What are the evaluation and treatment options for bulging eyes and a palpable thyroid?

Evaluation and Management of Bulging Eyes with Palpable Thyroid

This presentation is highly suggestive of thyroid eye disease (TED) associated with Graves' disease, requiring immediate thyroid function testing, ophthalmologic evaluation, and initiation of antithyroid medication if hyperthyroidism is confirmed. 1, 2

Initial Diagnostic Workup

Laboratory Testing

• Measure TSH and Free T4 immediately to assess thyroid status, as the combination of exophthalmos and palpable thyroid strongly suggests Graves' disease 3, 2
• Order TSH receptor antibodies if clinical features suggest Graves' disease, as these are detectable in >95% of TED patients and directly correlate with disease activity and severity 4, 2
• Check antithyroid peroxidase antibody and antithyroglobulin antibody for thyroid eye disease confirmation 3

Imaging Studies

• Thyroid ultrasound is the preferred first-line imaging to characterize the palpable thyroid abnormality and assess for nodules or diffuse enlargement 3
• Orbital CT or MRI should be obtained to assess extraocular muscle thickening (particularly inferior and medial rectus muscles) and orbital fat enlargement, which are hallmarks of TED 3, 1, 2
• CT is preferred over MRI due to less respiratory motion artifact 3

Ophthalmologic Assessment

• Measure proptosis by exophthalmometry to establish baseline and quantify severity 1
• Document Clinical Activity Score (CAS) ranging from 0-7, with scores ≥3 indicating active inflammation requiring treatment 1, 5
• Screen for optic neuropathy with visual acuity, color vision, visual fields, pupillary exam, and fundus examination, as compressive optic neuropathy is sight-threatening 1, 2
• Assess for diplopia using standardized grading, as 30-50% of TED patients develop restrictive myopathy affecting the inferior rectus most commonly 1
• Evaluate for corneal exposure from eyelid retraction and proptosis, which threatens vision 1, 4

Treatment Algorithm Based on Thyroid Status

If Hyperthyroid (Graves' Disease Confirmed)

First-Line Medical Management

• Initiate methimazole as the preferred antithyroid agent for most patients, as recommended by the American Association of Clinical Endocrinologists 2, 6
• Titrate dose to maintain Free T4 in high-normal range using the lowest effective dose 2
• Monitor thyroid function every 4-6 weeks initially, then every 2-3 months once stable 2
• Add beta-blockers (atenolol or propranolol) for symptomatic relief of tachycardia, tremor, and anxiety 2

Critical Medication Considerations

• Switch to propylthiouracil if pregnancy is planned or confirmed in first trimester, as methimazole carries rare risk of congenital malformations during organogenesis 2, 6, 7
• Consider switching back to methimazole for second and third trimesters given propylthiouracil's hepatotoxicity risk 2, 6, 7
• Monitor for agranulocytosis by instructing patients to report sore throat, fever, or general malaise immediately 6, 7
• Avoid radioactive iodine therapy if active or severe orbitopathy is present, as it can worsen TED 2

Management of Thyroid Eye Disease

Mild Disease (77% of cases)

• Prescribe ocular lubricants liberally to combat exposure from eyelid retraction and proptosis 2, 4
• Consider selenium supplementation (may reduce inflammatory symptoms in milder disease) 2
• Counsel on smoking cessation, as smoking significantly increases TED risk and severity 1

Moderate-to-Severe Active Disease (CAS ≥3-5)

• Teprotumumab (IGF-1R inhibitor) is highly effective for reducing proptosis and CAS in active TED 1, 2, 4
• However, counsel about hearing loss risk (occurs in 30% of patients) and perform baseline audiometry before treatment 1, 4
• Intravenous methylprednisolone remains treatment of choice in many settings due to teprotumumab's cost, side effects, and high relapse rate 4, 5
• Tocilizumab (IL-6 receptor blocker) is effective for steroid-resistant cases 4

Sight-Threatening Disease (1% of cases)

• Urgent orbital decompression is required for compressive optic neuropathy or severe corneal exposure threatening vision 1, 5
• High-dose intravenous methylprednisolone should be initiated immediately 5
• Consider early tarsorrhaphy for severe corneal exposure 5

Surgical Sequencing for Inactive Disease

• Perform orbital decompression first if indicated 1, 2
• Delay strabismus surgery until after decompression, as decompression increases strabismus risk 1
• Eyelid surgery is performed last to address persistent retraction 1

Critical Pitfalls to Avoid

• Do not miss the transition from hyperthyroidism to hypothyroidism, which commonly occurs with thyroiditis—monitor thyroid function closely every 2-3 weeks after diagnosis 2
• Never use radioactive iodine in pregnant/breastfeeding women or those with active/severe orbitopathy 2
• Do not delay ophthalmology referral when physical examination reveals ophthalmopathy or thyroid bruit, as these findings are diagnostic of Graves' disease 2
• Assess for pre-existing hearing loss before teprotumumab and counsel patients about permanent hearing risk 1
• Monitor prothrombin time before surgical procedures in patients on antithyroid drugs, as both methimazole and propylthiouracil can cause hypoprothrombinemia 6, 7

Risk Stratification

• Female patients (8:1 female:male ratio) in their 40s-50s are highest risk for TED 1
• Smoking, diabetes, hypercholesterolemia, and high anti-thyroid antibody titers significantly increase TED risk and severity 1, 4
• Diseases causing reduced oxygen saturation (emphysema) and vitamin D deficiency are additional risk factors 1