Eye sign of hyperthyroidism
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eye signs of hyperthyroidism Graves ophthalmopathy clinical signs
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Eye Signs of Hyperthyroidism
Eye involvement in hyperthyroidism has two distinct categories: (1) sympathomimetic signs that occur with any cause of thyrotoxicosis, and (2) infiltrative/autoimmune signs specific to Graves' disease (Graves' ophthalmopathy).
Part 1: Sympathomimetic Eye Signs (Any Hyperthyroidism)
These result from sympathetic overstimulation of the levator palpebrae superioris and Muller's muscle. They resolve with treatment of the underlying thyrotoxicosis.
| Sign | Description | Mechanism |
|---|---|---|
| Dalrymple's sign | Upper eyelid retraction - sclera visible above the limbus; gives the classic "staring/frightened" expression | Sympathetic stimulation of Muller's muscle |
| Von Graefe's sign (lid lag) | Upper eyelid lags behind the globe on downward gaze - white sclera becomes visible between lid and iris | Delayed relaxation of Muller's muscle |
| Stellwag's sign | Infrequent and incomplete blinking | Sympathetic overactivity |
| Rosenbach's sign | Fine tremor of closed eyelids | Generalised tremor |
| Joffroy's sign | Absence of forehead wrinkling on upward gaze (normally the forehead wrinkles when looking up; in hyperthyroidism the lid is already retracted so no further upward wrinkling occurs) | Upper lid retraction |
| Mobius' sign | Inability to maintain convergence - eyes diverge on bringing an object close to the nose | Weakness of medial recti |
| Boston's sign | Jerky, irregular movement of the upper eyelid on downward gaze (instead of smooth descent) |
Part 2: Graves' Ophthalmopathy (Infiltrative - Specific to Graves' Disease)
Clinically apparent in ~50% of Graves' disease patients. In 75% of these, eye signs appear within one year before or after the diagnosis of hyperthyroidism. It is usually bilateral but can be asymmetrical in up to 15% of cases. Importantly, ophthalmopathy can precede, accompany, or follow thyrotoxicosis by months to years.
Pathophysiology: TSH receptor antibodies cross-react with orbital fibroblasts, causing:
- Accumulation of glycosaminoglycans in orbital tissues
- Lymphocytic infiltration of retro-orbital fat and extraocular muscles
- Swelling of extraocular muscles, proliferation of periorbital fat, and late fibrosis
Clinical features:
- Proptosis (exophthalmos) - forward displacement of the globe due to increased orbital contents. The most recognizable sign.
- Periorbital edema and conjunctival chemosis - venous stasis from orbital vein compression
- Eyelid retraction - upper and/or lower lid retraction (sympathetic + fibrotic)
- Restricted extraocular muscle movement - most commonly inferior rectus (restricted upgaze) and medial rectus; causes diplopia
- Corneal exposure / ulceration - from incomplete lid closure (lagophthalmos), especially at night
- Compressive optic neuropathy - the most serious complication; orbital congestion compresses the optic nerve at the apex, causing visual loss
Symptoms reported by patients: grittiness, excess watering, photophobia, retro-orbital pain, gaze-provoked pain, diplopia, pressure sensation behind the eyes.
Werner's (NOSPECS) Classification of Graves' Ophthalmopathy
| Class | Features |
|---|---|
| 0 | No signs or symptoms |
| 1 | Signs only - eyelid retraction (non-infiltrative) |
| 2 | Soft tissue periorbital swelling, conjunctival edema |
| 3 | Proptosis (exophthalmos) |
| 4 | Extraocular muscle involvement - diplopia |
| 5 | Corneal involvement - exposure keratopathy |
| 6 | Sight loss from optic nerve compression |
Classes 0-1 are non-infiltrative. Classes 2-6 are infiltrative disease.
MRI Appearance
The axial MRI above shows bilateral enlargement of the extraocular muscles - the hallmark of Graves' ophthalmopathy on imaging. The muscle bellies are enlarged while the tendons are typically spared (distinguishing it from orbital myositis where tendons are also enlarged).
Key Points for Exams
- Sympathomimetic signs (lid retraction, lid lag) occur with ANY thyrotoxicosis and are reversible
- Graves' ophthalmopathy is specific to autoimmune thyroid disease and may be irreversible
- The most common muscle affected is the inferior rectus (restriction of upgaze), followed by medial rectus
- Smoking is the strongest modifiable risk factor for Graves' ophthalmopathy, and radioiodine therapy can worsen it (especially in smokers)
- Ophthalmopathy can occur even in euthyroid or hypothyroid patients with Graves' disease
Sources: Tietz Textbook of Laboratory Medicine 7th ed.; Scott-Brown's Otorhinolaryngology Head & Neck Surgery; Bailey & Love's Short Practice of Surgery 28th ed.
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