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Hypothyroidism: Overview and Risk Factors

Hypothyroidism is a condition in which the thyroid gland fails to secrete sufficient thyroxine (T4) and triiodothyronine (T3). The disease may reflect intrinsic thyroid dysfunction (primary hypothyroidism), or it may result from insufficient stimulation of the thyroid gland by thyroid–stimulating hormone (TSH) due to a malfunction in the hypothalamic–pituitary axis (secondary hypothyroidism).

Clinical manifestations may be subtle and nonspecific, including weakness, fatigue, and weight gain. However, chronic or severe disease can manifest with goiter, dull facial expression, drooping eyelids, hoarse speech, thinning or dry, brittle hair, dry skin, myxedema (swelling of the skin and soft tissues), menstrual disorders, bradycardia, pericardial effusion, constipation, depression, paresthesias, ataxia, and anemia. 

Hypothyroidism affects about 5 million Americans. The most common cause worldwide is iodine deficiency. However, in the United States, where iodized salt is commonly used, most cases are due to autoimmune thyroiditis (Hashimoto’s disease), in which CD8+ lymphocytes and antithyroid antibodies impair the normal functioning of the thyroid gland. Other causes include drugs (lithium, amiodarone), genetic mutations of thyroglobulin and thyroid peroxidase molecules, congenital hypothyroidism, neck surgery, and radiothyroid ablation therapy. Hypothyroidism may also result from hypothalamic or pituitary disorders, such as pituitary tumors, postpartum pituitary necrosis, and head trauma, in which the production or release of TSH is impaired.

Some, but not all, patients with hypothyroidism develop a goiter. The clinical presentation of goiter depends on its size and location and may include cough, dyspnea and wheezing due to tracheal compression, dysphagia due to esophageal compression, hoarseness resulting from laryngeal nerve compression, and Horner’s syndrome if the cervical sympathetic chain is involved.

Myxedema coma is a life–threatening complication manifested by mental status changes, often accompanied by hypotension, hypothermia, hypoventilation, and, though rarely, coma. (Its name is actually a misnomer, because patients typically exhibit neither the nonpitting swelling of the skin referred to as myxedema nor coma.) Precipitants of myxedema coma include infection, myocardial infarction, stroke, trauma (including surgery and burns), hypoglycemia, hyponatremia, hemorrhage, noncompliance with thyroid medications, and various drugs (eg, beta–blockers, sedatives, narcotics, and phenothiazines). 

Risk Factors

    • Gender. The majority of cases occur in women.
    • Age. Risk of hypothyroidism and myxedema coma increases with age.
    • Genetics. Hypothyroidism is associated with several polymorphisms in the genes for human leukocyte antigen (HLA), T–cell antigen receptors, and other immunomodulatory molecules.
    • Obesity is an important risk factor.


    Hypothyroidism: Diagnosis and Treatment >>