Hyperthyroidism
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Basics

Hyperthyroidism or thyrotoxicosis is composed of a spectrum of clinical findings consistent with thyroid hormone excess. The former describes excess from the thyroid gland, whereas the latter can be produced from any other source.

Description

  • Graves disease (GD): The most common form; diffuse goiter and thyrotoxicosis are common characteristics. Infiltrative orbitopathy is seen in 50% of patients. Infiltrative dermopathy is rare. Autoantibodies are directed at the thyrotropin-stimulating hormone (TSH) receptors.
  • Toxic multinodular goiter (TMNG): 2nd most common; a TSH receptor mutation has been found in 60% of patients; patients age >40 years, insidious onset, frequent in iodine-deficient areas
  • Toxic adenoma: 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
  • Subclinical hyperthyroidism: Suppressed TSH with normal thyroxine (T4); may be associated with osteoporosis and atrial fibrillation (1).
  • Thyroid storm: Rare hyperthyroidism; fever, tachycardia, systolic hypertension, 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 mU/L.
Pediatric Considerations
  • Neonates and children are treated with antithyroids for 12–24 months.
  • Radioactive iodine is controversial in patients under the ages of 15–18 years.

Pregnancy Considerations
Propylthiouracil (PTU) is currently the drug of choice during pregnancy. Treat with lowest effective dose. Avoid treatment-induced hypothyroidism. Radioiodine therapy is contraindicated.

Epidemiology

  • 1.3% of population
  • Predominant sex: Female > Male (7–10:1).
  • Predominant age: Autoimmune thyroid disease in 2nd and 3rd decades. TMNG presents in patients >40 years. GD is seen between 40 and 60 years of age.
Incidence
  • Female 1/1,000
  • Male: 1/3,000

Risk Factors

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

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

Etiology

  • 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 HLAs; viruses, such as coxsackievirus, adenovirus, echovirus, and influenza virus, have been implicated; self-limited course, 6–12 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.

Commonly Associated Conditions

  • Autoimmune diseases
  • Down syndrome
  • Iodine deficiency

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