HYPERTHYROIDISM IN CHILDREN
Hyperthyroidism is less common in children compared to hypothyroidism but is often associated with more severe symptoms. The clinical manifestations of hyperthyroidism in children and adolescents are similar to those seen in adults. Children may have some additional manifestations due to the effect of excessive thyroid hormone on growth and development. Although there are several causes of hyperthyroidism in children (Table 522-1), Graves’ disease is the most common.
TABLE 522-1CAUSES OF HYPERTHYROIDISM IN CHILDREN |Favorite Table|Download (.pdf) TABLE 522-1 CAUSES OF HYPERTHYROIDISM IN CHILDREN
|Graves’ disease |
|Thyroid-stimulating hormone (TSH) hypersecretion (often caused by pituitary tumor) |
|Pituitary resistance |
|Autonomous nodule(s) |
|McCune-Albright syndrome |
|Activating mutation of TSH receptor |
|Iodine-induced hyperthyroidism |
|Thyroid hormone ingestion |
|Maternal Graves’ disease |
|Maternal Hashimoto thyroiditis |
Graves’ disease is a multisystem autoimmune disease involving hyperthyroidism, eye manifestations, and dermopathy. In children, in contrast to adults, the latter manifestations are absent or mild.
The disease occurs in preschool children; rarely, it may begin in infancy. However, the incidence increases sharply as children approach adolescence. Girls are affected 6 to 8 times more often than boys. Graves’ disease, like Hashimoto thyroiditis, has a genetic basis; a high proportion of patients have a family history of goiter, hyperthyroidism, or hypothyroidism. The concordance rate for Graves’ disease in monozygotic twins has been reported as 30% to 60%; in dizygotic twins, it is only 3% to 9%. Family studies have demonstrated a high percentage of circulating antithyroid antibodies in near relatives. Furthermore, certain human leukocyte antigen (HLA) haplotypes, such as HLA B8 and DR3 in whites, and linkage to genetic determinants on the X chromosome and chromosomes 14 and 20 have been reported in affected families.
The hyperthyroidism is due to the production of thyroid-stimulating autoantibody, which, like thyroid-stimulating hormone (TSH), stimulates the TSH receptor. The 3 principal autoantigens in Graves’ disease (the TSH receptor, thyroid peroxidase, and thyroglobulin) have been cloned. Autoantibodies to the TSH receptor have the major pathogenic role in Graves’ disease. The production of thyroid-stimulating antibodies by B lymphocytes is probably a secondary response to a cell-mediated immune reaction requiring involvement of T lymphocytes in a manner similar to that postulated for Hashimoto thyroiditis. Cell cultures of lymphocytes from patients with Graves’ disease produce immunoglobulins only after stimulation with phytohemagglutinin. Because the latter substance stimulates only T cells (which are incapable of secreting immunoglobulins), it may be inferred that both cell-mediated and humoral immune mechanisms are involved in the genesis of the thyrotoxic state. This is supported by more recent studies indicating that thyrocytes can be activated by thyroid-stimulating antibodies plus insulin-like growth factor 1 (IGF-1) to express powerful chemoattractants that stimulate T-cell infiltration independently of the TSH receptor.