Graves disease is the most common cause of hyperthyroidism in pediatric patients. It is an immune-mediated disorder that results from the production of thyroid-stimulating immunoglobulins (TSI) by stimulated B lymphocytes. These immunoglobulins bind to the thyroid-stimulating hormone (TSH) receptor to mimic the action of TSH and stimulate thyroid growth and thyroid hormone overproduction. (See Etiology.)
Signs and symptoms of thyrotoxic Graves disease include an enlarged thyroid, rapid heart rate, widened pulse pressure, a hyperthyroid stare (infrequent blinking) or frank exophthalmos, tremor, sweating, palpitations, smooth moist skin, frequent bowel movements or diarrhea, sleeplessness, attention problems in school, irritability, and weight loss. (See Clinical.)
Diagnosis requires identification of suppressed TSH (thyrotropin) levels and elevated levels of free thyroxine (FT 4 ) and/or triiodothyronine (T 3 ). Measurement of TSI is of interest but is not required for therapeutic evaluation. Treatment is directed at alleviating symptoms and reducing thyroid hormone production. Symptoms may be improved by treatment with beta-blocking drugs. Reduction of thyroid hormone is accomplished by use of drug therapy, surgical subtotal thyroidectomy, or treatment with radioactive iodine (RAI). Because circulating TSI can cross the placenta, infants born to women with a history of Graves disease may have transient neonatal Graves thyrotoxicosis and require treatment. (See Workup, Treatment, and Medications.)
Although Perry was first to report hyperthyroidism in English, the classic description, in 1835, by Graves became most widely accepted. Europeans often prefer to recognize the description by Basedow. Examples of patients with thyrotoxicosis are shown below.
A 16-year-old girl with thyrotoxicosis for 3 years is shown. Note her thyrotoxic stare (infrequent blinking with exophthalmos) and enlarged thyroid gland (goiter).
Neonate with thyrotoxicosis secondary to transplacental passage of maternal thyroid-stimulating immunoglobulins (TSI). The baby has a noteworthy stare. Upon examination, a small goiter and a rapid heart rate could be appreciated.
The most common association with childhood Graves disease is a history of other family members with thyroid disease. On the other hand, concordance for Graves disease in identical twins is only 30-50%, indicating that genetic and environmental factors play a role in this disease. (See Etiology.)
Graves disease is potentially life threatening. The most severe manifestation of Graves disease is thyroid storm, which carries a mortality risk approaching 100% in untreated adults. Series conducted with newer treatments, including beta-adrenergic blocking agents, show a reduced risk of death near 20%. This is such a rare disorder in children that no comparable figures are available. (See Prognosis, Treatment, and Medications.)
Even children and adolescents with less severe manifestations of Graves disease can display long-term consequences of this disorder, including problems with schooling and chronic loss of bone mineral.
Instruct patients treated with antithyroid drugs as to possible adverse effects and the need for close follow-up.
Patients treated with surgery and RAI must understand the rationale for the development of hypothyroidism and the need for close follow-up.