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 also be produced from another source.
  • In general, patients with thyrotoxicosis have hyperthyroidism. However, this is not always the case. Patients could suffer from thyrotoxicosis subacute thyroiditis, exogenous thyrotoxicosis, and radiation-induced thyroiditis.
  • Also, medications (such as amiodarone and interferon-α) have cytotoxic effects on thyroid cells resulting in thyrotoxicosis from preformed thyroid hormones.

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); may be associated with osteoporosis and atrial fibrillation
  • Thyroid storm: rare hyperthyroidism; fever, tachycardia, gastrointestinal (GI) symptoms, central nervous system 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

Incidence
  • Female: 1/1,000
  • Male: 1/3,000

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
  • Female
  • Other autoimmune disorders
  • Iodide repletion after iodide deprivation, especially in TMNG

Commonly Associated Conditions

  • Autoimmune diseases
  • Down syndrome
  • Iodine deficiency

-- To view the remaining sections of this topic, please or --

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 also be produced from another source.
  • In general, patients with thyrotoxicosis have hyperthyroidism. However, this is not always the case. Patients could suffer from thyrotoxicosis subacute thyroiditis, exogenous thyrotoxicosis, and radiation-induced thyroiditis.
  • Also, medications (such as amiodarone and interferon-α) have cytotoxic effects on thyroid cells resulting in thyrotoxicosis from preformed thyroid hormones.

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); may be associated with osteoporosis and atrial fibrillation
  • Thyroid storm: rare hyperthyroidism; fever, tachycardia, gastrointestinal (GI) symptoms, central nervous system 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

Incidence
  • Female: 1/1,000
  • Male: 1/3,000

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
  • Female
  • Other autoimmune disorders
  • Iodide repletion after iodide deprivation, especially in TMNG

Commonly Associated Conditions

  • Autoimmune diseases
  • Down syndrome
  • Iodine deficiency

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