(See also Overview of Thyroid Function Overview of Thyroid Function The thyroid gland, located in the anterior neck just below the cricoid cartilage, consists of 2 lobes connected by an isthmus. Follicular cells in the gland produce the 2 main thyroid hormones... read more .)
In infants, hyperthyroidism is rare but potentially life-threatening. It develops in fetuses of women with current or prior Graves disease Graves disease Thyroid disorders may predate or develop during pregnancy. Pregnancy does not change the symptoms of hypothyroidism and hyperthyroidism. Fetal effects vary with the disorder and the drugs used... read more . In Graves disease, maternal autoantibodies against the thyroid receptor for thyroid-stimulating hormone (TSH) 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 preterm birth due to fetal hyperactivity or tachycardia. 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% of cases. There is an increased incidence of Graves disease during puberty, with 80% of cases occurring after 11 years of age. The primary mechanism is stimulating antibodies for the TSH receptor. Other antibodies block the TSH receptor, and the balance between stimulating and blocking determines the severity of Graves disease. Many children with Graves disease have a family history of autoimmune thyroid disease or other autoimmune conditions. Children with trisomy 21 Down Syndrome (Trisomy 21) Down syndrome is an anomaly of chromosome 21 that can cause intellectual disability, microcephaly, short stature, and characteristic facies. Diagnosis is suggested by physical anomalies and... read more are at increased risk of Graves disease.
Less common causes of hyperthyroidism in children and adolescents include autonomously functioning toxic nodules, transient hyperthyroidism during the early phase of Hashimoto thyroiditis Hashimoto Thyroiditis Hashimoto thyroiditis is chronic autoimmune inflammation of the thyroid with lymphocytic infiltration. Findings include painless thyroid enlargement and symptoms of hypothyroidism. Diagnosis... read more 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 Subacute Thyroiditis Subacute thyroiditis is an acute inflammatory disease of the thyroid probably caused by a virus. Symptoms include fever and thyroid tenderness. Initial hyperthyroidism is common, sometimes followed... read more ) infections; bacterial causes include Staphylococcus aureus, S. epidermis, Streptococcus pyogenes, S. pneumoniae, Escherichia coli, and Clostridium septicum. Predisposing factors for acute thyroiditis in children include congenital anomalies (eg, persistent pyriform sinus fistula) and immunocompromised status.
Symptoms and Signs
In the fetus, hyperthyroidism is rare. Signs of hyperthyroidism (eg, poor intrauterine growth, fetal tachycardia [> 160 beats/minute], goiter) may be detected as early as the second trimester. Fetal hyperthyroidism may cause preterm labor. If fetal thyrotoxicosis is noted, the mother can be treated with antithyroid drugs. If fetal hyperthyroidism is not detected until the neonatal period, the infant may be severely affected; possible manifestations include craniosynostosis Craniosynostosis Craniosynostosis is premature fusion of one or more calvarial sutures. (See also Introduction to Congenital Craniofacial and Musculoskeletal Disorders and Overview of Congenital Craniofacial... read more (premature fusion of the cranial sutures), impaired intellect, growth failure, and short stature. Mortality rate may reach 10 to 15%.
In infants, symptoms and signs of hyperthyroidism include irritability, feeding problems, hypertension, tachycardia, exophthalmos, goiter ( see Congenital Goiter Congenital Goiter Congenital goiter is a diffuse or nodular enlargement of the thyroid gland present at birth. Thyroid hormone secretion may be decreased, increased, or normal. Diagnosis is made by confirming... read more ), frontal bossing, and microcephaly. Other early findings are failure to thrive, vomiting, and diarrhea. Affected infants almost always recover within 6 months; 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. More than 95% of children born to mothers with Graves disease present with symptoms within the first month of life; rarely, presentation is delayed into the second month.
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. Graves ophthalmopathy occurs in up to one third of children. Although eye findings are less dramatic than in adults, children may have eyelid lag or red or prominent eyes, sometimes with proptosis Proptosis This photo shows a woman's slightly bulging left eye (proptosis), caused by a meningioma. Proptosis is protrusion of the eyeball. Exophthalmos means the same thing, and this term is usually... read more (exophthalmos). Children and adolescents may present with alterations in growth, including growth acceleration and advanced bone age. The onset and progression through puberty are usually not affected by hyperthyroidism, with the exception of oligomenorrhea or amenorrhea noted in some girls.
Acute thyroiditis may occur at any age and manifests with sudden onset of symptoms of hyperthyroidism, tenderness over the thyroid gland, and fever. About 10% of patients with acute thyroiditis have hyperthyroidism. Many have leukocytosis with a left shift. 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 Thyroid storm Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more , 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.
Thyroid function tests
Sometimes thyroid ultrasonography or radionuclide scanning
In infants, hyperthyroidism is suspected if the mother has active Graves disease or a history of Graves disease and high titers of antibodies directed against the TSH receptor (thyroid-stimulating immunoglobulins [TSI] or TSH receptor antibodies [TRAb])
Hyperthyroidism is confirmed in the infant by measuring serum free thyroxine (T4), triiodothyronine (T3 Triiodothyronine (T3) measurement The thyroid gland, located in the anterior neck just below the cricoid cartilage, consists of 2 lobes connected by an isthmus. Follicular cells in the gland produce the 2 main thyroid hormones... read more ), and TSH Thyroid-stimulating hormone (TSH) measurement The thyroid gland, located in the anterior neck just below the cricoid cartilage, consists of 2 lobes connected by an isthmus. Follicular cells in the gland produce the 2 main thyroid hormones... read more . TSI is a functional assay that measures only stimulatory antibodies and is typically the first antibody measured to confirm Graves disease. TRAb is a competitive assay that measures both stimulating and blocking antibodies to the TSH receptor, but it does not distinguish between the different antibodies. TRAb may be measured in patients with symptoms and signs of thyrotoxicosis but with negative TSI. Because symptoms of hyperthyroidism may be nonspecific, neonates born to mothers with Graves disease are at risk of hyperthyroidism and should be monitored by measuring free T4 and TSH levels at 3 to 5 days of life and again at 10 to 14 days of life. If no biochemical abnormalities are noted, infants should be followed clinically until 2 to 3 months of life to identify those few with delayed presentation (1 Diagnosis references 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... read more , 2 Diagnosis references 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... read more ).
Diagnosis in older children and adolescents is similar to that in adults and also includes thyroid function tests (see diagnosis of hyperthyroidism Diagnosis Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more ) and measurement of TSI. Positive TSI in patients with symptoms and signs of thyrotoxicosis confirms the diagnosis of Graves disease. In contrast to the evaluation of hypothyroidism, measurement of T3 is essential because early in Graves disease, T3 may rise before T4 levels increase. Measurement of other thyroid antibodies, such as thyroid peroxidase and thyroglobulin, can help evaluate for possible hyperthyroid phase of autoimmune thyroiditis (hashitoxicosis). Biotin is a common over-the-counter supplement that can interfere with thyroid studies and should be stopped for at least 2 days before laboratory tests are done. Most commonly, biotin can result in falsely high levels of T4 and T3 and falsely low levels of TSH and can lead to an inappropriate diagnosis of hyperthyroidism.
Many clinicians do thyroid ultrasonography in older children with hyperthyroidism and thyroid gland asymmetry, negative TSI, or a palpable nodule. Ultrasonography or CT can also help localize an abscess or identify a congenital anomaly. Radionuclide scanning (with either technetium-99m pertechnetate or iodine-123) can also be done if the TSI level is not elevated to exclude an autonomously functioning toxic nodule or differentiated thyroid cancer. Radionuclide scanning shows diffuse uptake throughout the gland in Graves disease but shows increased uptake in the location of an autonomous nodule with reduced or absent uptake in the rest of the gland.
If a thyroid nodule is confirmed, fine-needle aspiration (FNA) biopsy should be considered. FNA biopsy can also help differentiate acute from subacute thyroiditis and provide a tissue sample for culture to allow testing of bacterial sensitivities for proper antibiotic coverage.
Sometimes radioactive iodine or surgery
Infants are given an antithyroid drug, typically methimazole 0.17 to 0.33 mg/kg orally 3 times a day, sometimes with a beta-blocker (eg, propranolol 0.8 mg/kg orally 3 times a day, atenolol 0.5 to 1.2 mg/kg orally 1 to 2 times a day) to treat symptoms. Propylthiouracil, another antithyroid drug, has 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. Lugol solution (potassium iodide) can be added 1 drop (0.05-mL) orally 3 times a day, with first dose given 1 hour after first methimazole dose, especially if refractory to methimazole and beta-blocker treatment. Hydrocortisone 0.8 to 3.3 mg/kg orally 3 times a day or prednisolone 1 mg/kg orally 2 times a day or 2 mg/kg once a day can also be considered, particularly in critically ill infants. Treatment of hyperthyroidism must be monitored closely and stopped as soon as the disease has run its course. Care must be taken to avoid iatrogenic hypothyroidism in infants treated with antithyroid drugs. (For treatment of Graves disease during pregnancy, see Graves disease Graves disease Thyroid disorders may predate or develop during pregnancy. Pregnancy does not change the symptoms of hypothyroidism and hyperthyroidism. Fetal effects vary with the disorder and the drugs used... read more .)
For children age 11 or older and adolescents (11 or older), treatment is similar to treatment of hyperthyroidism in adults Treatment Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more and includes antithyroid drugs and sometimes definitive therapy with thyroid ablation using radioactive iodine or surgery. Beta-blockers, such as atenolol or propranolol, may be used to control hypertension and tachycardia. Serious adverse effects of methimazole may include agranulocytosis; if patients taking methimazole develop febrile illness, they should have a complete blood count with differential. This usually occurs early in treatment with methimazole and at higher doses and, if detected, would be a contraindication to continuation of antithyroid drugs.
Children treated with antithyroid drugs are regularly monitored with thyroid function tests, typically every 4 to 6 weeks until a stable regimen is achieved and then every 3 to 4 months. Antithyroid drugs may be stopped if patients require only a low dose of methimazole to maintain a euthyroid state and/or have negative TSI. When these drugs are stopped, thyroid function tests should be repeated at regular intervals (4 to 6 weeks later then every 3 to 4 months throughout the next year). Children treated with antithyroid drugs have a 35% likelihood of remission, which is lower than that in adults (50%), and is defined as the lack of recurrence ≥ 12 months after antithyroid drugs have been stopped.
Definitive therapy may be needed for patients who do not achieve remission with 18 to 24 months 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 years and is often not effective in larger thyroid glands. Therefore, surgery may be preferable for children and adolescents who have these factors. Following definitive therapy, patients are started on levothyroxine. Doses may need to be adjusted based on weight gain or pubertal status.
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 (typically amoxicillin/clavulanic acid or cephalosporins for patients allergic to penicillin but ideally based on antibiotic sensitivities obtained from fine-needle aspiration biopsy specimen). Surgical treatment may be needed (eg, to drain an abscess or repair a fistula). Subacute thyroiditis is self-limiting, and nonsteroidal anti-inflammatory drugs are given for pain control. Antithyroid drugs are not indicated, but beta-blockers can be used if patients are symptomatic.
Hyperthyroidism in infants is usually caused by transplacental thyroid-stimulating antibodies from pregnant women 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 free thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH); thyroid-stimulating immunoglobulins (TSI) can be used to confirm Graves disease.
If there are significant palpable abnormalities of the thyroid, do ultrasonography.
Treat with methimazole and, for symptoms, a beta-blocker; however, only about 35% of cases acquired outside the neonatal period resolve with antithyroid drugs and patients may need definitive therapy using radioactive iodine or surgery.