Multi-disciplinary collaboration in diagnosing thymic hyperplasia in a Graves’ disease patient

Abstract

Summary

Thymic hyperplasia in Graves’ disease is rarely identified due to the absence of routine imaging, but not uncommonly present. It is usually seen when imaging is performed for other reasons. Despite thymic hyperplasia becoming a more commonly identified occurrence, follow-up imaging scans and multi-disciplinary team (MDT) approach are still recommended to distinguish this benign transformation from more significant differentials. These steps can lead to distress in patients. Therefore, clinicians and radiologists being aware of this correlation between thymic hyperplasia and Graves’ disease can add reassurances about the most likely diagnosis whilst the patient is undergoing limited further investigation to rule out differentials and subsequently, avoid unnecessary intervention. Here, we report a case of Graves’ disease with thymic hyperplasia in a young woman who initially presented with non-specific eye symptoms and incidental mediastinal mass, in which involvement of multiple speciality teams was important to rule out thymoma and myasthenia gravis (MG).

Learning points

1. Although Graves’ disease with thymic hyperplasia is not uncommon, it is sometimes difficult to diagnose with one imaging scan due to the overlap of radiological characteristics of other important differentials; an MDT discussion and further imaging scans are needed to confirm the diagnosis in some cases.

2. Getting MDT involvement early would quickly assist in ruling out more significant differentials and avoid unnecessary surgical intervention by concluding thymic hyperplasia.

3. Clinicians having knowledge on the relation between Graves’ disease and thymic hyperplasia may reassure the patient by explaining the possible resolution with treatment, while awaiting further MDT discussion.

4. To rule out ocular MG in Graves’ disease patients, additional investigations and neurology referral are often required as the serum antibody tests are less sensitive in ocular MG than generalised MG.

Background

Graves’ disease is known to have affiliation with other autoimmune diseases such as myasthenia gravis (MG), type 1 diabetes mellitus and vitiligo. (1, 2) It is also known to be associated with thymic hyperplasia, which is rarely identified (2, 3). The exact cause of why Graves’ disease can have thymic hyperplasia is not yet found (2). When patients with Graves’ disease become euthyroid, the thymic hyperplasia resolves (2). It is important that healthcare professionals recognise not only this likely connection and its benign nature but also appropriate steps to take to rule out more significant differentials. In our case, instead of the typical Graves’ symptoms, the patient presented with non-specific thyroid eye disease symptoms; hence, she had additional imaging that highlighted thymic change.

Case presentation

A 34-year-old lady, who was previously fit and well, initially had presented to optician and ophthalmology team with left-sided ptosis, with diurnal variation, but without exophthalmos and normal eye movement. Due to her eye changes, initial routine blood tests were done at her GP surgery. She was later referred to our endocrine clinic as her bloods came back as overactive thyroid.

Investigation

Her initial blood test showed free T4 (fT4): 40.2 pmol/L (12–22), free T3 (fT3): 21.2 pmol/L (3.1–6.8), thyroid-stimulating hormone (TSH): <0.05 mIU/L (0.3–5.5) and TSH receptor antibodies (TRAb): 8.12 IU/L (0–1.75). Due to her non-specific eye symptoms, her GP also requested Ach Ab and anti-MUSK Ab, which were reported negative. An MRI head and neck was performed to rule out causes of Horner’s syndrome, which incidentally found an abnormal superior anterior mediastinal soft tissue mass. Patient was understandably overwhelmed by the new diagnosis of Graves’ disease and the incidental finding of mediastinum soft tissue mass. A CT chest was performed to get more understanding of the mass. Her CT thorax with contrast initially reported a 23 × 20 mm soft tissue retrosternal solid and cystic lesion was seen in anterior superior mediastinum, likely thymoma.

Her case was discussed in head and neck multi-disciplinary team (MDT) and radiologists concluded that the CT finding was not representative of thymoma and advised to continue with the treatment of Graves’ disease. A homogeneous triangular soft tissue anterior mediastinal mass is appreciated (Fig. 1A), confined to the anterior mediastinal borders laterally and draped over the pericardium inferiorly (Fig. 1B), with no evidence of infiltration. Faint streaky low attenuation throughout is in keeping with symmetrical widespread fat infiltration. After the MDT discussion, an addendum was added to her CT report as thymic hyperplasia. Patient was also reviewed by a thoracic surgeon, who reassured and confirmed her that the anterior mediastinal soft tissue mass was likely to be reactive thymic hyperplasia. No surgical intervention was needed as it was benign in nature and arranged a repeat MRI in 1 year’s time while continuing to treat her Graves’ disease.

Figure 1.

CT images of homogeneous triangular soft tissue anterior mediastinal mass confined to the anterior mediastinal borders laterally and draped over the pericardium inferiorly, with no evidence of infiltration.

In addition, the patient was seen by the ophthalmology team who thought her eye lid abnormality was likely to represent thyroid eye disease but referred her to the neurology team to fully rule out MG due to diurnal variation of her left-sided ptosis. She was seen by the neurology team, who confirmed that there was no neurophysiological evidence to support a diagnosis of ocular MG. Her left partial ptosis with diurnal variation was concluded as medically unexplained, given negative serum acetylcholine receptor and Musk IgG Ab along with normal nerve conduction study/electromyography.

Treatment

After discussing different options of treatment for Graves’ disease, she was started on carbimazole and titrated accordingly by the endocrine team.

Outcome and follow-up

After having completed 12 months of down titrated carbimazole, the patient remained clinically and biochemically euthyroid, without anti-thyroid medication. MR imaging was performed 12 months later due to the reassuring CT appearances. This demonstrated significant reduction in thymic size, with a minimal residual soft tissue component, best appreciated on the out of phase sequence (Fig. 2). Therefore, a confident diagnosis of thymic hyperplasia could be made, with no further imaging recommended. She was also followed-up with thoracic surgeon who reviewed her follow-up MRI scan, which showed near complete resolution of reactive thymic hyperplasia with no evidence of thymoma. Her previous reactive thymic hyperplasia was secondary to Graves’ disease and now that she became euthyroid, it was resolved, and the patient was discharged from the thoracic clinic.

Figure 2.

MR images showing significant reduction in thymic size, with a minimal residual soft tissue component, best appreciated on the out of phase sequence.

Discussion

Thymic hyperplasia linked with Graves’ disease is usually discovered incidentally as a mediastinal mass on chest imaging, which is performed for unrelated symptoms, since we do not routinely image this in Graves’ disease (4). The exact mechanism of why Graves’ disease can have thymic hyperplasia is not clearly understood; thymic hyperplasia is more likely resulted from Graves’ disease, although earlier literature suggested that hyperplastic thymus could be a cause by being crucial in distinguishing self from non-self for T cell recognition (2, 5). In a study by Murakami et al., it was concluded that thymic thyrotropin receptor may contribute to the development of thymic hyperplasia in patients with Graves’ disease by acting as an autoantigen (2, 6).

Radiologically, thymic hyperplasia often has a characteristic appearance, that of a diffuse enlargement of the gland, a homogeneous triangular anterior mediastinal mass with well-defined slightly concave borders abutting the pleural surfaces. Streaky fat may be seen throughout the gland, although intracytoplasmic fat that is characteristic for thymic hyperplasia is usually not appreciable on CT (7). Given the overlap in radiographic appearances of thymic hyperplasia and both thymoma and lymphoma, further imaging may be required for tissue characterisation, either with PET-CT or with MR. The latter utilises T1 and T2 weighted imaging to confirm the presence of fluid filled cystic components, in addition to chemical shift sequences that identify intracytoplasmic fat. An advantage of this technique is that it does not use ionising radiation, particularly beneficial in younger patients. Importantly, the thymus may appear larger on MR than on contemporaneous CT, due to their margins being better delineating, especially if they contain fat (7). Histologically, two different types of histological findings can be found in the thymic hyperplasia associated with Graves’ disease; lymphoid thymic hyperplasia due to autoimmune processes and true thymic hyperplasia due to excessive thyroid hormones (8). However, in cases of thymic hyperplasia which are associated with Graves’ disease and which do not have any suspicious radiological findings, invasive diagnostic procedures are usually not needed (8).

There is no definitive treatment to manage thymic hyperplasia in Graves’ disease patients (9). As the thymus usually regresses 6 months after controlling the Graves’ disease itself, observation while continuing treatment for Graves’ disease is suggested (9). Therefore, clinicians having knowledge on the relation between Graves’ disease and thymic hyperplasia and how it can be spontaneously resolved can help reassure patients and guide with management (2). In our patient, her reactive thymic hyperplasia has gone near complete resolution when she became euthyroid, as evident through a follow-up MRI after 1 year of treatment. Her only treatment was carbimazole, which was titrated according to her thyroid function tests.

Moreover, interestingly, in our patient, her left-sided ptosis with diurnal variation along with incidental finding of thymic change had led the ophthalmologist to refer to neurologist to further rule out the MG. It has been reported that 0.2% of patients with thyroid disease, especially thyrotoxicosis, have associated MG (10). Due to the possible co-existence between the two autoimmune conditions, it is important to exclude ocular MG in thyroid eye disease patients presenting with variability and fatigue (11). It is worth mentioning that additional investigations such as electrophysiologic test/EMG and thymic imaging scans and neurology referral are needed to rule out ocular MG, as the serum antibody tests are often less sensitive in ocular MG (30–77%) than generalised MG (80–99%) (11, 12).

To conclude, it is important that clinicians be aware of the benign association of thymic hyperplasia and Graves’ disease and conservative approach in these cases including radiological follow-up (8). Moreover, we would like to highlight that multiple speciality involvement was crucial in excluding important differentials and diagnosing thymic hyperplasia in our patient.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the work reported.

Funding

This work was partially supported by Derby and Burton Hospitals Charity Finance Team from Derby and Burton Hospital Charities (approval number: TI250435).

Patient consent

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient.

Author contribution statement

K Y Kyaw helped in draughting of the work, literature review, reviewed and edited most of the manuscript. M T Lwin helped in draughting of the work and literature review. A Gummow helped with radiological evaluation and literature review. A Ugur provided clinical care, reviewed and edited the manuscript and gave approval of the final version of the manuscript.