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Hyperthyroidism in Infants and Children

by Andrew Calabria, MD

Hyperthyroidism is excessive thyroid hormone production. Diagnosis is by thyroid function testing (eg, free serum thyroxine, thyroid-stimulating hormone). Treatment is with methimazole and sometimes radioactive iodine or surgery.

Etiology

In infants, hyperthyroidism is rare but potentially life-threatening. It develops in fetuses of women with current or prior Graves disease (see Graves disease). In Graves disease, patients have autoantibodies against the thyroid receptor for thyroid-stimulating hormone (TSH), and these autoantibodies overstimulate thyroid hormone production by binding to TSH receptors in the thyroid gland. These antibodies cross the placenta and cause thyroid hyperfunction in the fetus (intrauterine Graves disease), which can result in fetal death or premature birth. Because infants clear the antibodies after birth, neonatal Graves disease is usually transient. However, because the clearance rate varies, duration of neonatal Graves disease varies.

In children and adolescents, Graves disease is the cause of hyperthyroidism in > 90%. Less common causes include autonomously functioning toxic nodules, transient hyperthyroidism during the early phase of Hashimoto thyroiditis (see Hashimoto Thyroiditis) followed by eventual hypothyroidism (hashitoxicosis), or adverse drug effects (eg, amiodarone-induced hyperthyroidism). Occasionally, transient hyperthyroidism can be caused by infections, including bacterial (acute thyroiditis) and viral (subacute thyroiditis—see Subacute Thyroiditis) infections. Prepubertal children commonly present with isolated triiodothyronine (T 3 ) toxicosis, but if diagnosis is delayed, they can have high levels of free serum thyroxine (T 4 ) and high antibody titers directed against the TSH receptor.

Symptoms and Signs

In infants, symptoms and signs include irritability, feeding problems, hypertension, tachycardia, exophthalmos, goiter (see Congenital Goiter), frontal bossing, and microcephaly. Other early findings are failure to thrive, vomiting, and diarrhea. Affected infants almost always recover within 6 mo; the course is rarely longer. The onset and severity of symptoms also vary depending on whether the mother is taking antithyroid drugs. If the mother is not taking drugs, infants are hyperthyroid at birth; if the mother is taking drugs, infants may not become hyperthyroid until the drugs are metabolized at about 3 to 7 days.

Signs of hyperthyroidism (eg, poor intrauterine growth, fetal tachycardia [> 160 beats/min], goiter) may be detected in the fetus as early as the 2nd trimester. If fetal hyperthyroidism is not detected until the neonatal period, the infant may be severely affected; possible manifestations include craniosynostosis (premature fusion of the cranial sutures—see Craniosynostosis), impaired intellect, growth failure, and short stature. Mortality rate may reach 10 to 15%.

In children and adolescents , symptoms of acquired Graves disease may include sleep difficulties, hyperactivity, emotional lability, marked decrease in concentration and school performance, heat intolerance, diaphoresis, fatigue, weight loss, increased frequency of bowel movements, tremor, and palpitations. Signs include diffuse goiter, tachycardia, and hypertension. Although eye findings are less dramatic than in adults, children may have eyelid lag or red or prominent eyes, sometimes with proptosis (exophthalmos—see Proptosis). Prepubertal children are more likely to have a delayed diagnosis, which results in more chronic manifestations (eg, advanced bone age, increased height, decreased weight). Although they may have increased frequency of bowel movements, they usually do not have the palpitations or heat intolerance common in Graves disease.

Acute thyroiditis may manifest with sudden onset of symptoms of hyperthyroidism, tenderness over the thyroid gland, and fever. In subacute thyroiditis these manifestations are present but less severe and may have been preceded by a viral illness; fever may last for several weeks.

Thyroid storm (see Thyroid storm), a rare, severe complication in children with hyperthyroidism, may manifest with extreme tachycardia, hyperthermia, hypertension, congestive heart failure, and delirium, with progression to coma and death.

Diagnosis

  • Thyroid function tests

  • Sometimes thyroid ultrasonography or radionuclide scanning

Diagnosis is suspected in infants whose mothers have active Graves disease or a history of Graves disease and high titers of stimulatory antibodies (thyroid-stimulating immunoglobulins) and is confirmed by measuring T 4 , T 3 , and TSH.

Diagnosis in older children and adolescents is similar to that in adults and also includes thyroid function tests (see Hyperthyroidism : Diagnosis). T 3 levels help screen for isolated T 3 toxicosis. Many clinicians do thyroid ultrasonography in older children with Graves disease and thyroid gland asymmetry or a palpable nodule. If a nodule is confirmed, fine-needle aspiration biopsy should be considered as well as radionuclide scanning (either 99m Tc pertechnetate or 123 I) to exclude an autonomously functioning toxic nodule or concurrent differentiated thyroid cancer.

Treatment

  • Antithyroid drugs

  • Sometimes radioactive iodine or surgery

Infants are given an antithyroid drug, typically methimazole 0.17 to 0.33 mg/kg po tid, sometimes with a β-blocker (eg, propranolol 0.8 mg/kg po tid, atenolol 0.5 to 1.2 mg/kg po once/day to bid) to treat symptoms. Propylthiouracil, another antithyroid drug, has recently been found to sometimes cause severe liver failure and is no longer a first-line drug but may be used in special situations, such as thyroid storm. Treatment must be monitored closely and stopped as soon as the disease has run its course. (For treatment of Graves disease during pregnancy, see Graves disease.)

For older children and adolescents, treatment is similar to that for adults (see Hyperthyroidism : Treatment) and includes antithyroid drugs and sometimes definitive therapy with thyroid ablation using radioactive iodine or surgery. β-blockers, such as atenolol or propranolol, may be used to control hypertension and tachycardia. Children treated with antithyroid drugs have a 30% likelihood of remission, which is lower than that in adults (50%).

Definitive therapy may be needed for patients who do not achieve remission with 18 to 24 mo of antithyroid drug therapy, who have drug adverse effects, or who are nonadherent. Characteristics associated with lower likelihood of remission include younger age at onset (eg, prepubertal vs pubertal), higher thyroid hormone levels at initial presentation, larger thyroid gland (> 2.5 times normal size for age), and persistent elevation in TSH receptor antibody titers. Both radioactive iodine and surgery are reliable options for definitive therapy, with the goal of producing hypothyroidism. However, radioactive iodine is usually not used in children who are under age 10 yr and is often not effective in larger thyroid glands. Therefore, surgery may be preferable for children and adolescents who have these factors.

If an autonomously functioning toxic nodule is detected, surgical excision is recommended in children and adolescents.

Treatment of acute thyroiditis involves oral or IV antibiotics (amoxicillin/clavulanic acid or cephalosporins for patients allergic to penicillin). Subacute thyroiditis is self-limiting, and nonsteroidal anti-inflammatory drugs are given for pain control. Antithyroid drugs are not indicated, but β-blockers can be used if patients are symptomatic.

Key Points

  • Hyperthyroidism in infants is usually caused by transplacental thyroid-stimulating antibodies from mothers with Graves disease.

  • Hyperthyroidism in older children and adolescents is usually caused by Graves disease.

  • There are numerous manifestations of hyperthyroidism, including tachycardia, hypertension, weight loss, irritability, decreased concentration and school performance, and sleep difficulties.

  • Diagnosis is with serum thyroxine (T 4 ), free T 4 , triiodothyronine (T 3 ), and thyroid-stimulating hormone (TSH); if there are significant palpable abnormalities of the thyroid, do ultrasonography.

  • Treat with methimazole and, for symptoms, a β-blocker; however, only about 30% of cases acquired outside the neonatal period resolve with antithyroid drugs and patients may need definitive therapy using radioactive iodine or surgery.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • TAPAZOLE
  • CORDARONE
  • No US brand name
  • AMOXIL
  • TENORMIN
  • INDERAL

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