(See also Overview of Thyroid Function.)
Hypothyroidism in infants and young children may be congenital or acquired.
Congenital hypothyroidism occurs in about 1/2000 to 1/3000 live births. Most congenital cases are sporadic, but about 10 to 20% are inherited. The causes usually involve
Dysgenesis may involve ectopy (two thirds of cases), absence (agenesis), or underdevelopment (hypoplasia) of the thyroid gland.
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 certain developing countries, hypothyroidism results from maternal iodine deficiency. 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.
The most common cause of acquired hypothyroidism in the US is
Autoimmune thyroiditis (Hashimoto thyroiditis)
Autoimmune thyroiditis occurs during later childhood and adolescence. About 50% of affected children have a family history 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) 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.
Symptoms and signs of hypothyroidism in infants and young children differ from those in older children and adults. If 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 : Symptoms and Signs). Signs specific to children are growth retardation, delayed skeletal maturation, and usually delayed puberty.
(See also the European Society for Paediatric Endocrinology's 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 (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 I-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 older 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. 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.
In most treated infants, motor and intellectual development is normal.
(See also the American Thyroid Association Task Force on Thyroid Hormone Replacement's guidelines for the treatment of hypothyroidism.)
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 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 (< 10 mU/L) and normal T4 or free T4 levels are considered to have subclinical hypothyroidism whether they have thyroid autoantibodies or not. Such children do not need thyroid replacement unless they develop symptoms of hypothyroidism or goiter or their levels of TSH increase.
In congenital hypothyroidism, treatment with L-thyroxine 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 L-thyroxine is based on body surface area (100 mcg/m2 orally once a day) or on age and weight as follows:
For both forms of hypothyroidism, the dose is titrated to maintain serum T4 and TSH levels within the normal range for age.
Thyroid replacement should be given only as a tablet, which can be crushed and made into paste for infants; it should not be given simultaneously with soy formula, or iron or calcium supplements, all of which can decrease thyroid hormone absorption.
Children are monitored more frequently during the first few years of life:
Older children can be monitored more frequently if there are concerns about adherence. After a dose adjustment in older children, TSH and 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 L-thyroxine, 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
American Thyroid Association Task Force on Thyroid Hormone Replacement: Guidelines for the treatment of hypothyroidism