Graves’ Disease

Graves’ disease is an autoimmune disease that affects the thyroid and is the most common cause of hyperthyroidism. Robert James Graves, an Irish physician and surgeon, described the condition in 1835 in the London Medical and Surgical Journal.

Pathogenesis

• Autoimmune disorder 
• B lymphocytes product TRAb which bind and activate TSH receptor on thyroid cells
• Excessive T3 and T4 production 

Presentation

• Hyperthyroidism
  • Tachycardia
  • Hypertension
  • Palpitations
  • Weight loss
  • Heat intolerance
  • Diaphoresis
  • Anxiety
  • Fatigue
  • Nausea
  • Vomiting
  • Diarrhea 
• Graves’ specific
  • Exophthalmos →  abnormal protrusion of one or both eyes due to increased volume of contents in the orbit (fat, muscle, etc.) that forces the eyeball to move forward
  • Pretibial myxedema → discolored thickening of the skin
  • Goiter is smooth and nontender

Workup

• First step:
  • Low TSH (highest sensitivity and specificity)
  • Elevated T3 or T4
• Next step:
  • Thyroid receptor antibodies (TRAb) → anti-TSH receptor IgG Ab
  • Thyroid uptake scan → diffuse uptake
  • Ultrasound → diffuse enlargement and increased vascularity; if nodules >1 cm are present a biopsy with FNA should be considered to rule out malignancy 

Treatment

• Immediate control of symptomatic thyrotoxicosis with Beta-blocker
  • Decrease sympathetic hyperactivity
  • Decrease peripheral conversion ot T4 to T3
• Initiate antithyroid drugs
  • Thioamides: Methimazole or Propylthiouracil
    • Methimazole
      • MOA: inhibit TPO
      • Pregnancy is contraindication (due to cretinism risk), but it may be safe in second or third trimester
      • Side effects:agranulocytosis
    • Propylthiouracil
      • MOA: inhibit TPO and peripheral conversion of T4 to T3
      • Safe in pregnancy
      • Side effects: hepatotoxicity, agranulocytosis
    • Note: exophthalmos is resistant to thioamide treatment 
  • Definitive treatment → required by majority of patients
    • Radioactive iodine ablation (RAI)
      • Contraindications
        • Thyroid malignancy
        • Pregnancy
        • Lactation
        • Children <5 years old
        • Moderate-severe exophthalmos (may worsen)
      • Side effects: transient hyperthyroidism exacerbation, neck pain, sialadenitis 
    • Surgery → total thyroidectomy
      • Patients should be made euthyroid prior to surgical intervention
      • Indications
        • Suspicious nodule
        • Noncompliant with medication
        • Pregnancy in <6 months
        • Compressive goiter
        • Parathyroidectomy
        • Low RAI uptake
        • Medications or RAI failure
        • Moderate-severe orbitopathy
      • Adjuncts
        • Calcium
        • Iodine solution (Lugol’s or saturated solution of potassium iodide)
      • Conversion to thyroid lobectomy if concern for traction injury to recurrent laryngeal nerve