Thymic hyperplasia in a patient with Grave's disease
© Hamzaoui et al; licensee BioMed Central Ltd. 2012
Received: 16 December 2011
Accepted: 9 February 2012
Published: 9 February 2012
Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia.
KeywordsGrave's disease thymic hyperplasia Hyperthyroidism
Thymic hyperplasia (TH) is a common feature in Graves' disease (GD) and the relationship between GD and thymic changes is discussed [1, 2]. However, in most cases, thymic enlargement is minimal. Recognizing the association between TH and GD, and existence of the benign course after treatment of the hyperthyroidism may be useful for avoiding unnecessary surgical procedure.
We report a 46-year-old 40 × 30 × 50 mm, woman with GD and hyperthyroidism. She had an anterior mediastinal mass that was diagnosed as TH and disappeared after treatment of the hyperthyroid state.
A 46 year-old-woman was referred to our hospital, because of weakness and hemopthaesia. Medical history, social history, and family history were non contributory, and the patient took no medications. Her physical examination was normal. The thyroid gland did not appear prominent. Results of routine laboratory studies were all normal. Thyroid function tests demonstrated as follows: free T4 to be 5.8 ng/dL (normal range, 1.0 to 1.8), and thyroid-stimulating hormone to be < 0.005 u IU/mL (normal range, 0.3 to 4.0). Comptud tomography scan of the chest revealed well-circumscribed soft tissue density mass, 30 mm in size, with a regular periphery in the anterior médiastinum.
Thyroid-directed antibodies were negatives: anti-thyroglobulin antibody, and antimicrosomal antibody. TSH-receptor antibody were positive. Anti-acetylcholine receptor antibodies and prostigmine test were negatives.
The diagnosis of Grave's disease associated to thymoma was made. She was treated with 30 mg per day of Benzylthiouracile (200 mg per day) for several weeks and became clinically euthyroid. Three months later surgery, the anterior mediastinal mass disappeared on a repeat computed tomographic scan of the chest.
Thymic hyperplasia is a common and reversible feature in patients with GD and hyperthyroidism [1, 2]. In most cases, thymic hypertrophy is minimal and unapparent. Therefore, radiologically detectable thymic enlargement as an anterior mediastinal mass with thyrotoxicosis has been infrequently reported. Half of these cases undergo thymectomy because they are suspected of having thymoma. Recognition of the benign nature of TH and its regression following treatment of the hyperthyroidism is important to prevent unnecessary surgical procedures
Michie and Gunn report that approximately 38% of patients with thyrotoxicosis have histologic changes of the thymus gland .
Graves disease is an autoimmune disorder characterized by thyroid enlargement and hyperthyroidism. Thyrotropin receptor (TSHR) autoantibodies bind the TSHR on the membrane of thyroid follicular cells and stimulate cell proliferation and thyroid-hormone synthesis. TSHR has also been identified in extrathyroidal organs, including the human thymus .
Inoue and all conclude that anterior mediastinal mass (AMM) in GD could thus sometimes turn out to be TH and not a thymoma ; however, Levy and Lee noted that GD can also be associated with invasive malignant thymoma [9, 10].
TH is a common feature in GD. However, in most cases, thymic enlargement is minimal, and radiologically detectable massive enlargement of the thymus is infrequently reported. Half of them undergo thymectomy due to the concern about a thymoma .
The differential diagnosis of an AMM includes several malignant lesions with a risk often warranting early surgical excision. In light of the association of benign TH with GD, thymectomy may be delayed in expectation of thymic regression with medical therapy. The timing of regression is variable, and very few reports exist in the literature [1–12].
The mechanism of TH in hyperthyroidism and GD is not well established. Van Herle and Chopra  described that hyperthyroidism persists after thymectomy, and Scheiff and colleagues  reported that administration of triiodothyronine can induce thymic enlargement in mice. Murakami and colleagues  investigated thymic size and density in 23 untreated patients with GD and 38 control subjects using computed tomography. The patients with GD had larger thymic size and higher thymic density than age-matched control subjects. After treatment with anti-thyroid drugs, both thymic size and density were significantly reduced with a concomitant decrease in thyroid-stimulating hormone receptor antibodies. Murakami and colleagues  also clearly showed the presence of thyrotropin receptors in the nonneoplastic thymic tissue by polymerase chain reaction amplification, Northern and Western blot analysis, and immunohistochemistry. These results indicate that TH is apparently associated with GD, and suggest that a thymic thyrotropin receptor may act as an autoantigen that may be involved in the pathophysiology of development of GD.
If an AMM in a thyrotoxic patient is detected on a computed tomographic scan of the chest, and if it is a homogeneous mass with no invasion to the neighboring tissue, and no calcification, no septum, and no cystic lesion, then a high priority should be given to the treatment of the patient's hyperthyroidism under close radiologic follow-up of the AMM. If the size of the mass does not decrease in spite of keeping a euthyroid state for several months, we should take minimal invasive diagnostic maneuvers such as a thoracoscopic procedure or a cervical approach.
'Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.'
- Yacoub A, Gaitonde DY, Wood JC: Thymic hyperplasia and Graves disease: management of anterior mediastinal masses in patients with Graves disease. Endocr Pract 2009, 15:534–9.PubMedView ArticleGoogle Scholar
- Carvalho MR, Dias T, Baptista F, Carmo I: Grave's Disease and massive thymic hyperplasia. Thyroidy 2010, 20:227–229.View ArticleGoogle Scholar
- van Nieuwkoop C, Bolk JH: A mediastinal mass: Graves' disease related thymic hyperplasia. European Journal of Internal Medicine 2005, 16:606–607.PubMedView ArticleGoogle Scholar
- Goichot B, Vinzio S, Massard G, Thompson M: An unusual cause of anterior mediastinal mass: thymic hyperplasia resulting from Grave's disease. Am J Clin Oncol 2006,29(3):322–3.PubMedView ArticleGoogle Scholar
- Budavari AI, Whitaker MD, Helmers R: Thymic Hyperplasia Presenting as Anterior Mediastinal Mass in 2 Patients With Graves Disease. Mayo Clin Proc 2002, 77:495–499.PubMedGoogle Scholar
- Michie W, Gunn A: The thyroid, the thymus and autoimmunity. Br J Clin Pract 1966, 20:9–13.PubMedGoogle Scholar
- Kubicky RA, Faerber EN, de Chadarevian JP, Wu S, Rezvani I, De Luca F: An adolescent with a mediastinal mass, diagnosed with grave's disease and thymic hyperplasia. Pediatrics 2010, (125):e433–7.
- Inoue K, Sugio K, Inoue T, Ishida T, Sugimachi K: Hyperplasia of the thymic gland in a patient with Graves' disease. Ann Thorac Cardiovasc Surg 2000, 6:397–400.PubMedGoogle Scholar
- Levy Y, Afek A, Sherer Y, Bar-Dayan Y, Shibi R, Kopolovic J, Shoenfeld Y: Malignant thymoma associated with autoimmune diseases: a retrospective study and review of the literature. Semin Arthritis Rheum 1998, 28:73–9.PubMedView ArticleGoogle Scholar
- Lee BW, Ihm SH, Shin HS, Yoo HJ: Malignant Thymoma Associated with Myasthenia Gravis, Graves' Disease, and SIADH. Int Med 2008, 47:1009–12.View ArticleGoogle Scholar
- Yamanaka K, Nakayama H, Watanabe K, Kameda Y: Anterior mediastinal mass in a patient with Graves' disease. Ann Thorac Surg 2006, 81:1904–6.PubMedView ArticleGoogle Scholar
- García E, García-Hierro V, Pilar Alvarez M, de la Maza L, Santos E, Pi J, Castillo L, Ruiz E: Thymic hyperplasia in a patient with Graves' disease. Endocrinol Nutr 2009, 56:92–5.PubMedView ArticleGoogle Scholar
- Van Herle AJ, Chopra IJ: Thymic hyperplasia in Graves'disease. J Clin Endocrinol Metab 1971, 32:40–6.View ArticleGoogle Scholar
- Scheiff JM, Cordier AC, Haumont S: Epithelial cell proliferation in thymic hyperplasia induced by triiodothyronine. Clin Exp Immunol 1977, 27:516–21.PubMedGoogle Scholar
- Murakami M, Hosoi Y, Negishi T, et al.: Thymic hyperplasia in patients with Graves' disease: identification of thyrotropin receptors in human thymus. J Clin Invest 1996, 98:2228–34.PubMedView ArticleGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.