Thyrotoxicosis refers to a hypermetabolic clinical syndrome due to excess production and secretion of endogenous (i.e., hyperthyroidism), or exogenous thyroid hormones. The term thyroid storm refers to an extreme state of decompensated thyrotoxicosis that is a potentially fatal thyroid emergency.

The most common cause of hyperthyroidism in children is Graves’ disease. This disease occurs in 1 in 5000 children, with a peak incidence between 11 and 15 years of age. The male to female ratio is 1:5.¹ Although the true incidence of childhood thyrotoxicosis is unknown, 5% of all thyrotoxicosis occurs in childhood,² and 0.6% to 10% of neonates born to mothers with Graves’ disease will show signs of thyrotoxicosis.³ The reported mortality in neonatal thyrotoxicosis is as high as 20%.³ Because childhood hyperthyroidism occurs mostly in adolescents, thyroid storm also occurs more frequently in this group (Fig. 79-1).²

Thyrotoxicosis results from thyroid hormone excess caused by either overproduction of thyroid hormone by the thyroid gland or by administration of synthetic hormone. Increased concentration of serum free thyroid hormone is almost always found in thyrotoxicosis. In Graves’ disease, activated B-lymphocytes produce antibodies against antigen shared by the thyroid gland and eye muscle.^1,4 Thyrotropin receptor-stimulating antibodies (TRSAb) bind to TSH receptors to increase thyroid hormone production. In congenital hyperthyroidism, transplacental transfer of TRSAb from the mother with Graves’ disease stimulates the thyroid gland to cause hyperthyroidism or thyrotoxicosis.^1,3,5

The actions of thyroid hormone at the cellular level include calorigenesis, acceleration of substrate turnover, amino acid and lipid metabolism, and stimulation of water and ion transport. Thyroid hormones also activate the adrenergic system by upregulation of β-adrenergic receptors causing symptoms of sympathetic nervous system overactivity, including hyperthermia. Why some individuals with hyperthyroidism have few symptoms and others develop the extreme clinical manifestation of thyroid hormone excess (thyroid storm), is still poorly understood. In thyroid storm, the clinical manifestations of thyroid hormone excess are thought to be because of an uncoupling of oxidative phosphorylation secondary to the illness, resulting in an enhanced rate of lipolysis, with fatty acid oxidation, increased oxygen consumption, calorigenesis, and hyperthermia. Specific conditions such as thyroid surgery, withdrawal of antithyroid medications, radioiodine therapy, palpation of a large goiter, and iodinated contrast dyes are known to precipitate thyroid storm in a patient with hyperthyroidism.

The causes of thyrotoxicosis may be divided into conditions in which the source of excess thyroid hormone is endogenous or exogenous (Table 79-1). The most common disorder causing thyrotoxicosis in children, as in adults, is the autoimmune disorder Graves’ disease.^2,6 In 5% to 10% of thyrotoxicosis, the cause is autoimmune thyroiditis, or Hashitoxicosis. In an even smaller percentage of patients, subacute thyroiditis can cause thyrotoxicosis because of destruction of thyroid tissue. This process is usually because of viral or granulomatous diseases, classically presenting with a painful thyroid gland, and is self-limited. Autonomously functioning thyroid nodules (toxic adenoma) are sometimes encountered in children.¹ Rarely, hyperthyroidism is secondary to TSH oversecretion from a pituitary tumor or because of congenital isolated pituitary resistance to negative feedback control by thyroid hormones. The possibility of a molar pregnancy, which produces a thyroid-stimulating hormone, must be considered in adolescent females with thyrotoxicosis.⁷ Administration of iodine-containing medications, such as radiocontrast, to patients with goiter may induce hyperthyroidism. Amiodarone causes thyrotoxicosis induced by its iodine content and destructive thyroiditis by its metabolites.⁸ Finally, thyrotoxicosis can occur as the result of intentional or iatrogenic excess thyroxine or triiodothyronine intake.