(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 .)
Hypothyroidism in infants and young children may be congenital or acquired.
Congenital hypothyroidism occurs in about 1/1700 to 1/3500 live births (1 Etiology reference Hypothyroidism is thyroid hormone deficiency. Symptoms in infants include poor feeding and growth failure; symptoms in older children and adolescents are similar to those of adults but also... read more ). Most congenital cases are sporadic, but about 10 to 20% are inherited. Causes include
Dysgenesis of the gland (50 to 60% of cases)
Dyshormonogenesis (abnormal thyroid hormone production, 30 to 40% of cases)
Dysgenesis may involve ectopy (two thirds of cases), absence (agenesis), or underdevelopment (hypoplasia) of the thyroid gland. The cause is usually unknown, but an estimated 2 to 5% of cases are inherited, often in genes associated with thyroid gland formation (TSHR) or transcription factors (PAX8, NKX2-1).
Dyshormonogenesis has multiple types, which can result from a defect in any of the steps of thyroid hormone biosynthesis ( 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 ).
Rarely in the US but commonly in countries where iodine is not routinely added to table salt, hypothyroidism results from maternal iodine deficiency Iodine Deficiency In the body, iodine (I) is involved primarily in the synthesis of 2 thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Iodine occurs in the environment and in the diet primarily as... read more . Rarely, transplacental transfer of antibodies, goitrogens (eg, amiodarone), or antithyroid drugs (eg, propylthiouracil, methimazole) causes transient hypothyroidism. Another rare cause is central hypothyroidism, which is caused by structural anomalies in pituitary development; patients usually also have other pituitary hormone deficiencies. Children with trisomy 21 have an increased risk of congenital hypothyroidism.
The most common cause of acquired hypothyroidism in the US is
Autoimmune thyroiditis occurs most commonly during adolescence, but it also occurs in younger children, typically after the first few years of life. About 50% of affected children have a family history of autoimmune thyroid disease. 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 autoimmune thyroid disease.
Less commonly, hypothyroidism may occur after radiation therapy to the head and neck for certain cancers, after total body irradiation in preparation for bone marrow transplant, and secondary to certain drugs (eg, antiepileptic drugs, lithium, amiodarone, tyrosine kinase inhibitors). Permanent hypothyroidism is also the goal of therapy for patients undergoing definitive therapy for Graves disease (see treatment of hyperthyroidism in infants and children Treatment 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 ) or thyroid cancer Thyroid Cancers There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more .
Iodine deficiency Iodine Deficiency In the body, iodine (I) is involved primarily in the synthesis of 2 thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Iodine occurs in the environment and in the diet primarily as... read more remains the most common worldwide cause of hypothyroidism in children but is rare in the US. Iodine deficiency may occur in children whose diet is restricted because of multiple food allergies or in those who require long-term parenteral nutrition.
Symptoms and Signs
Symptoms and signs of hypothyroidism in infants and young children differ from those in older children and adults. If fetal iodine deficiency occurs very early during pregnancy, infants may present with severe growth failure, coarse facial features, intellectual disability, and spasticity.
Most other hypothyroid infants initially have few if any symptoms or signs and are detected only through newborn screening.
Symptoms that do occur may be subtle or develop slowly because some maternal thyroid hormone crosses the placenta. However, after the maternal thyroid hormone is metabolized, if the underlying cause of hypothyroidism persists and hypothyroidism remains undiagnosed or untreated, it usually slows central nervous system development moderately to severely and may be accompanied by low muscle tone, sensorineural hearing loss, prolonged hyperbilirubinemia, umbilical hernia, respiratory distress, macroglossia, large fontanelles, poor feeding, and hoarse crying. Rarely, delayed diagnosis and treatment of severe hypothyroidism lead to intellectual disability and short stature.
Some symptoms and signs of hypothyroidism in older children and adolescents are similar to those of adults (eg, weight gain; fatigue; constipation; coarse, dry hair; sallow, cool, or mottled coarse skin— see Symptoms and Signs Symptoms and Signs Hypothyroidism is thyroid hormone deficiency. Symptoms include cold intolerance, fatigue, and weight gain. Signs may include a typical facial appearance, hoarse slow speech, and dry skin. Diagnosis... read more ). Signs specific to children are growth retardation, delayed skeletal maturation, and usually delayed puberty.
Routine newborn screening
Thyroid function tests
Sometimes thyroid ultrasonography or radionuclide scan
(See also the European Society for Paediatric Endocrinology's 2014 consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism.)
Routine newborn screening detects hypothyroidism before clinical signs are evident (1 Diagnosis reference Hypothyroidism is thyroid hormone deficiency. Symptoms in infants include poor feeding and growth failure; symptoms in older children and adolescents are similar to those of adults but also... read more ). If screening is positive, confirmation is necessary with thyroid function tests, including measurement of free serum thyroxine 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) and thyroid-stimulating hormone 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 (TSH). These tests are also done in older children and adolescents in whom hypothyroidism is suspected. Free T4 is a better measure of thyroid function than total T4 in these patients because the levels of thyroid-binding proteins (thyroid-binding globulin, transthyretin, and albumin) affect total T4 levels. Measurement of triiodothyronine (T3) levels is rarely helpful in the diagnosis of hypothyroidism because it is the last test to show abnormal results and should not be done in most patients. Reverse T3 levels measure the metabolically inactive form of T3; reverse T3 increases during periods of illness or starvation and should not be measured to diagnose hypothyroidism.
Severe congenital hypothyroidism, even when treated promptly, may still cause subtle developmental problems and sensorineural hearing loss. Hearing loss may be so mild that initial screening misses it, but it may still interfere with language acquisition. Retesting after infancy is advised to detect subtle hearing loss.
When congenital hypothyroidism is diagnosed, radionuclide scanning (either technetium-99m pertechnetate or iodine-123) or ultrasonography can be done to evaluate the size and location of the thyroid gland and thus help distinguish a structural abnormality (ie, thyroid dysgenesis) from dyshormonogenesis and transient abnormalities.
In children and adolescents with suspected hypothyroidism (elevated TSH and low T4/free T4), thyroid antibody titers (to thyroid peroxidase and thyroglobulin) should be measured to evaluate for autoimmune thyroiditis. Biotin, a common over-the-counter supplement, should be stopped for at least 2 days before laboratory testing because it can interfere with several thyroid function tests. 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. Thyroid ultrasonography is not necessary to establish the diagnosis of autoimmune thyroiditis and should be restricted to children with thyroid gland asymmetry or palpable thyroid nodules.
Central hypothyroidism manifests with a pattern of low free T4 and non-elevated TSH levels. Children confirmed to have central hypothyroidism should have MRI of the brain and pituitary to rule out central nervous system lesions.
Thyroid hormone replacement
In most treated infants, motor and intellectual development is normal.
(See also the American Thyroid Association Task Force on Thyroid Hormone Replacement's 2014 guidelines for the treatment of hypothyroidism.)
When to treat
Most cases of congenital hypothyroidism require lifelong thyroid hormone replacement. However, if the initial TSH level is < 40 mU/L, an organic basis is not established, and the disease is thought to be transient (based on a lack of dose increase since infancy), clinicians may try stopping therapy after age 3 years, at which time the trial poses no danger to the developing central nervous system. If the TSH rises once therapy is stopped (typically allowing about 6 to 8 weeks off treatment) and the free T4 or T4 is low, permanent congenital hypothyroidism is confirmed and treatment should be restarted. Thyroxine-binding globulin deficiency, detected by screening that relies primarily on total serum T4 measurement, does not require treatment because affected infants have normal free T4 and TSH levels and are thus euthyroid.
Treatment with levothyroxine is indicated for children with a TSH level > 10 mU/L. Older children who have only slight elevations in TSH (typically between 5 mU/L and10 mU/L) and normal free T4 levels are considered to have subclinical hypothyroidism. There is controversy regarding treatment of patients with subclinical hypothyroidism. Subclinical hypothyroidism does not typically cause any symptoms. Treatment can be considered if patients have a goiter, positive thyroid antibodies, or hyperlipidemia. If not treated, thyroid function should be monitored every 6 to 12 months for a period of time to make sure function does not worsen.
In congenital hypothyroidism, treatment with levothyroxine 10 to 15 mcg/kg orally once a day must be started immediately and be closely monitored. This dosage is intended to rapidly (within 2 weeks) bring the serum T4 level into the upper half of the normal range for age (between 10 mcg/dL [129 nmol/L] and 15 mcg/dL[193 nmol/L]) and promptly (within 4 weeks) reduce the TSH.
In acquired hypothyroidism, the usual starting dosage of levothyroxine is based on body surface area (100 mcg/m2 orally once a day) or on age and weight as follows:
For ages 1 to 3 years: 4 to 6 mcg/kg once a day
For ages 3 to 10 years: 3 to 5 mcg/kg once a day
For ages 10 to 16 years: 2 to 4 mcg/kg once a day
For ages ≥ 17 years: 1.6 mcg/kg once a day
For both forms of hypothyroidism, the dose is titrated to maintain serum T4 and TSH levels within the normal range for age.
Levothyroxine is typically given in tablet form because of the inconsistent delivery of compounded liquid formulations prepared by individual pharmacists. Tablets can be crushed, mixed with a small amount (1 to 2 mL) of water, breast milk, or non–soy-based formula, and given orally by syringe. The absorption of levothyroxine may be decreased if it is given with soy formula, iron, or calcium. Commercial oral liquid formulations are available for children of any age and are available as single-dose ampules in different strengths or as 100-mL bottles with the dose selected by syringe volume. To date, there is limited experience with these newer liquid formulations in congenital hypothyroidism, and it is unclear whether dosing is the same as for crushed tablets. If levothyroxine must be given intravenously, 75% of the oral dose should be used. Although T3 is the biologically active thyroid hormone, levothyroxine (T4) is usually given and it is not necessary to use T3 because the majority of brain T3 arises through enzyme conversion of T4 to T3.
Children are monitored more frequently during the first few years of life:
Every 1 to 2 months during the 1st 6 months
Every 3 to 4 months between age 6 months and 3 years
Every 6 to 12 months from age 3 years to the end of growth
Older children can be monitored more frequently if there are concerns about adherence. After a dose adjustment in older children, TSH and free T4 levels are measured in 6 to 8 weeks.
Hypothyroidism in infants is usually congenital; acquired causes become more common with age.
Most congenital causes involve dysgenesis of the gland, but genetic disorders affecting thyroid hormone synthesis may occur.
Most hypothyroid infants are detected through routine newborn screening.
Confirm diagnosis with free serum thyroxine (free T4) and thyroid-stimulating hormone (TSH) levels; if confirmed, do imaging tests to detect structural thyroid disorders.
Treat with levothyroxine, adjusting the dose to maintain T4 and TSH levels within the normal range for age.
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
European Society for Paediatric Endocrinology: Consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism (2014)
American Thyroid Association Task Force on Thyroid Hormone Replacement: Guidelines for the treatment of hypothyroidism (2014)