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 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
Hypothyroidism in infants and young children may be congenital or acquired.
Congenital hypothyroidism
Congenital hypothyroidism occurs in about 1/1700 to 1/3500 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).
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 US but commonly in countries where iodine is not routinely added to table salt, hypothyroidism results from maternal iodine deficiency
Acquired hypothyroidism
The most common cause of acquired hypothyroidism in the US 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 are at increased risk of autoimmune thyroid disease.
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 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.
Etiology reference
1. Ford G, LaFranchi SH: Screening for congenital hypothyroidism: A worldwide view of strategies. Best Pract Res Clin Endocrinol Metab 28(2):175–187, 2014. doi: 10.1016/j.beem.2013.05.008
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 Hypothyroidism). Signs specific to children are growth retardation, delayed skeletal maturation, and usually delayed puberty.
Diagnosis
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). If screening is positive, confirmation is necessary with thyroid function tests, including measurement of free serum thyroxine (free T4) and thyroid-stimulating hormone
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.
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.
Diagnosis reference
1. Wassner AJ: Congenital hypothyroidism. Clin Perinatol 45(1):1–18, 2018. doi: 10.1016/j.clp.2017.10.004
Treatment
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 regimens
In congenital hypothyroidism,
In acquired hypothyroidism,2 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.
Monitoring
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.
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 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)
