Hypothyroidism is deficient thyroid hormone production. Symptoms in infants include poor feeding and growth failure; symptoms in older children and adolescents are similar to those of adults but also include growth failure, delayed puberty, or both. Diagnosis is by thyroid function testing (eg, serum thyroxine, thyroid-stimulating hormone). Treatment is thyroid hormone replacement.
(See also Overview of Thyroid Function.)
Etiology of Hypothyroidism in Infants and Children
Hypothyroidism in infants and young children may be congenital or acquired.
Congenital hypothyroidism
Congenital hypothyroidism occurs in about 1/2000 to 1/4000 live births (1). 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) (1, 2).
Dyshormonogenesis has multiple types, which can result from a defect in any of the steps of thyroid hormone biosynthesis (see Congenital Goiter).
Rarely in the United States but commonly in countries where iodine is not routinely added to table salt, hypothyroidism results from maternal iodine deficiency
Children with trisomy 21 have an increased risk of congenital hypothyroidism.
Acquired hypothyroidism
The most common cause of acquired hypothyroidism in the United States is
Autoimmune thyroiditis (Hashimoto thyroiditis)
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 and Turner syndrome are at increased risk of autoimmune thyroid disease. Children with other genetic conditions (eg, DiGeorge syndrome, Prader-Willi syndrome) are at increased risk of acquired hypothyroidism that is not autoimmune.
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 medications (eg, antiseizure medications, 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) or thyroid cancer.
Iodine deficiency remains the most common worldwide cause of hypothyroidism in children but is rare in the United States. Iodine deficiency may occur in children whose diet is restricted because of multiple food allergies or in those who require long-term parenteral nutrition.
Etiology references
1. Rose SR, Wassner AJ, Wintergerst KA, et al: Congenital Hypothyroidism: Screening and Management. Pediatrics 151(1):e2022060419, 2023. doi: 10.1542/peds.2022-060419
2. Persani L, Rurale G, de Filippis T, et al: Genetics and management of congenital hypothyroidism. Best Pract Res Clin Endocrinol Metab 32(4):387-396, 2018. doi: 10.1016/j.beem.2018.05.002
Symptoms and Signs of Hypothyroidism in Infants and Children
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 unconjugated 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 of Hypothyroidism). Signs specific to children are growth retardation, delayed skeletal maturation, and usually delayed puberty.
Diagnosis of Hypothyroidism in Infants and Children
Routine newborn screening
Thyroid function tests
Sometimes thyroid ultrasonography or radionuclide scan
Routine newborn screening detects hypothyroidism before clinical signs are evident (1). If screening is positive, confirmation is necessary with thyroid function tests, including measurement of free serum thyroxine (free T4) and thyroid-stimulating hormone (TSH) (2). 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. It is particularly important to measure free T4 rather than total T4 in preterm or low birthweight infants in whom alterations in binding proteins lead to low total T4 levels despite normal free T4 levels. Thyroid function tests are also done in older children and adolescents in whom hypothyroidism is suspected.
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 (3, 4). 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 anomaly (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 (5).
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. Central hypothyroidism may manifest in children with midline defects (eg, cleft palate, microphallus) or visual impairments (eg, nystagmus). Children confirmed to have central hypothyroidism should have MRI of the brain and pituitary to rule out central nervous system lesions. Alternatively this pattern of thyroid dysfunction develops in children who use certain medications (eg, antiseizure medications, immune checkpoint inhibitors) or who have certain illnesses (euthyroid sick syndrome). For children with euthyroid sick syndrome, thyroid function normalizes as the clinical status improves.
Diagnosis references
1. Wassner AJ: Congenital hypothyroidism. Clin Perinatol 45(1):1–18, 2018. doi: 10.1016/j.clp.2017.10.004
2. Rose SR, Wassner AJ, Wintergerst KA, et al: Congenital Hypothyroidism: Screening and Management. Pediatrics 151(1):e2022060419, 2023. doi: 10.1542/peds.2022-060419
3. van der Sluijs Veer L, Kempers MJ, et al: Health- related quality of life and self-worth in 10-year-old children with congenital hypothyroidism diagnosed by neonatal screening. Child Adolesc Psychiatry Ment Health 6(1):32, 2012. doi: 10.1186/1753-2000-6-32
4. Lichtenberger-Geslin L, Dos Santos S, Hassani Y, et al: Factors associated with hearing impairment in patients with congenital hypothyroidism treated since the neonatal period: a national population-based study. J Clin Endocrinol Metab 98(9):3644-3652, 2013. doi: 10.1210/jc.2013-1645
5. Odhaib SA, Mansour AA, Haddad NS: How Biotin Induces Misleading Results in Thyroid Bioassays: Case Series. Cureus 11(5):e4727, 2019. doi: 10.7759/cureus.4727
Treatment of Hypothyroidism in Infants and Children
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
Treatment of congenital hypothyroidism should be started if the confirmatory TSH level is > 20 mU/L (even if free T4 is normal). For TSH values between 10 and 20 mU/L, treatment can be started or alternatively TSH and free T4 levels can be closely monitored (every 1 to 2 weeks). Treatment is indicated for persistent TSH elevation > 10 mU/L (1).
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.
Older children who have only slight elevations in TSH (typically between 5 mU/L and 10 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, decreased growth velocity, 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. Thyroid testing should be repeated in patients with subclinical hypothyroidism because the majority of patients will have normalized TSH levels on repeat testing (1). Of note, patients with obesity may have subclinical hypothyroidism, but this is thought to be an adverse effect of obesity as opposed to a cause. Treatment is not recommended unless other factors (eg, positive thyroid antibodies, goiter) are present. Thyroid function will normalize with weight loss.
Treatment regimens
In congenital hypothyroidism,
In acquired hypothyroidism, the usual starting dose of levothyroxine often depends on degree of hypothyroidism at diagnosis. For severe, longstanding hypothyroidism, lower starting doses may be selected to avoid potential behavioral symptoms with slower titration to full dosing. Alternatively, dosing may be based on body surface area or on age and weight.
For both forms of hypothyroidism, the dose is titrated to maintain serum T4 and TSH levels within the normal range for age.
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 liquid formulations in congenital hypothyroidism, and it is unclear whether dosing is the same as for crushed tablets. If levothyroxine
Monitoring
Children are monitored more frequently during the first few years of life:
Every 1 to 2 months during the first 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.
Treatment references
1. Rose SR, Wassner AJ, Wintergerst KA, et al: Congenital Hypothyroidism: Screening and Management. Pediatrics 151(1):e2022060419, 2023. doi: 10.1542/peds.2022-060419
2. Lazar L, Frumkin RB, Battat E, et al: Natural history of thyroid function tests over 5 years in a large pediatric cohort. J Clin Endocrinol Metab 94(5):1678-1682, 2009. doi: 10.1210/jc.2008-2615
Key Points
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.
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
American Academy of Pediatrics: Congenital Hypothyroidism: Screening and Management (2023)
American Thyroid Association Task Force on Thyroid Hormone Replacement: Guidelines for the Treatment of Hypothyroidism (2014)
