What are the symptoms and treatment options for Graves' disease?

Graves' Disease: Symptoms and Treatment Options

Methimazole is the preferred first-line treatment for most patients with Graves' disease, with a standard protocol of 12-18 months of therapy and monitoring every 4-6 weeks initially, then every 2-3 months once stable. 1

Clinical Presentation and Diagnosis

• Graves' disease is characterized by hyperthyroidism, diffuse goiter, and in approximately 50% of patients, ophthalmopathy 2

• Common symptoms include:

  • Tachycardia, tremor, anxiety, and other manifestations of thyrotoxicosis 3
  • Proptosis (bulging eyes) and other ocular symptoms in those with ophthalmopathy 4
  • Rarely, infiltrative dermopathy and acropachy (clubbing of fingers and toes) 2

• Diagnosis is confirmed by:

  • Low TSH, elevated Free T4, and positive TSH receptor antibody (TRAb) testing 1, 5
  • Thyroid ultrasound typically shows a hypervascular and hypoechoic thyroid gland 5
  • Presence of ophthalmopathy makes the diagnosis almost unmistakable 2

Treatment Options

First-Line Treatment: Antithyroid Medications

• Methimazole is the preferred first-line agent for most patients 1, 6

  • Standard protocol: 12-18 months of therapy
  • Monitoring: Every 4-6 weeks initially, then every 2-3 months once stable
  • Goal: Maintain Free T4 in high-normal range using lowest possible dose

• Propylthiouracil is indicated for patients who are:

  • Intolerant to methimazole 7
  • Women planning pregnancy or in first trimester of pregnancy 1, 5

Adjunctive Therapy

• Beta-blockers are recommended for symptomatic relief of tachycardia, tremor, and anxiety 1
• Ocular lubricants are almost always needed for patients with ophthalmopathy to combat exposure related to eyelid retraction and proptosis 4
• Selenium supplementation may reduce inflammatory symptoms in patients with milder thyroid eye disease 4

Second-Line Treatment Options

• Radioactive iodine (RAI) therapy:

  • Often preferred in the US for adults with Graves' disease 3
  • Contraindicated in pregnancy and breastfeeding 1
  • Contraindicated in patients with active/severe orbitopathy 5
  • Steroid prophylaxis is warranted in patients with mild/active orbitopathy receiving RAI 5

• Thyroidectomy:

  • Recommended for patients who don't respond to antithyroid medications, have very large goiters, or have contraindications to both antithyroid drugs and RAI 1
  • Should be performed by an experienced high-volume thyroid surgeon 1
  • Offers the highest cure rate in the shortest period of time 8

Management of Special Populations

• Pregnancy:

  • Switch from methimazole to propylthiouracil during first trimester 1, 5
  • Return to methimazole after first trimester 1
  • Goal: Maintain maternal Free T4 in high-normal range using lowest possible dose 1

• Thyroid eye disease:

  • Teprotumumab (IGF-IR inhibitor) reduces proptosis and clinical activity score in many patients with active disease 4
  • Consider orbital decompression, high-dose steroids, or radiation treatment for severe proptosis or optic neuropathy 4
  • If orbital decompression is indicated, strabismus repair should be delayed until after the decompression 4

Monitoring and Follow-up

• Monitor thyroid function every 2-3 weeks initially, then every 4-6 weeks once stable 1
• Watch for common side effects of antithyroid drugs 1
• For patients with ophthalmopathy:
  • Monitor for optic neuropathy with acuity, color vision, visual fields, pupillary exam, and fundus exam 4
  • Consider ocular coherence tomography and Humphrey visual fields to screen for or monitor possible associated compressive optic neuropathy 4

Common Pitfalls to Avoid

• Failing to recognize transition from hyperthyroidism to hypothyroidism 1
• Using radioactive iodine in pregnant or breastfeeding women 1
• Overlooking ophthalmopathy or thyroid bruit, which are diagnostic of Graves' disease 1
• Delaying treatment of severe ophthalmopathy, which can lead to permanent vision loss 4