Which thyroid disease causes exophthalmos?

Graves' Disease is the Primary Thyroid Disorder Causing Bulging Eyes (Exophthalmos)

Graves' disease is the most common thyroid disorder that causes exophthalmos (bulging eyes), affecting approximately 0.5% of the US population and accounting for 80% of bilateral exophthalmos cases. 1 This condition is part of an autoimmune process that affects multiple systems, most notably the thyroid gland and orbital tissues.

Pathophysiology of Thyroid Eye Disease

Thyroid eye disease (TED) is an autoimmune disorder characterized by:

• Inflammation and congestion of orbital tissues
• Enlargement of extraocular muscles
• Increased orbital fat volume
• Soft tissue congestion with enlargement of preseptal fat pads
• Eyelid retraction
• Exophthalmos (proptosis)
• Restrictive extraocular myopathy
• Potential optic neuropathy 2

The condition results from autoimmune activity primarily affecting the orbit and surrounding tissues, causing inflammatory edema initially, followed by fibrosis in later stages.

Association with Thyroid Function

While Graves' disease with hyperthyroidism is the most common association with exophthalmos, it's important to note that TED can occur with various thyroid states:

• Most commonly associated with hyperthyroidism (Graves' disease)
• Can also occur with normal-functioning thyroid
• Can occur with under-functioning thyroid (e.g., Hashimoto's thyroiditis) 2

In fact, thyroid ophthalmopathy may precede or follow the onset of hyperthyroidism by many years, though the majority of patients experience thyroid dysfunction and eye disease within 18 months of each other 2.

Clinical Presentation

The clinical manifestations of TED include:

• Exophthalmos (bulging eyes)
• Eyelid retraction
• Periorbital edema and erythema
• Exposure keratopathy (corneal damage from exposure)
• Extraocular muscle enlargement
• Diplopia (double vision) due to restrictive myopathy
• Potential compressive optic neuropathy in severe cases
• Possible globe subluxation 2

The most frequently affected muscles in TED are:

1. Inferior rectus (most common)
2. Medial rectus (second most common)
3. Other rectus muscles (less common but possible) 2

Epidemiology and Risk Factors

TED shows clear demographic patterns:

• Incidence: 16 per 100,000 per year in women; 2.9 per 100,000 per year in men
• Female predominance: 8:1 female-to-male ratio
• Most common onset: fourth to fifth decade of life
• Between 30-50% of patients with TED develop restrictive myopathy 2

Key risk factors include:

• Smoking
• Diseases causing reduced oxygen saturation (e.g., emphysema)
• Exposure to ionizing radiation
• Radioactive iodine treatment
• High anti-thyroid antibody titers
• Serum vitamin D deficiency
• Family history of thyroid disease 2

Diagnostic Approach

When evaluating a patient with suspected TED:

• Measure exophthalmos using an exophthalmometer
• Perform a complete sensorimotor examination to detect restrictive strabismus
• Check for signs of optic neuropathy (visual acuity, color vision, visual fields)
• Assess for eyelid retraction and exposure keratopathy
• Consider orbital imaging (CT or MRI) to evaluate extraocular muscle enlargement and orbital apex crowding
• Check thyroid function tests and thyroid antibodies 2

Clinical Pitfalls to Avoid

1. Don't assume normal thyroid function excludes TED: Patients can have exophthalmos with euthyroid or hypothyroid states.

2. Don't overlook optic neuropathy: This vision-threatening complication requires urgent intervention.

3. Don't miss coexisting myasthenia gravis: The incidence is increased in patients with TED.

4. Don't perform strabismus surgery before orbital decompression: If orbital decompression is needed, it should precede strabismus surgery as decompression can significantly alter ocular alignment.

5. Don't forget to counsel patients about smoking cessation: Smoking significantly worsens TED outcomes and severity.

Treatment Considerations

Treatment of TED is symptom-directed, with goals including:

• Prevention of vision loss from optic neuropathy or exposure keratopathy
• Management of diplopia and ocular misalignment
• Reduction of exophthalmos
• Improvement of quality of life 2

In severe cases with significant proptosis or optic neuropathy, orbital decompression, high-dose steroids, or radiation treatment may be necessary 2.

For patients with mild disease, selenium supplementation may help reduce inflammatory symptoms, particularly in those with selenium deficiency 3.