INTRODUCTION
Graves disease is caused by autoantibodies that bind to the thyrotropin receptor (TSHR-Ab), stimulating growth of the thyroid and overproduction of thyroid hormone. It is by far the most common cause of hyperthyroidism in children. Clinical manifestations of Graves disease include diffuse goiter and symptoms and signs resulting from hyperthyroidism. Graves disease is often associated with ophthalmopathy, which is not found in other etiologies of hyperthyroidism. In contrast, "stare" and lid-lag (eye findings resulting from sympathetic overactivity) may be present in any form of hyperthyroidism. In children, hyperthyroidism also tends to have effects on growth and development.
The clinical presentation and laboratory evaluation of children with hyperthyroidism are discussed here. Treatment of hyperthyroidism is discussed separately. Hyperthyroidism presenting during the neonatal period also is discussed separately. (See "Treatment and prognosis of Graves disease in children and adolescents" and "Evaluation and management of neonatal Graves disease".)
TERMINOLOGY
Hyperthyroidism versus thyrotoxicosis — The terms "hyperthyroidism" and "thyrotoxicosis" are often used interchangeably. However, strictly speaking, hyperthyroidism refers to overproduction of thyroid hormone by the thyroid gland, while thyrotoxicosis refers to the clinical and biochemical manifestations of excess thyroid hormones. Most cases of thyrotoxicosis are caused by hyperthyroidism, particularly in children. However, thyrotoxicosis occasionally is caused by release of preformed stored thyroid hormone, as in some cases of destructive thyroiditis.
EPIDEMIOLOGY
Hyperthyroidism occurs in approximately 1 per 5000 children and adolescents, and Graves disease accounts for the vast majority of these cases. Other causes are outlined in the table (table 1) [1]. In a national population-based study of thyrotoxicosis from the United Kingdom and Ireland in 2004, the annual incidence was 0.9 per 100,000 children <15 years of age, with Graves disease accounting for 96 percent of cases [2]. A nationwide study from Denmark reported an incidence of 0.79 per 100,000 in children <15 years of age in the time period of 1982 to 1988, with a doubling to 1.58 per 100,000 in the years 1998 to 2012 [3].
The incidence of Graves disease rises sharply during puberty, so that approximately 80 percent of pediatric cases occur after 11 years of age [1-4]. During adolescence, a strong female predominance develops, at a ratio of approximately 5:1 [2-4]. The ratio is considerably lower among younger children, suggesting that estrogen secretion in some way affects the autoimmune predisposition to Graves disease. A report using data from the United States National Health and Nutritional Examination Surveys analyzing adolescents and young adults found that thyrotoxicosis was more common in non-Hispanic Black Americans than Mexican Americans, in whom it was more common than non-Hispanic White Americans [5].
