, Mineta M, Yamada T, Shuke N, Okizaki A, Nagasawa K, Sugimori H, Aburano T (2007) Thymic hyperplasia and thymus gland tumors: differentiation with chemical shift MR imaging. Radiology 43:869–876CrossRefGoogle Scholar
  27. 27.
    McIver B, Morris JC (1998) The pathogenesis of Graves’ disease. Endocrol Metab Clin North Am 27:73–89CrossRefGoogle Scholar
  28. 28.
    Van Herle AJ, Chopra IJ (1971) Thymic hyperplasia in Graves’ disease. J Clin Endocrinol Metab 32:140–146PubMedCrossRefGoogle Scholar
  29. 29.
    Hassman R, Weetman AP, Gunn C, Stringer BM, Wynford-Thomas D, Hall R, McGregor A (1985) The effects of hyperthyroidism on experimental autoimmune thyroiditis in the rat. Endocrinology 116:1253–1258PubMedCrossRefGoogle Scholar
  30. 30.
    Fabris N (1973) Immunodepression in thyroid-deprived animals. Clin Exp Immunol 15:601–611PubMedCentralPubMedGoogle Scholar
  31. 31.
    Iitaka M, Miura S, Yamanaka K, Kawasaki S, Kitahama S, Kawakami S, Oosuga I, Wada S, Katayama S (1998) Increased serum vascular endothelial growth factor levels and intrathyroidal vascular area in patients with Graves’ disease and Hashimoto’s thyroiditis. J Clin Endocrinol Metab 83:3908–3912PubMedGoogle Scholar
  32. 32.
    Figueroa-Vega N, Sanz-Cameno P, Moreno. Otero R, Sanchez-Madrid F, Gonzales-Amaro R, Marazuela M (2009) Serum levels of angiogenetic molecules in autoimmune thyroid diseases and their correlation with laboratory and clinical features. J Clin Endocrinol Metab 94:1145–1153PubMedCrossRefGoogle Scholar
  33. 33.
    Murakami M, Hosoi Y, Araki O, Morimura T, Imamura M, Ogiwara T, Mizuma H, Mori M (2001) Expression of thyreotropin receptors in rat thymus. Life Sci 68:2781–2787PubMedCrossRefGoogle Scholar
  34. 34.
    Wortsman J, McConnachies P, Baker J, Burman K (1988) Immunoglobulins that cause thymocyte proliferation from a patient with Graves’ disease and an enlarged thymus. Am J Med 85:117–121PubMedCrossRefGoogle Scholar
  35. 35.
    Popoveniuc G, Sharma M, Devdhar M, Wexler JA, Carroll NM, Wartofsky L, Burman KD (2010) Graves’ disease and thymic hyperplasia: the relationship of thymic volume to thyroid function. Thyroid 9:1015–1018CrossRefGoogle Scholar
  36. 36.
    Fabris N, Mocchegani E, Mariotti S, Pacini F, Pinchera A (1986) Thyroid function modulates thymic endocrine avtivity. J Clin Endocrinol Metab 62:474–478PubMedCrossRefGoogle Scholar
  37. 37.
    Simpson JG, Gray ES, Michies W, Becks JS (1975) The influence of preoperative drug treatment on the extent of hyperplasia of the thymus in primary thyrotoxicosis. Clin Exp Immunol 22:249–255PubMedCentralPubMedGoogle Scholar
  38. 38.
    Volpé R (1979) Auto-immunity in the Endocrine System. Springer, BerlinGoogle Scholar
  39. 39.
    Savino W, Dardenne M (2000) Neuroendocrine control of thymus physiology. Endocr Rev 21:412–413PubMedGoogle Scholar
  40. 40.
    Weetman AP, McGregor AM, Hall R (1984) Evidence for an effect of antithyroid drugs on the natural history of Graves’ disease. Clin Endocrinol 21:163–172CrossRefGoogle Scholar
  41. 41.
    Cooper DS (2005) Antithyroid drugs. N Engl J Med 352:905–917PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2014

Authors and Affiliations

  1. 1.Endocrine Unit, Department of MedicineUniversity of Padova School of MedicinePadovaItaly
  2. 2.Radiology UnitAzienda Ospedaliera-UniversitariaPadovaItaly

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