Graves disease is definitively diagnosed by elevated T3 and T4 levels; suppressed TSH levels (< 0.1 mIU/L); elevated thyroid-stimulating antibody titers; and an ultrasound that reveals heterogeneous, hypoechoic tissue with increased blood flow. Thyroid peroxidase antibodies may also be positive in as many as 10% of patients with Graves disease. Radioactive iodine uptake scans show diffuse increased uptake throughout the thyroid gland (Figure 2).
Many uncommon causes of hyperthyroidism in adolescents are noted. Disorders with a similarly depressed TSH level include activating mutations of the TSH receptor and McCune-Albright syndrome, which is characterized by endocrine system hyperfunction, café au lait macules, precocious puberty, and fibrous dysplasia. Toxic adenomas, toxic multinodular goiter, drug-induced thyroiditis, subacute thyroiditis, and the thyrotoxic phase of Hashimoto thyroiditis can also have suppressed TSH levels and hyperthyroidism. However, these are all distinguished from Graves disease by lack of elevated TSIs and differences in radionucleotide uptake scans. Conditions with release of preformed thyroid hormone, such as subacute thyroiditis, demonstrate decreased radioactive iodine uptake.
Thyroid storm is rare, occurring in less than 1% of adults with hyperthyroidism and an unknown number of children. It is characterized by multisystem organ failure with gastrointestinal manifestations (nausea, vomiting, diarrhea, hepatic dysfunction), cardiovascular manifestations (tachycardia, arrhythmias, hypotension, congestive heart failure), and central nervous system manifestations (agitation, delirium, psychosis, stupor, coma), as well as hyperpyrexia. Thyroid storm is typically seen in patients with known thyroid disease after acute illness, surgery, abrupt cessation of antithyroid medications, or rarely after radioactive iodine therapy. However, thyroid storm can occur from prolonged untreated hyperthyroidism, and the general practitioner needs to remain aware of common symptoms of thyroid dysregulation as well as thyrotoxicosis or thyroid storm.
Treatment for hyperthyroidism in pediatric patients involves antithyroid drug therapy with methimazole (the only approved treatment in the United States for children and adolescents) or propylthiouracil or carbimazole.[1,2] These medications inhibit synthesis of thyroid hormone but may take several weeks to normalize thyroid hormone values. Patients with significant symptoms or thyrotoxicosis are started on beta-blockers to minimize adrenergic effects, such as tachycardia and hypertension. Definitive therapy, with a goal to become hypothyroid, involves either radioiodine ablation or total thyroidectomy.
Graves ophthalmopathy is a significant complication and involves inflammatory infiltrates and edema in retro-orbital tissue, which results in classic proptosis and diminished ocular muscle function. Symptoms of Graves ophthalmopathy are much more mild in children than in adults, and decreased vision is rare. Other complications of Graves disease include thyroid storm, which can be fatal, and medication or surgical side effects.
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