Graves'%20disease Management

• A life-threatening exacerbation of hyperthyroidism
• Usually preceded with acute illness (eg infection, trauma, stroke), abrupt cessation of antithyroid drugs, radioactive iodine treatment, or surgery

• Fever
• Seizures
• Mental confusion
• Coma
• Vomiting
• Diarrhea
• Jaundice
• Tachycardia

• Treat underlying cause
• Close monitoring and supportive care
  • Cooling, intravenous (IV) fluids

• Important to reduce thyroid hormone synthesis
  • Large doses of Propylthiouracil (PTU)
    • High doses of Methimazole may be used as alternative in patients with contraindications to Propylthiouracil
  • 1 hour after first dose of PTU administer inorganic iodide
    • Inorganic iodide is administered to rapidly reduce T₄ levels by preventing iodide oxidation and organification, and release of thyroid hormone
  • Beta-blocker to reduce adrenergic effects eg tachycardia
    • Cardioselective calcium channel antagonists (eg Diltiazem) may be used as alternative to control heart rate in patients with contraindications to beta-blockers
  • Glucocorticoids may be given
    • Prevent thyroid hormone synthesis and peripheral conversion of T₄ to T₃
  • Bile sequestrants (eg Cholestyramine) may be considered in severe cases to reduce enterohepatic recycling of thyroid hormones
  • Treatment of intercurrent illness or precipitating event; antibiotics may be required if infection is present

• Avoid common precipitants
• Avoid abrupt discontinuation of antithyroid drugs
• Render patient euthyroid prior to surgery

Non-pharmacological therapy

• Maintain euthyroid state
• Smoking cessation
  • Smoking increases risk for Graves' orbitopathy
• Avoid: Bright light, dust
• Sleep with head elevated
• Apply artificial tears and simple eye ointment at night

• Glucocorticoid coverage in patients treated with radioactive Iodine (RAI) and with risk of orbitopathy deterioration if without contraindications
• Trial with Selenium for 6 months was shown to improve soft-tissue swelling but needs further studies

Moderate-Severe Disease

• Increasing diplopia, inflamed eyes, mild corneal irritation

Pharmacological therapy

•  Glucocorticoids
  • Oral Prednisone or pulse intravenous (IV) Methylprednisolone
  • First-line therapy for moderate-severe Graves' orbitopathy
  • IV steroid is more effective and better tolerated therefore preferred over oral steroid
• Rituximab
  • Treatment option for patients intolerant or unresponsive to glucocorticoids
• Teprotumumab
  • An insulin-like growth factor 1 (IGF-1) receptor inhibitor which has been approved by the US FDA for Graves’ orbitopathy and may be used as an alternative in patients unresponsive to glucocorticoids 
• Cyclosporine
  • Studies have shown that combination with glucocorticosteroids was more effective than either therapy alone

Surgery

•  Surgical decompression of orbits

 Radiotherapy

• External orbital radiation
  • Treatment option for patients with contraindications or intolerant or unresponsive to glucocortocoids

• Diplopia, optic neuropathy, or exposure keratitis

Pharmacological Therapy

• Glucocorticoids
  • IV Dexamethasone or Methylprednisolone
  • First-line treatment for sight-threatening Graves' orbitopathy

• Surgical decompression of orbits

• Follow up within 1-2 months after therapy with assessment of free thyroxine  (FT₄), total triiodothyronine (T₃) and thyroid stimulating hormone (TSH)

• Instructions on radiation safety precautions should be given immediately following treatment

• Transient
  • Usually occurs between 2-6 months of therapy and lasts for 1-4 months
  • May choose not to treat
• Permanent
  • Treat with Levothyroxine

• May occur with radioactive Iodine therapy
• Often transient
• May be prevented with the administration of Prednisolone

• Every 4-6 weeks for 6 months or until the patient is hypothyroid and condition has stabilized on thyroid replacement therapy
• Then annually once euthyroidism is achieved or when patient experiences symptoms of hypothyroidism or hyperthyroidism

• Every 4-6 weeks until stable on maintenance thionamide therapy then every 3-6 months thereafter 
• Serum TSH, free T₄ and total T₃ are measured initially every 2-3 months after stopping treatment to check for recurrence; if thyroid function tests remain normal for 6 months, monitoring is tapered to 4-6 month intervals for the next 6 months and then every 6-12 months thereafter  
  • Serum TSH testing is done annually when patient remains euthyroid for 1 year

Surgical Therapy
Hypothyroid

• Patients may become hypothyroid especially with total thyroidectomy
• Treat with Levothyroxine

• Serum TSH every 6-8 weeks then annually once normal or if clinically indicated