Hypothyroidism in Infants and Children

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 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.

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 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:

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.