What is the recommended management for an adult with active thyroid eye disease and positive TSH‑receptor antibodies?

Management of Active Thyroid Eye Disease with Positive TSH-Receptor Antibodies

For an adult with active thyroid eye disease and positive TSH-receptor antibodies, initiate treatment based on disease severity: teprotumumab for moderate-to-severe active disease (Clinical Activity Score ≥3), ocular lubricants and smoking cessation for mild disease, and urgent orbital decompression for sight-threatening complications. 1, 2

Initial Assessment and Risk Stratification

Measure the Clinical Activity Score (CAS) immediately to determine disease activity and guide treatment intensity. 1 A CAS ≥3 indicates active inflammation requiring therapeutic intervention beyond conservative measures. 1

• Document baseline proptosis using exophthalmometry, assess for diplopia in primary gaze and reading position, and screen for compressive optic neuropathy with visual acuity, color vision, visual fields, pupillary examination, and fundus examination. 3, 1
• Obtain orbital CT or MRI to confirm tendon-sparing extraocular muscle enlargement (most commonly inferior and medial rectus) and quantify proptosis. 3, 1
• Verify thyroid function is controlled or within 50% of normal limits before initiating immunosuppressive therapy. 2

The presence of TSH-receptor antibodies correlates directly with disease activity (CAS) and proptosis severity, confirming the autoimmune pathogenesis and supporting aggressive treatment in active disease. 4, 5

Treatment Algorithm by Disease Severity

Mild Disease (CAS <3, no diplopia in primary gaze, no optic neuropathy)

• Prescribe artificial tears and lubricating ointments regularly to prevent exposure keratopathy from lid retraction and mild proptosis. 3, 1
• Consider punctal plugs to improve tear retention. 3, 1
• Mandate immediate smoking cessation; smoking dramatically worsens disease severity and prognosis. 3, 1, 6
• Supplement selenium in patients with documented selenium deficiency to reduce inflammatory symptoms through antioxidant effects. 3, 6
• Observe closely without immunosuppression as long as the clinical picture remains stable. 1

Moderate-to-Severe Active Disease (CAS ≥3)

Teprotumumab is the first-line treatment for moderate-to-severe active thyroid eye disease, demonstrating superior proptosis reduction compared to intravenous methylprednisolone. 2, 7

• Administer teprotumumab 10 mg/kg IV for the first infusion, then 20 mg/kg IV every 3 weeks for 7 additional infusions (8 total infusions over 24 weeks). 2
• Expect proptosis improvement as early as 6 weeks, with 71–83% of patients achieving ≥2 mm proptosis reduction by week 24. 2
• Counsel patients about hearing risk before treatment; 30% experience hearing loss that may be permanent. 1, 7
• Establish baseline audiometry and monitor throughout treatment. 1
• Teprotumumab also improves diplopia: 53% of patients with baseline diplopia achieve complete resolution by week 24. 2

In regions where teprotumumab is unavailable or cost-prohibitive, intravenous methylprednisolone remains an acceptable alternative, though less effective for proptosis reduction. 7

• Tocilizumab (interleukin-6 receptor blocker) is an effective option for steroid-resistant cases. 7

Sight-Threatening Disease (Compressive optic neuropathy or severe exposure keratopathy)

Urgent orbital decompression, high-dose corticosteroids, or orbital radiation must be initiated immediately for compressive optic neuropathy or corneal ulceration despite maximal lubrication. 3, 1

• Do not delay decompression surgery while attempting medical therapy in the presence of vision loss, afferent pupillary defect, or color vision abnormalities. 3, 1

Surgical Sequencing for Rehabilitation

Surgery must be delayed until the inflammatory phase has subsided and the angle of strabismus deviation has been stable for at least 6 months. 1

When multiple surgical interventions are needed, follow this mandatory sequence: 1

1. Orbital decompression first (if needed for persistent proptosis after medical therapy) 1
2. Strabismus surgery second to address diplopia, because decompression predictably worsens or creates new strabismus 3, 1
3. Eyelid surgery last to correct retraction, as earlier surgeries alter lid position 1

• Recession of restricted muscles (especially inferior rectus) is the mainstay of strabismus correction; avoid resection in restrictive disease. 1
• Counsel patients preoperatively that muscle recession surgery predictably worsens proptosis, necessitating decompression consultation in patients with concurrent significant proptosis. 3, 1

Monitoring TSH-Receptor Antibody Levels

Serial TSH-receptor antibody measurements guide disease management and predict reactivation risk. 8

• Antibody levels vary with time, correlate with disease activity (CAS), and are affected by smoking and endocrine control. 8
• Surgical thyroidectomy reduces antibody levels and lowers TED reactivation rates compared to radioactive iodine ablation, which increases orbitopathy risk by leaving the stimulating antigen in situ. 8
• High antibody titers at presentation predict more severe disease and warrant closer monitoring. 6, 4

Critical Pitfalls to Avoid

• Do not initiate strabismus surgery during active inflammation (CAS ≥3); the deviation will continue to change. 1
• Do not perform eyelid surgery before strabismus repair; muscle surgery alters lid position. 1
• Do not underestimate the complexity of vertical deviations, particularly inferior rectus involvement, which has lower surgical success rates (66%) than horizontal deviations (84%). 1
• Do not start immunosuppressive therapy for truly mild disease without progression; the benign natural history does not justify adverse effects. 1
• Do not overlook co-existent myasthenia gravis; perform forced-duction testing to differentiate mechanical restriction (positive test in TED) from fatigable weakness (negative test in MG). 9

Multidisciplinary Coordination

Coordinate care among endocrinology (to achieve and maintain euthyroid state), oculoplastics (for decompression and lid surgery), and neuro-ophthalmology (for optic neuropathy surveillance). 1

• Ensure thyroid function remains controlled throughout treatment; high free T3 and T4 levels worsen eye symptoms. 6
• Male gender, older age, diabetes, hypercholesterolemia, and duration of hyperthyroidism are additional risk factors for severe disease. 6, 7