What is the treatment approach for a patient with hypothyroidism presenting with exophthalmos and apparent hyperthyroid symptoms?

Treatment Approach for Hypothyroid Patient with Exophthalmos and Hyperthyroid Symptoms

This clinical presentation represents thyroid eye disease (TED) occurring in the context of underlying hypothyroidism—a rare but well-documented manifestation of Graves' disease that requires immediate recognition that the exophthalmos and apparent hyperthyroid symptoms are NOT due to hyperthyroidism but rather represent autoimmune orbital inflammation independent of thyroid status. 1, 2

Critical Initial Assessment

The priority is determining whether vision-threatening complications exist, as this dictates urgency of intervention. 1

Immediately evaluate for:

• Compressive optic neuropathy: Check visual acuity, color vision, pupillary responses, visual fields (automated threshold testing), and fundoscopy for disc edema or atrophy 1
• Severe exposure keratopathy: Assess corneal integrity from eyelid retraction and proptosis 1
• Elevated intraocular pressure: Measure IOP, particularly in upgaze 1
• Degree of exophthalmos: Quantify with exophthalmometry 1

Confirm thyroid status with TSH, free T4, and thyroid receptor antibodies (TRAb or TSI)—the presence of positive antibodies with exophthalmos confirms Graves' disease despite hypothyroidism 2

Management Algorithm

Step 1: Optimize Thyroid Status

Continue or initiate levothyroxine to achieve euthyroid state, as maintaining euthyroidism is essential for TED management. 3, 4

• Target euthyroid range with thyroid hormone replacement 1
• Avoid both hypothyroidism and iatrogenic hyperthyroidism, as thyroid dysfunction can worsen TED 5, 4

Step 2: Immediate Supportive Measures (All Patients)

Institute aggressive ocular surface protection immediately. 1

• Ocular lubricants (artificial tears and ointment) are almost always required 1
• Punctal plugs for severe dry eye 1
• Smoking cessation counseling is mandatory—smoking significantly worsens TED severity and progression 1
• Selenium supplementation (if deficient) may reduce inflammatory symptoms in mild TED 1

Step 3: Risk-Stratified Treatment Based on Severity

For Vision-Threatening Disease (Optic Neuropathy or Severe Proptosis):

Refer immediately to orbital specialist and initiate aggressive immunosuppression. 1

• High-dose intravenous corticosteroids followed by oral taper for rapid visual improvement 3
• Orbital decompression surgery is indicated for optic neuropathy with proptosis or when steroids fail 1, 3
• Consider teprotumumab (IGF-1R inhibitor)—reduces proptosis and clinical activity scores in active TED, though relatively contraindicated in inflammatory bowel disease and absolutely contraindicated in pregnancy 1
• Orbital radiation may be considered in select cases, particularly if patient is not a surgical candidate 1, 3

For Moderate-to-Severe Active TED (Without Vision Threat):

Teprotumumab represents the most effective medical therapy for reducing proptosis and inflammation. 1

• Teprotumumab infusions have shown reduction in extraocular muscle size, proptosis, and diplopia scores 1
• Alternative biologics (tocilizumab, rituximab) used in Europe if teprotumumab unavailable 1
• High-dose pulse steroids or orbital radiation for persistent symptoms 1

For Mild TED:

Conservative management with close monitoring. 1, 3

• Supportive care with lubricants and selenium supplementation 1
• Monitor every 6-8 weeks for progression to moderate-severe disease 1
• Prisms (Fresnel or ground-in) for diplopia management 1

Step 4: Surgical Planning (After Disease Stabilization)

Surgery should only be performed after TED has been inactive for at least 6 months, with stable measurements. 1, 3

The surgical sequence must follow this order:

1. Orbital decompression first (if needed)—changes alignment and worsens proptosis if done after muscle surgery 1, 3
2. Strabismus surgery second—wait 6 months after decompression as alignment changes 1, 3
3. Eyelid surgery last—vertical muscle surgery can alter lid position 3

Critical Pitfalls to Avoid

Do not attribute the exophthalmos to the hypothyroidism itself—this represents Graves' orbitopathy occurring independently of thyroid hormone levels 2. The coexistence is rare but well-documented 6, 2.

Do not use radioactive iodine therapy in this patient—RAI is associated with TED progression and should be avoided when TED is present, particularly in moderate-to-severe cases 4

Do not delay endocrinology and ophthalmology (orbital specialist) referral—collaborative management is essential 1

Do not perform strabismus surgery during active inflammatory phase—wait for quiescence (stable measurements for 6 months minimum) 1, 3

Monitoring Protocol

• Visual function monitoring: Acuity, color vision, visual fields, and fundoscopy at each visit 1
• Exophthalmometry: Serial measurements to track progression 1
• Thyroid function: Monitor TSH and free T4 to maintain euthyroid state 1
• Orbital imaging (CT or MRI): Baseline and as needed to assess muscle enlargement, orbital apex crowding, and treatment response 1