• Clinical science

Graves disease

Abstract

Graves disease is the most common cause of hyperthyroidism and often affects women. It is an autoimmune condition that is associated with circulating TSH receptor autoantibodies leading to overstimulation of the thyroid with excess thyroid hormone production. The classic clinical triad of Graves disease involves a diffuse vascular goiter, ophthalmopathy, and pretibial myxedema, although not all features may be present in a patient. The clinical diagnosis of Graves disease is confirmed via assessment of TSH and T3/T4 levels as well as through detection of thyroid antibodies (TRAbs, anti-TPO, anti-Tg). In addition, a diffuse uptake of 123I may be seen on thyroid scintigraphy. Treatment includes β-blockers to quickly alleviate symptoms, antithyroid drugs to achieve euthyroid status, and radioiodine ablation or, less commonly, near-total thyroidectomy for definitive control of the disease.

Epidemiology

  • Most common cause of hyperthyroidism in the United States
  • Incidence: ∼ 30 cases per 100,000 people per year
  • Sex: > (8:1)
  • Typical age range: 20–40 years

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[1][2]

Pathophysiology

Clinical features

References:[3][4][5]

Graves dermopathy

  • A rare manifestation of Graves disease, occurring in < 5% of patients
  • Women are more commonly affected than men
  • Often occurs in patients > 50 years of age
  • When present, it occurs about two years after the onset of hyperthyroidism and six months to one year after the onset of Graves ophthalmopathy (GO).
  • Nearly all patients with Graves dermopathy have co-existent GO.
  • Etiology: Thyroid dermopathy is due to the deposition of hyaluronic acid in the dermis and subcutaneous tissue.
  • Clinical findings
    • Non-pitting edema and firm plaques on the anterior/lateral aspects of both legs, hence the name pre-tibial myxedema. Occasionally occurs in upper limbs and even the face.
    • Lesions worsen on prolonged standing/surgery/trauma to the lower limbs
    • Elephantiasis Nostras Verrucosa (ENV) is a rare form of pretibial myxedema and is nearly always associated with Graves disease. The legs are massively enlarged, making walking difficult.
    • Thyroid acropachy:
      • Seen in 1% of patients with Graves disease
      • Clubbing of the fingers and the toes
      • Periosteal proliferation of the phalangeal bones
      • Swelling of the soft tissues overlying affected bony structures.
      • When present, acropachy is a marker of severe ophthalmopathy.
  • Differential diagnosis
  • Diagnostics
    • The diagnosis is often clinically obvious
    • Skin biopsy of the affected lesion : GAG deposition in the reticular dermis
    • Other diagnostic tests for Graves disease (see “Diagnostics” below)
  • Therapy
    • Local corticosteroid application
    • Compression stockings are useful as an adjunctive therapy.

Diagnostics

The diagnosis of Graves disease is often apparent on clinical examination and is confirmed through detection of specific thyroid antibodies.

References:[3][6][1][7]

Treatment

References:[8][1]

Graves disease in children

  • Most common cause of hyperthyroidism in children
  • Clinical features
    • Features of hyperthyroidism (See “Symptoms/clinical findings” in hyperthyroidism)
    • Most children develop a goiter, which can be large and cause compressive symptoms (See “Symptoms/clinical findings” in goiter)
    • Younger children often show a growth spurt
    • Graves ophthalmopathy, if present, is often mild. However, lid lag causing apparent proptosis is often seen.
    • Graves dermopathy rarely occurs in children.
  • Therapy
    • Antithyroid drugs
      • Best initial treatment
      • Methimazole is the drug of choice
      • Most children go into remission within 2 years of treatment.
    • Symptom control with β blockers: atenolol, propranolol
    • Radioactive iodine (RAI) ablation
      • In children > 10 years/adolescents without large goiters: Potential first-line treatment option
      • In children who relapse after long-term therapy with antithyroid drugs: as a second-line treatment
      • In children > 5 years: lower dose is recommended
      • Contraindicated in children < 5 years
      • Nearly half the children treated with radioiodine ablation become hypothyroid → thyroid hormone replacement
      • Risk of thyroid cancer is not elevated with therapeutic/diagnostic doses of radioactive iodine.
    • Surgery: Near-total thyroidectomy is indicated in
    • Lifelong monitoring of thyroid function

Graves disease in the elderly

  • Graves disease is the second most common cause of hyperthyroidism in the elderly, after toxic multinodular goiter
  • The classic signs/symptoms of thyrotoxicosis are often absent/minimal in the elderly
  • Treatment of other co-existing diseases may mask the symptoms of hyperthyroidism; e.g., β blockers for hypertension/angina may mask tachycardia and tremors.
  • A high degree of clinical suspicion is required to make the diagnosis.
  • Monosymptomatic hyperthyroidism: Elderly patients may present with only one symptom of hyperthyroidism, myopathy being the most common.
  • Apathetic hyperthyroidism
    • A common presentation of Graves in the elderly
    • Characteristic absence of ophthalmopathy
    • No/small goiter
    • No tremor
    • Neuropsychiatric symptoms: apathy, depression, lethargy
    • Thyroid myopathy: proximal muscle weakness is the predominant symptom and sign
    • Excessive weight loss and cardiac arrhythmias are often present
  • Such features in a previously stable elderly patient in the setting of vague or nonlocalizing symptoms should warrant thyroid evaluation.
  • Diagnostics: The diagnosis of thyrotoxicosis in the elderly is often made during laboratory workup for unexplained weight loss or worsening cardiovascular disease. (See “Diagnostics” section above)
  • Therapy:
    • RAI ablation is the treatment of choice.
    • Antithyroid drugs: to achieve a euthyroid state before RAI ablation. Must be discontinued at least one week before RAI ablation for the ablation to be successful.
    • Surgery: rarely indicated due to increased operative and anesthetic in the elderly.