Graves Ophthalmopathy is the Most Common Cause of Unilateral Proptosis in Adults
The answer is A. Graves ophthalmopathy (thyroid eye disease) is the most common cause of unilateral proptosis in adults, despite being more frequently bilateral.
Key Evidence
Multiple research studies consistently identify thyroid eye disease as the leading etiology. Thyroid eye disease is explicitly stated as "the most common cause of unilateral and bilateral proptosis in adults" 1, with this finding corroborated across multiple sources 2, 3, 4. While Graves ophthalmopathy classically presents bilaterally, unilateral or asymmetric presentation is well-documented and remains the most frequent cause overall 5.
Clinical Reasoning
The ACR Appropriateness Criteria guidelines 6 emphasize that when evaluating unilateral or asymmetric proptosis, the differential includes:
- Thyroid eye disease (most common, can be unilateral or asymmetric)
- Orbital masses (neoplastic processes including lymphoma)
- Vascular malformations
- Inflammatory conditions (IgG4-related disease, idiopathic orbital inflammatory syndrome)
- Carotid-cavernous fistula
The guidelines specifically note that "bilateral exophthalmos may indicate an underlying systemic or diffuse condition, such as thyroid eye disease. Unilateral or asymmetric proptosis is concerning for an underlying mass or pathologic process" 6. However, this statement addresses the differential diagnosis approach rather than epidemiologic frequency—thyroid eye disease remains the most common cause even when presenting unilaterally.
Why Other Options Are Less Common
- Lymphoma (B): While an important consideration requiring MRI with diffusion-weighted imaging 6, it is less frequent than thyroid eye disease
- Periorbital cellulitis (C): Presents acutely with infection signs, not the most common cause of chronic unilateral proptosis
- Cavernous sinus thrombosis (D): Rare, presents with acute severe symptoms including orbital congestion, chemosis, and systemic toxicity
Diagnostic Approach
When thyroid eye disease is suspected with unilateral proptosis, look for:
- Eyelid retraction
- Periorbital edema
- Conjunctival injection and chemosis
- Extraocular muscle restriction
- Exposure keratopathy 1
MRI of the orbits with contrast is the optimal initial imaging 6, revealing enlarged extraocular muscle bellies with tendon sparing—a characteristic finding distinguishing thyroid eye disease from other inflammatory conditions 1.