Description

• Graves disease (GD): the most common form; diffuse goiter and thyrotoxicosis are common characteristics. Infiltrative orbitopathy is seen in up to 50% of patients. Infiltrative dermopathy is rare (1). Autoantibodies are directed at the thyroid-stimulating hormone (TSH) receptors.
• Toxic multinodular goiter (TMNG): second most common; most common cause of hyperthyroidism in patients age >65 years; patients >40 years, insidious onset, frequent in iodine-deficient areas
• Toxic adenoma (Plummer disease): younger patients, autonomously functioning nodules
• Iodine-induced hyperthyroidism
• Thyroiditis: transient autoimmune process:
  • Subacute thyroiditis/de Quervain: granulomatous giant cell thyroiditis, benign course; viral infections have been involved.
  • Postpartum thyroiditis
  • Drug-induced thyroiditis: amiodarone, interferon-α, interleukin-2, lithium
  • Miscellaneous: thyrotoxicosis factitia, TSH-secreting pituitary tumors, and functioning trophoblastic tumors (2)[B]
• Subclinical hyperthyroidism: suppressed TSH with normal thyroxine (T₄). There are two grades based on level of TSH. Grade 1 reflects a mild suppression of TSH in the range of (0.1–0.39 mU/L), and grade 2 reflecting a greater suppression with TSH <0.1 mU/L.
• Thyroid storm: rare hyperthyroidism; fever, tachycardia, gastrointestinal (GI) symptoms, CNS dysfunction (e.g., coma); up to 50% mortality

Geriatric Considerations

• Characteristic symptoms and signs may be absent.
• Atrial fibrillation is common when TSH <0.1 mIU/L (3)[A].

Pediatric Considerations

• Neonates and children are treated with antithyroid medications for 12 to 24 months.
• Radioactive iodine treatment is controversial in patients <15 to 18 years.

Pregnancy Considerations
Propylthiouracil is currently the drug of choice during 1st trimester of pregnancy, and methimazole is preferred in the 2nd and 3rd trimester (4)[A]. Treat with lowest effective dose. Avoid treatment-induced hypothyroidism. Radioiodine therapy is contraindicated.

Epidemiology

• 1.3% of population
• Predominant sex: female > male (7 to 10:1)
• Predominant age: autoimmune thyroid disease (GD) in 2nd and 3rd decades; TMNG more common in patients >40 years

Prevalence
The prevalence of hyperthyroidism is 1.3% and can increase in older women to 4–5%.

Etiology and Pathophysiology

• GD: autoimmune disease
• TMNG: 60% TSH receptor gene abnormality; 40% unknown
• Toxic adenoma: point mutation in TSH receptor gene with increased hormone production
• Thyroiditis:
  • Hashitoxicosis: autoimmune destruction of the thyroid; antimicrosomal antibodies present
  • Subacute/de Quervain thyroiditis: granulomatous reaction; genetic predisposition in specific human leukocyte antigens; viruses, such as coxsackievirus, adenovirus, echovirus, and influenza virus, have been implicated; self-limited course, 6 to 12 months
  • Suppurative: infectious
  • Drug-induced thyroiditis: Amiodarone produces an autoimmune reaction and a destructive process. Lithium, interferon-α, and interleukin-2 cause an autoimmune thyroiditis.
  • Postpartum thyroiditis: autoimmune thyroiditis that lasts up to 8 weeks, and in 60% of patients, hypothyroidism manifests in the future

Genetics
Concordance rate for GD among monozygotic twins is 35%.

Risk Factors

• Positive family history, especially in maternal relatives
• Other autoimmune disorders
• Iodide repletion after iodide deprivation, especially in TMNG

Commonly Associated Conditions

• Autoimmune diseases
• Down syndrome
• Iodine deficiency