Grave's Disease

Aka: Grave's Disease, Basedows Disease, Exophthalmic Goiter, Graves Disease, Graves Dermopathy

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II. Epidemiology

  1. Most common cause of Thyrotoxicosis in the United States (up to 60-80% of cases)
  2. Prevalence: 20 to 50 in 100,000
  3. Gender: More common in women

III. Pathophysiology

  1. Autoimmune disorder
  2. Thyroid stimulating antibodies bind TSH receptors, resulting in Thyroid Hormone synthesis and release
  3. Associated with Thyroid Gland hyperplasia and Goiter

IV. Risk Factors

  1. Female gender (RR 4 compared with males)
  2. Autoimmune Disorder
  3. Family History of Graves Disease (or other autoimmune disorder)
  4. Tobacco Abuse
  5. Iodine exposure

V. Findings

  1. See Hyperthyroidism
  2. Older patients may present less specifically (e.g. Fatigue, weight loss, Atrial Fibrillation)

VI. Signs: Specific to Grave's Disease

  1. See Hyperthyroidism
  2. Diffuse, smooth Goiter
    1. Palpated thrill or audible bruit over Thyroid
  3. Infiltrative ophthalmopathy or orbitopathy (Thyroid Eye Disease)
    1. Ophthalmoplegia
    2. Proptosis (Exophthalmos) in 25-50% of cases
    3. Periorbital swelling
  4. Dermopathy
    1. Pretibial Myxedema (Thyroid dermopathy, 1.5% of cases)
      1. Swelling over the tibia
      2. Peau d' orange skin changes
    2. Thyroid Acropachy
      1. Hand soft tissue swelling and Digital Clubbing
    3. Skin Pigment Changes
      1. Patchy Hyperpigmentation or vitilgo

VII. Differential Diagnosis

  1. See Hyperthyroidism

VIII. Labs

  1. See Hyperthyroidism
  2. Thyroid Stimulating Immunoglobulin (TSH Receptor Antibody)
    1. Test Sensitivity: 97%
    2. Test Specificity: >=98%
    3. Linked with ophthalmopathy
    4. May be used to monitor effects of treatment
    5. Usually not needed for diagnosis
      1. However, may be used in lieu of Thyroid uptake scan in Grave's Disease diagnosis
  3. Antithyroid Peroxidase Antibody negative
    1. Contrast with positive in Hashimoto's Thyroiditis

IX. Imaging

  1. Thyroid uptake and scan (first-line study)
    1. Diffusely high Radioactive Iodine uptake
  2. Thyroid Ultrasound with doppler (if performed)
    1. Thyroid hypervascularity with increased flow

X. Management

  1. See Hyperthyroidism Management
  2. Referral to ophthalmology for ocular involvement
  3. Antithyroid Medications (Thionamides)
    1. Indications
      1. Grave's Disease without Goiter
        1. Thionamides are first-line treatment
        2. Result in euthyroid state within 18 months in up to 50%
    2. Medications
      1. Methimazole 15-30 mg per day (up to 120 mg)
      2. Propylthiouracil (PTU) 100-200 mg orally every 8 hours
        1. Indicated in pregnancy first trimester
    3. Monitoring
      1. See Antithyroid Medications
      2. Thyroid function
        1. First: T4 Free, Total T3 every 4-6 weeks until euthyroid
        2. Next: TSH, T4 Free every 3-6 months
      3. Adverse Effects
        1. Agranulocytosis (CBC)
        2. Hepatotoxicity (LFT)
    4. Efficacy: Predictors of remission with Thionamides
      1. TSH Receptor Antibody negative
      2. Non-smoker
      3. Female Gender
  4. Radioactive Iodine (RAI)
    1. Indications
      1. Failed remission with Thionamides after 12-24 months
      2. High dose Thionamides required or adverse effects
      3. Toxic Multinodular Goiter
    2. Contraindications
      1. Pregnancy
      2. Current Lactation or Lactation in the last 3 months
    3. Efficacy
      1. Effective in Graves Disease in >90% of patients
    4. Monitoring
      1. Thyroid Function Tests every 4-6 weeks
      2. Anticipate Hypothyroidism in up to 86% of Graves Disease patients treated with RAI
    5. Precautions
      1. RAI exacerbates Thyroid Eye Disease, esp. in smokers (pretreat with Corticosteroids)
  5. Thyroidectomy
    1. See Thyroidectomy for indications

XI. References

  1. Humphrey (2024) Am Fam Physician 109(6): 567-8 [PubMed]
  2. Kravets (2016) Am Fam Physician 93(5): 363-70 [PubMed]
  3. Mounsey (2025) Am Fam Physician 112(2): 146-52 [PubMed]

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