Can Graves' disease or treatment with carbimazole (antithyroid medication) cause lung changes, including asymmetric cystic-like lesions or cavities, as seen on a computed tomography (CT) chest scan in a patient with a history of Graves' disease?

Graves' Disease and Carbimazole Do Not Cause Asymmetric Cystic Lung Lesions

Neither Graves' disease nor carbimazole treatment causes asymmetric cystic-like lesions or cavities on CT chest imaging. These findings require urgent investigation for alternative diagnoses, particularly histiocytic neoplasms (Erdheim-Chester disease), chronic pulmonary aspergillosis, or drug-related pneumonitis from other medications.

Why Graves' Disease Is Not the Cause

Graves' disease does not produce pulmonary parenchymal abnormalities. The only thoracic manifestation of Graves' disease is thymic hyperplasia, which presents as a mediastinal mass that spontaneously regresses with treatment of thyrotoxicosis 1. This appears as soft tissue enlargement in the anterior mediastinum, not as cystic or cavitary lung lesions.

• Graves' disease affects the thyroid gland and can cause orbital pseudotumors, but pulmonary involvement is not a recognized feature 2
• When Graves' disease is mentioned in differential diagnoses within the provided guidelines, it refers specifically to orbital manifestations that mimic other conditions, not pulmonary disease 2

Why Carbimazole Is Not the Cause

Carbimazole is an antithyroid medication used to treat Graves' disease and does not cause pulmonary cystic lesions or cavities 3, 4, 5.

• The literature on carbimazole focuses on its efficacy in controlling thyrotoxicosis and potential drug resistance, with no reports of pulmonary toxicity causing cystic or cavitary changes 3, 4
• Drug-related pneumonitis from molecular targeting agents and immune checkpoint inhibitors can cause various CT patterns (ground-glass opacities, consolidation, organizing pneumonia), but not asymmetric cystic lesions or cavities 2

Critical Alternative Diagnoses to Consider

Erdheim-Chester Disease (ECD)

This is the most important diagnosis to exclude given the CT findings described. ECD is a histiocytic neoplasm that commonly affects the lungs and can present with asymmetric involvement.

• Pulmonary involvement occurs in approximately 50% of ECD cases, manifesting as mediastinal infiltration, pleural thickening, interlobular septal thickening, ground-glass opacities, nodules, or cysts 2, 6
• Unlike pulmonary Langerhans cell histiocytosis, ECD has no association with cigarette smoking 2
• ECD can coexist with Graves' disease as part of its multi-system involvement, particularly affecting the orbit where it mimics Graves' ophthalmopathy 2
• Diagnosis requires: bilateral symmetric osteosclerosis of long bones on bone scan (95% of cases), positive CD68 immunohistochemistry on biopsy, and BRAF V600E mutation testing (positive in 50-70%) 2, 6

Chronic Pulmonary Aspergillosis

Asymmetric cavitary lesions with irregular walls are characteristic of chronic cavitary pulmonary aspergillosis.

• CT findings include one or more cavities with irregular walls, fungal balls within cavities, and thickened pleura 2
• Diagnosis requires: positive Aspergillus IgG or precipitins (>90% sensitive), Aspergillus antigen or DNA in respiratory fluids, or biopsy showing fungal hyphae 2
• Risk factors include prior tuberculosis, COPD, or other chronic lung disease 2

Langerhans Cell Histiocytosis (LCH)

Pulmonary LCH presents with cystic changes but has a strong association with cigarette smoking (unlike ECD).

• CT shows cysts and nodules, typically in upper and mid-lung zones with relative sparing of costophrenic angles 2
• Bronchoscopic biopsy with CD1a staining >5% is diagnostic 6

Diagnostic Algorithm

1. Obtain high-resolution CT chest with contrast to fully characterize the cystic/cavitary lesions, assess distribution (upper vs. lower lung, symmetric vs. asymmetric), and identify associated findings (pleural thickening, mediastinal infiltration, ground-glass opacities) 2, 7

2. Perform full-body imaging with FDG-PET-CT or technetium-99m bone scintigraphy to assess for bilateral symmetric long bone involvement (pathognomonic for ECD) 2

3. Send Aspergillus serology (IgG and precipitins) and respiratory samples for Aspergillus antigen, DNA, and culture 2

4. Obtain bronchoscopic or surgical lung biopsy for definitive histopathologic diagnosis with immunohistochemistry (CD68 for ECD, CD1a for LCH) and fungal stains 2, 6

5. Test for BRAF V600E mutation if histiocytic neoplasm is suspected 6

6. Review complete medication history for fibrogenic drugs (amiodarone, methotrexate, nitrofurantoin, EGFR-TKI, mTOR inhibitors, immune checkpoint inhibitors), though these typically cause ground-glass opacities or organizing pneumonia patterns, not cystic lesions 2, 7

Critical Pitfalls to Avoid

• Do not attribute cystic lung lesions to Graves' disease simply because the patient has a history of this condition—there is no pathophysiologic mechanism linking Graves' disease to pulmonary cysts or cavities
• Do not dismiss these findings as drug-related pneumonitis from carbimazole without systematic exclusion of histiocytic neoplasms and fungal infection, as carbimazole does not cause this CT pattern 2, 3
• Do not delay biopsy if initial non-invasive testing is unrevealing, as definitive histopathologic diagnosis is essential for appropriate management of histiocytic neoplasms 2
• Consider that ECD can mimic Graves' disease in the orbit, so patients may have been misdiagnosed or have dual pathology 2