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Graves disease is a multisystem autoimmune disease involving
hyperthyroidism, eye manifestations, and dermopathy.1-12In
children, in contrast to adults, the latter manifestation are absent
or mild.
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The disease occurs in preschool children; rarely, it may begin
in infancy. However, the incidence increases sharply as children
approach adolescence. Girls are affected six to eight times more
often than boys. Graves disease, like Hashimoto thyroiditis, has
a genetic basis; a high proportion of patients have a family history
positive for goiter, hyperthyroidism, or hypothyroidism. It is believed
that both Graves disease and Hashimoto thyroiditis arise randomly
in a genetically predisposed population. 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 disclosed a high percentage of circulating antithyroid
antibodies in near relatives. Furthermore, certain HLA haplotypes,
such as HLA B8 and Dr3 in Caucasians, and linkage to genetic determinants
on the X chromosome and chromosomes 14 and 20 have been reported
in affected families.
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The hyperthyroidism is due to the production of thyroid-stimulating
autoantibody, which, like thyroid-stimulating hormone (TSH), stimulates the
TSH receptor. The three principal autoantigens in Graves disease
(the TSH receptor, thyroid peroxidase, and thyroglobulin) have been cloned.
The TSH receptor autoantibodies have the major pathogenetic 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 TSA + insulinlike growth factor 1 (IGF-1)
to express powerful T-cell chemoattractants that stimulate T-cell
infiltration independently of the TSH receptor.
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The onset of thyrotoxicosis is usually insidious, with a period
of increasing nervousness, palpitation, increased appetite, and
muscle weakness.8-11 Marked weight loss occurs
in some patients, usually in association with a voracious appetite.
Occasionally, children and especially adolescents show a weight
increase with the onset of the disease. Except for exophthalmos
and other eye signs, the symptoms of thyrotoxicosis are nonspecific
and, for prolonged periods, may be mistaken for some other condition.
Behavioral abnormalities, declining school performance, and emotional
instability frequently dominate the clinical picture. In other patients,
cardiovascular signs are most prominent, and attention is focused
on a cardiac murmur or decreased exercise tolerance. Fatigability
and objective muscle weakness are observed in 60% to 70% of
patients. The pulse pressure widens, and the precordium may be overactive.
Other signs of sympathetic overactivity ...