An Adolescent With a Mediastinal Mass, Diagnosed With Graves Disease and Thymic Hyperplasia

Abstract

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. Thus far, radiologically detectable thymic enlargement has only been reported in adults with Graves disease. We present here the case of a child with Graves disease and significant thymic hyperplasia. L. K. was a 15-year-old girl evaluated for cough and dyspnea on exertion. A chest radiograph was obtained, and it revealed a widened superior mediastinum. A computed-tomography scan of her chest identified a mass in the anterior mediastinum without associated lymphadenopathy. Because of these radiologic findings and her weight loss, she was referred to the oncology service; a biopsy of the mediastinal mass was obtained and revealed thymic reactive hyperplasia. Because of persistent tachycardia, thyroid studies were obtained, and the diagnosis of Graves disease was established. The child's physical examination revealed a minimally enlarged thyroid gland and no exophthalmos. One month after medical treatment was initiated, a repeat computed-tomography scan of her chest identified significantly reduced thymic size. To our knowledge, this is the first pediatric patient reported with Graves disease and significant thymic enlargement. Considering the diagnosis of Graves disease for a child with an anterior mediastinal mass and without the typical physical findings of autoimmune hyperthyroidism (goiter, exophthalmos) may prevent unnecessary diagnostic studies and their associated financial and emotional costs.

Genetics of Graves’ Disease: Special Focus on the Role of TSHR Gene

“…2). This latter finding was recently confirmed by Van der Weerd and collaborators [112]. The level of TSHR expression in thymocytes indicated that thymocytes are the major contributors to total thymic TSHR expression.…”

“…Do TSHR + thymocytes contribute to central tolerance failure in GD? The publication by de Weerd et al, demonstrated that TSHR expressed by thymocytes is functional, and TSH enhanced T-cell development in an in vitro co-culture system [112]. We have recently found that TSHR expression is confined to the developing T cells within the thymus (and not in the peripheral T cells) and strictly linked to the maturation process of thymocytes.…”

“…Since then, an increasing number of studies confirmed that TSHR is expressed in the thymus [89,107,112,113]. The level of TSHR expression in the thymus is between 5 to 50-fold lower than in thyroid [89,112,113].…”

Reversible Left Recurrent Laryngeal Nerve Palsy in Pediatric Graves’ Disease

“…[9][10][11] Thyrotropin receptors are present in the thymus and, when stimulated by the anti-thyrotropin receptor antibodies present in Graves' disease, may result in thymic hyperplasia, 12 which has been described in pediatric Graves' disease. 13 In vivo data suggest an immunologic effect of antithyroid drugs such as methimazole. Use of an antithyroid drug…”

Thymic hyperplasia in patients with Graves’ disease

“…Thirty-five of these patients had a thymic mass that shrank under medical treatment for GD [9]. Thymectomy was performed in 11 patients and histology revealed: one case of reactive thymic hyperplasia [10]; two cases of thymic lymphoid hyperplasia with an increase in the number of lymphoid follicles revealing germinal centers largely composed of B lymphocytes (Mic2 and CD79a positive), and an increased content of Hassall's corpuscles showing keratin staining [11,12]; and one case of true thymic hyperplasia [12]. The limit of this review [9] lies in that it is only a collection of case reports and includes no large epidemiological studies, so the question of the real frequency of TH in GD remains unanswered.…”