graves'%20disease
GRAVES' DISEASE
Graves' disease is an autoimmune disorder that results into overproduction of thyroid hormones.
Thyrotoxicosis signs and symptoms include hyperactivity, irritability, insomnia, dysphoria, sweating, heat intolerance, palpitations, weakness, fatigue, weight loss despite increased appetite, diarrhea, steatorrhea polyuria, decreased libido, tachycardia, tremor, goiter, alopecia, gynecomastia, eyelid lag or retraction and rarely periodic paralysis.
Clinical features in thyrotoxic patient that suggests Graves's disease are ophthalmopathy, thyroid dermopathy, thyroid acropachy, diffuse goiter, antibodies to thyroid peroxidase or thyroglobulin and thyroid radionuclide scan demonstrating a diffuse goiter.

Graves'%20disease Management

Thyrotoxic Crisis

  • 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
Signs and Symptoms
  • Fever
  • Seizures
  • Mental confusion
  • Coma
  • Vomiting
  • Diarrhea
  • Jaundice
  • Tachycardia
Non-pharmacological Therapy
  • Treat underlying cause
  • Close monitoring and supportive care
    • Cooling, intravenous (IV) fluids
Pharmacological Therapy
  • 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
Prevention
  • Avoid common precipitants
  • Avoid abrupt discontinuation of antithyroid drugs
  • Render patient euthyroid prior to surgery

Graves' Orbitopathy

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
Mild Disease
Pharmacological Therapy
  • 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
Sight-threatening
  • Diplopia, optic neuropathy, or exposure keratitis

Pharmacological Therapy

  • Glucocorticoids
    • IV Dexamethasone or Methylprednisolone
    • First-line treatment for sight-threatening Graves' orbitopathy
Surgery
  • Surgical decompression of orbits



 

Follow Up

Radioactive Iodine Therapy
  • Follow up within 1-2 months after therapy with assessment of free thyroxine  (FT4), total triiodothyronine (T3) and thyroid stimulating hormone (TSH)
Patient Education
  • Instructions on radiation safety precautions should be given immediately following treatment
Hypothyroidism (Permanent or Transient)
  • Transient
    • Usually occurs between 2-6 months of therapy and lasts for 1-4 months
    • May choose not to treat
  • Permanent
    • Treat with Levothyroxine
Worsening of Eye Disease
  • May occur with radioactive Iodine therapy
  • Often transient
  • May be prevented with the administration of Prednisolone
Follow Up Exams
  • 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
Pharmacological therapy
Follow Up Exams
  • 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
Follow Up Exams
  • Serum TSH every 6-8 weeks then annually once normal or if clinically indicated
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