Thymic hyperplasia is characterised by a generally diffuse and symmetrical increase in the size of the thymus, which may be caused by epithelial cell proliferation or increased lymphoid follicles in this organ. It may be an incidental finding or alternatively manifest compressive or systemic symptoms. Its association with several autoimmune diseases, including myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis and, above all, Graves' disease, has been reported.1 We present a case of transient thymic hyperplasia, incidentally found, associated with silent or painless thyroiditis.
This was a 51-year-old female patient, a one pack-a-day smoker, with no other relevant medical or surgical history, who was examined by the Pulmonology department due to a one-year history of asthma-like symptoms, with night-time coughing and wheezing fits, exertional dyspnoea and recurrent bronchitis. During the medical interview, she reported symptoms of nervousness, irritability and 5-kg weight loss in two months without a reduction in dietary intake. The patient's blood test results revealed hyperthyroidism with thyrotropin or thyroid-stimulating hormone (TSH) below 0.01 uIU/mL (normal range 0.38–5.33) and free thyroxine (T4) 2.49 ng/dl (0.38–1.5), while she was positive for thyroid peroxidase antibodies (428.3 IU/mL, normal value below 10) and negative for TSH receptor antibodies (thyroid stimulating immunoglobulin [TSI]). A thyroid ultrasound was requested, which showed glandular parenchyma with decreased echogenicity, a heterogeneous structure and a pseudonodular appearance, and a chest X-ray, which revealed mediastinal widening. In light of these findings, a computed tomography (CT) of the chest was performed, which incidentally revealed a vascularised solid mass in the anterior and superior mediastinum measuring 44 × 24 mm, consistent with a thymoma (Fig. 1A). The study was completed with a positron emission tomography (PET/CT) scan that identified a high-uptake lesion in the anterior mediastinum, consistent with thymic hyperplasia, and bilateral and diffuse high thyroid uptake (Fig. 1B). A diagnosis of hyperthyroidism probably associated with Graves' disease was established, and treatment with thiamazole 10 mg/day was started. Once blood test results and incompatible clinical symptoms had ruled out myasthenia gravis, a watchful waiting approach was adopted to the mediastinal lesion following assessment for thoracic surgery. After two months of follow-up, the patient quickly developed hypothyroidism, leading us to change our diagnosis to probable subacute lymphocytic thyroiditis given the marked reduction in free T4, and antithyroid medication was suspended. After six months, thyroid hormone levels returned to normal and a follow-up CT scan found no trace of the mediastinal lesion (Fig. 1C).
Although rare, the onset of thymic hyperplasia in patients with Graves' disease is well documented and has been reported in over one hundred cases published in the scientific literature.1–4 The prevalence of this association is probably underestimated given that routine imaging studies for its detection are not performed. Its pathogenesis is related both to hyperthyroidism itself as well as to an autoimmune mechanism. On the one hand, thyroid hormones could stimulate thymus growth, particularly the epithelial component and cortical lymphoid tissue through the action of local regulatory proteins such as thymulin, while on the other, TSH receptors have been found in the thymus, in addition to in the orbit or in the dermis of the pretibial region, whose direct stimulation by TSI could induce cell proliferation.1,2,5 It has also been hypothesised that inflammatory cytokines may induce increased angiogenesis in this organ in Graves' disease patients.2 Thymic hyperplasia has a benign clinical course and is asymptomatic in the majority of cases. A differential diagnosis must be performed with other lesions located in the anterior mediastinum such as thymomas, germ cell tumours or mesenchymal tumours, lymphomas, masses of thyroid or parathyroid origin or metastases. Recognising its radiological features is therefore essential (thymic hyperplasia is homogeneous, is not accompanied by cystic areas or calcifications and it does not invade neighbouring structures), as is close monitoring, as it almost always remits during Graves' disease treatment and once the thyroid profile has returned to normal.1,6 As such, biopsy or surgical removal are not usually required, but it is recommended to perform a follow-up CT scan six months after normal thyroid function is restored.1
The unusual aspect of our case is that the finding of thymic hyperplasia is not associated with Graves' disease but rather with thyroiditis. The absence of goitre and ophthalmopathy, negativity for TSI, elevated thyroid peroxidase antibodies and the clinical course, with rapid resolution of hyperthyroidism, point to a diagnosis of silent or painless subacute lymphocytic thyroiditis or hashitoxicosis, which have rarely been associated with thymic hyperplasia in the literature.
The pathogenic mechanism of thyroid growth in this context is probably related to the transient increase in thyroid hormones. In this regard, cases of thymic hyperplasia in association with other thyroid disorders, such as follicular neoplasms, have also recently been published.7,8 It is therefore essential to be aware of these associations and to conduct comprehensive thyroid function tests in all patients with lesions and masses in the anterior mediastinum.