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- 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 another source.
- In general, patients with thyrotoxicosis have hyperthyroidism. However, this is not always the case. Patients could suffer from thyrotoxicosis not due to a prolonged elevation in thyroid hormone synthesis. Examples include 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.
- 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. 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 (1)[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, CNS dysfunction (e.g., coma); up to 50% mortality
- Neonates and children are treated with antithyroids for 12 to 24 months.
- Radioactive iodine treatment is controversial in patients <15 to 18 years.
Propylthiouracil is currently the drug of choice during 1st trimester of pregnancy, and methimazole is preferred in the 2nd and 3rd trimester (3)[A]. Treat with lowest effective dose. Avoid treatment-induced hypothyroidism. Radioiodine therapy is contraindicated.
- 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
- Female: 1/1,000
- Male: 1/3,000
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; 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
Concordance rate for GD among monozygotic twins is 35%.
- 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