(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, 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 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. Prepubertal children with Graves disease commonly present with isolated triiodothyronine (T3) toxicosis, but if diagnosis is delayed, they can have high levels of free serum thyroxine (T4) and high antibody titers directed against the TSH receptor. Some of the antibodies against the TSH receptor are stimulatory and some are blocking; the balance between these titers can determine the severity of Graves disease.
Symptoms and Signs
In the fetus, signs of hyperthyroidism (eg, poor intrauterine growth, fetal tachycardia [> 160 beats/minute], goiter) may be detected 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 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 by confirming thyroid... 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; however, puberty is often delayed Delayed Puberty Delayed puberty is absence of sexual maturation at the expected time. Diagnosis is by measurement of gonadal hormones (testosterone and estradiol), luteinizing hormone, and follicle-stimulating... read more rather than precocious Precocious Puberty Precocious puberty is onset of sexual maturation before age 8 in girls or age 9 in boys. Diagnosis is by comparison with population standards, x-rays of the left hand and wrist to assess skeletal... read more .
Acute thyroiditis may manifest 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 are many and include tachycardia, fatigue, weight loss, nervousness, 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, diagnosis of hyperthyroidism is suspected if their mother has active Graves disease or a history of Graves disease and high titers of stimulatory antibodies directed against the TSH receptor (thyroid-stimulating immunoglobulins [TSI] or TSH receptor antibodies [TRAb]) and is confirmed by measuring serum T4 Thyroxine (T4) 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 , free T4, 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 . Both TSI and TRAb can be used to confirm Graves disease. TSI measures only stimulatory antibodies, whereas TRAb measures both stimulating and blocking antibodies to the TSH receptor. TRAb may be used instead of TSI because the newer assays are highly sensitive in the diagnosis of hyperthyroidism and have faster turnaround times for results. 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 are many and include tachycardia, fatigue, weight loss, nervousness, and tremor... read more ) and measurement of TSI/TRAb. In contrast to the evaluation of hypothyroidism, measurement of T3 is essential because early in Graves disease, T3 may rise before T4 levels increase. Many clinicians do thyroid ultrasonography in older children with hyperthyroidism and thyroid gland asymmetry, negative TSI/TRAb, or a palpable nodule. Ultrasonography or CT can also help localize an abscess or identify a congenital anomaly. If a nodule is confirmed, fine-needle aspiration (FNA) biopsy should be considered as well as radionuclide scanning (either technetium-99m pertechnetate or I-123) to exclude an autonomously functioning toxic nodule or concurrent differentiated thyroid cancer. FNA biopsy can also help differentiate acute from subacute thyroiditis and provide 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 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. 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. (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 older children and adolescents, treatment is similar to treatment of hyperthyroidism in adults Treatment Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms are many and include tachycardia, fatigue, weight loss, nervousness, 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. 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.
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 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 (T4), free T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH); both thyroid-stimulating immunoglobulins (TSI) and TSH receptor antibodies (TRAb) 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.
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