Hyperthyroidism

Basics

  • Hyperthyroidism or thyrotoxicosis is due to thyroid hormone excess. The former describes excess from the thyroid gland, whereas the latter can also be produced from another source.
  • In general, patients with thyrotoxicosis have hyperthyroidism. However, patients could suffer from thyrotoxicosis subacute thyroiditis, exogenous thyrotoxicosis, and radiation-induced thyroiditis.

Description

  • Graves disease (GD) is the most common cause with autoantibodies directed at the thyroid-stimulating hormone (TSH) receptors.
  • Toxic multinodular goiter (TMNG) is the most common cause of hyperthyroidism in patients >65 years of age; often an insidious onset, frequent in iodine-deficient areas
  • Toxic adenoma (Plummer disease) is seen in younger patients—autonomously functioning nodules.
  • TSH-producing adenoma, not to be confused with a resistance to thyroid hormone
  • Iodine-induced hyperthyroidism
  • 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
  • Subclinical hyperthyroidism: suppressed TSH with normal thyroxine (T4)
    • Grade 1 reflects a mild suppression of TSH in the range of 0.10 to 0.39 mU/L.
    • Grade 2 reflects a greater suppression with TSH <0.1 mU/L.
  • Thyroid storm: 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 (1)[A].

Pediatric Considerations

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

Pregnancy Considerations
Propylthiouracil (PTU) is currently the drug of choice during 1st trimester of pregnancy, and methimazole is preferred in the 2nd and 3rd trimesters (2)[A]. Treat with lowest effective dose because PTU can cross the placenta and put the fetus at risk for goiter. 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 is more common in patients aged >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
  • Hashitoxicosis: autoimmune destruction of the thyroid; antimicrosomal antibodies present
  • Subacute/de Quervain thyroiditis: Granulomatous reaction viruses, such as coxsackievirus, adenovirus, echovirus, and influenza virus, have been implicated.
  • Drug-induced thyroiditis: amiodarone, lithium, interferon-α, and interleukin-2
  • 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

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