Pediatric Hypothyroidism 

Updated: Dec 20, 2016
Author: Sunil Kumar Sinha, MD; Chief Editor: Sasigarn A Bowden, MD 



The fetal hypothalamic-pituitary-thyroid system develops independently of the mother's pituitary-thyroid axis. During embryogenesis, primordial thyroid cells arise from epithelial cells on the pharyngeal floor; they then migrate caudally to fuse with the ventral aspect of the fourth pharyngeal pouch by 4 weeks' gestation. The thyroid continues to develop anteriorly to the third tracheal cartilage. Thyroglobulin is produced by 8 weeks' gestation. Trapping of iodine occurs by 10-12 weeks' gestation, followed by the synthesis of iodothyronines. Colloid formation and pituitary secretion of thyrotropin, also termed thyroid-stimulating hormone (TSH), occur by the 12 weeks' gestation.

Normal physiology

The primary function of the thyroid gland is synthesis of thyroxine (T4) and triiodothyronine (T3). Pituitary thyrotropin regulates thyroid hormone production. TSH synthesis and secretion are stimulated by thyrotropin-releasing hormone (TRH), which is synthesized by the hypothalamus and is secreted into the hypophyseal portal vasculature for transport to the anterior pituitary gland. Serum T4 concentration modulates secretion of both TRH and TSH by means of a classic negative feedback loop.

Circulating T4 is predominantly bound to T4-binding globulin (TBG). T4 is deiodinated in peripheral tissue to T3, the more bioactive thyroid hormone. T3 carries 3-4 times the metabolic potency of T4, freely enters cells, and binds to receptors of the hormone into the cell nucleus. Thyroid hormone exerts profound effects on the regulation of gene transcription. Some major clinical phenomena of thyroid hormone action include differentiation of the CNS and maintenance of muscle mass. Thyroid hormone also controls skeletal growth and differentiation and metabolism of carbohydrates, lipids, and vitamins.

Thyroid hormone synthesis absolutely requires iodine. Dietary iodine deficiency is endemic in several areas of the world, particularly high mountain plateaus. In the United States, supplementation of salt with iodine has nearly eliminated dietary deficiency of this essential element. The recommended dietary allowance of iodine is 40-50 mcg daily in infants, 70-120 mcg daily for children, and 150 mcg daily for adolescents and adults. The daily intake in North America varies from 240 mcg to more than 700 mcg.

In the thyroid gland, iodide is trapped, transported, and concentrated in the follicular lumen for thyroid hormone synthesis. Before trapped iodide can react with tyrosine residues, it must be oxidized by thyroidal peroxidase. Iodination of tyrosine forms mono-iodotyrosine and di-iodotyrosine. Two molecules of di-iodotyrosine combine to form T4, and one molecule of mono-iodotyrosine combines with one molecule of di-iodotyrosine to form T3. Formed thyroid hormones are stored within thyroglobulin in the lumen of the thyroid follicle until release. TSH stimulates uptake and organification of iodide as well as liberation of T4 and T3 from thyroglobulin.


Hypothyroidism is among the most common endocrine diseases. Congenital hypothyroidism most commonly results from agenesis, dysplasia, or ectopy of the thyroid; however, it is also caused by autosomal recessive defects in the organification of iodine (thyroid hormone synthesis) and defects in other enzymatic steps in T4 synthesis and release. In older children and adults, acquired hypothyroidism is most commonly caused by autoimmune destruction (Hashimoto thyroiditis).[1]



United States

Congenital hypothyroidism has a frequency of 1 case per 1500-3000 live births.[2]


Hypothyroidism can be congenital. Thyroid dysgenesis affects 1 per 4000 newborns worldwide. Hypothalamic or pituitary insufficiency, which results in secondary or tertiary hypothyroidism, respectively, affects 1 per 60,000-140,000 newborns worldwide.

Hypothyroidism can be acquired. Depending on the criteria used for diagnosis, as many as 10% of young females are estimated to have some signs of autoimmune thyroid disease, usually chronic lymphocytic thyroiditis (CLT). Not all cases progress to frank hypothyroidism; however, these patients remain at an increased risk compared with the general population.


Untreated congenital hypothyroidism in early infancy results in profound growth failure and disrupted development of the CNS, leading to developmental cognitive delay (cretinism). Untreated hypothyroidism in older children leads to growth failure as well as slowed metabolism and impaired memory.


In descending order, thyroid dysgenesis occurs more frequently in Hispanics than in whites, followed by blacks.


Thyroid dysgenesis occurs more frequently in females than in males, with a female-to-male ratio of 2:1. CLT also has a 4:1 female-to-male preponderance in childhood.


Congenital hypothyroidism can present with goiter at birth or with the gradual development of symptoms over the first several months of life.[3] The age of symptom onset is unpredictable in a child who has thyroid dysgenesis with a hypoplastic and/or ectopic thyroid gland because initial increases in TSH may be able to initially overcome the relative insufficiency of the thyroid gland. CLT typically presents during adolescence; however, it may present any time in life.




The history depends on the age at presentation.[4]

Congenital hypothyroidism

Most infants with congenital hypothyroidism are asymptomatic during the neonatal period or display subtle and nonspecific symptoms of thyroid hormone deficiency.

The lack of symptoms initially may result, in part, from an ectopic thyroid gland with clinically significant reserve function, partial defects in thyroid hormone synthesis, or to the moderate amount of maternal T4 that crosses the placenta and is able to boost fetal levels within 25-50% of normal levels observed at birth.

Detection of congenital hypothyroidism based on signs and symptoms alone may be delayed until age 6-12 weeks or older because of the protean clinical presentation and requires a high index of suspicion by the health care provider.

Only about 5% of infants with hypothyroidism are detected by clinical criteria before the biochemical screen alerts the clinician to confirm the diagnosis.

The following are among the earliest signs of hypothyroidism:

  • Prolonged gestation

  • Elevated birth weight

  • Delayed stooling after birth, constipation

  • Prolonged indirect jaundice

  • Poor feeding, poor management of secretions

  • Hypothermia

  • Decreased activity level

  • Noisy respirations

  • Hoarse cry

Acquired hypothyroidism

The clinical features of acquired hypothyroidism are typically insidious in onset.

  • Goiter: Patients with CLT (ie, Hashimoto thyroiditis) most commonly present with an asymptomatic goiter. Parents may report that their child's neck looks "full" or "swollen." Children may complain of local symptoms of dysphagia, hoarseness, or of a pressure sensation in their neck and/or throat. A patient with other causes of hypothyroidism may have an enlarged thyroid gland.

  • Slow growth, delayed osseous maturation, and increased weight: Mild weight gain despite decreased appetite is characteristic of the child who has a hypothyroid condition. Moderate-to-severe obesity in children is not typical for hypothyroidism. Furthermore, children with hypothyroidism manifest a decreased growth rate, a more constant finding than weight gain. In contrast, children with exogenous obesity typically have an increased growth velocity.

  • Lethargy

  • Decreased energy, dry skin, and puffiness

  • Sleep disturbance, typically obstructive sleep apnea

  • Cold intolerance and constipation

  • Heat intolerance, weight loss, and tremors: These are typical symptoms of hyperthyroidism. However, approximately 5-10% of children with CLT initially present with symptoms of toxic thyroiditis. This clinical picture may suggest a diagnosis of Graves disease. The thyrotoxic phase of CLT can be differentiated from Graves disease in that CLT is transient, is not associated with exophthalmos, and is usually associated with a decreased and nonuniform uptake of radioactive iodine. This hashitoxicosis phase is usually followed by the more characteristic hypothyroid phase.

  • Sexual pseudoprecocity

    • Parents may bring their child in for evaluation secondary to concern about testicular enlargement in boys or early breast development or onset of vaginal bleeding in girls.

    • The exact mechanism of sexual pseudoprecocity is not fully understood; however, TRH-induced TSH excess is thought to be the common stimulator of the follicle-stimulating hormone (FSH) receptor.

    • Serum FSH and luteinizing hormone (LH) levels are elevated into the pubertal range. Mounting evidence suggests that increased serum levels of prolactin produce resistance to LH stimulation of the gonads, perhaps leading to hypothalamic gonadotropin-releasing hormone (GnRH) production and stimulation of pituitary LH and FSH release.

    • The short stature and delayed bone age observed in children with hypothyroidism help distinguish sexual pseudoprecocity from true precocious puberty.

    • Sexual pseudoprecocity reverses with adequate thyroid replacement.

  • Galactorrhea: This condition develops in primary hypothyroidism secondary to TRH secretion from the hypothalamus. TRH stimulates the anterior pituitary to release TSH and prolactin. Galactorrhea resolves as prolactin concentrations fall with thyroid replacement.


If the newborn with congenital hypothyroidism is not identified by newborn screening and receives no replacement therapy, clinical manifestations of congenital hypothyroidism evolve during the first weeks after birth. Note that although the signs listed below are classic for congenital hypothyroidism, they may be subtle or absent. Recognition of this disorder has been enhanced by systematic newborn screening for the past 30 years.

Physical signs of congenital hypothyroidism include the following:

  • Bradycardia

  • Elevated weight

  • Sluggish behavior

  • Rare cry or hoarse cry (hoarse cry is secondary to myxedema of the vocal cords)

  • Large fontanelles

  • Myxedema of the eyelids, hands, and/or scrotum

  • Large protruding tongue (secondary to accumulation of myxedema in the tongue)

  • Goiter

  • Umbilical hernia

  • Delayed relaxation of deep tendon reflexes (The Achilles tendon reflex appears to be most sensitive to effects of hypothyroidism.)

  • Cool dry skin

  • Enlarged cardiac silhouette, usually because of pericardial effusion

  • Prolonged conduction time and low voltage on electrocardiogram (ECG)

  • Hypothermia

The signs of acquired hypothyroidism can include many physical findings observed with congenital hypothyroidism, such as the following:

  • Decreased growth velocity

  • Bradycardia

  • Mild obesity (5-15 lb over 6 mo) or morbid obesity (>20 lb overweight), which is seldom caused by hypothyroidism alone (The evaluation of obesity often includes assessment of serum TSH and free T4 levels.)

  • Immature upper-to-lower body proportions

  • Dry coarse hair

  • Delayed dentition

  • Precocious sexual development

  • Cool, dry, carotenemic skin

  • Brittle nails

  • Delayed relaxation phase of deep tendon reflexes

  • Goiter formation

    • This may occur secondary to the effects of TSH receptor–stimulating antibodies, inflammatory lymphocytic infiltration, or compensatory hyperplasia because of decreased serum T4 and increased TSH concentrations.

    • Typically, the thyroid gland is enlarged diffusely, although it may not be enlarged symmetrically.

    • Upon palpation, the thyroid gland may initially be soft but then takes on a firm feeling with rubbery consistency and a seedlike surface secondary to hyperplasia of the normal lobular architecture

  • Myxedema (much rarer in children than in adults)

  • Dull facial expression


Congenital hypothyroidism

Approximately 75% of infants with congenital hypothyroidism have defects in thyroid gland development, 10% have hereditary defects in thyroid hormone synthesis or uptake, 5% have secondary (pituitary) or tertiary (hypothalamus) hypothyroidism, and 10% have transient hypothyroidism.

  • Thyroid dysgenesis: Defective thyroid gland development accounts for most instances of congenital hypothyroidism. Thyroid dysgenesis occurs sporadically in most cases but is occasionally familial because of mutations or deletions of genes (TSHR, PAX8, NKX2-1, FOXE1, and NKX2-5) that are involved in fetal thyroid formation. Thyroid dysgenesis ranges in severity from thyroid aplasia or hypoplasia to functional ectopic thyroid tissue. Approximately 40-60% of infants with thyroid gland dysgenesis have some functioning tissue. Laboratory and imaging studies facilitate the determination of the degree of dysgenesis. Thyroid agenesis is suggested by a low serum T4 level with an elevated serum TSH level and undetectable serum thyroglobulin. Newborns with ectopic or hypoplastic thyroid glands manifest low serum T4, elevated serum TSH, and measurable levels of circulating thyroglobulin. Imaging aids in confirming the diagnosis of aplastic, hypoplastic, or ectopic thyroid.

  • Familial thyroid dyshormonogenesis: Rare autosomal recessive inborn errors of thyroid hormone synthesis, secretion, or uptake also cause congenital hypothyroidism. The following 8 inborn errors have been identified:

    • Failure to respond to TSH secondary to defective activation of the thyroid receptor and related cyclic adenosine monophosphate (cAMP) signal transduction pathway

    • Defect in trapping of iodide secondary to sodium-iodide symporter failure

    • Defective oxidation of iodide to iodine secondary to thyroid peroxidase deficiency

    • Defective coupling of iodotyrosines

    • Deiodination defects

    • Defective thyroglobulin synthesis

    • Defective proteolysis of thyroglobulin

    • Release of T3 and T4 into the circulation

  • Partial peripheral resistance to thyroid hormones (autosomal dominant defect): Patients relate a family history of goiter with euthyroidism or hypothyroidism in the face of elevated serum levels of T4 or T3 but nonsuppressed serum TSH concentrations.

  • Hypopituitarism

  • Transplacental passage of maternal TSH-binding inhibitory antibodies: This can cause transient neonatal hypothyroidism. In mothers with autoimmune thyroiditis, immunoglobulin G (IgG) antithyroid antibodies can be transmitted across the placenta. These antibodies block binding of TSH to its receptor on the fetal thyroid. The half-life of these antibodies is approximately 1 week, and this form of congenital hypothyroidism usually resolves within 2-3 months of life. Although these infants are asymptomatic, they require thyroid hormone replacement until the pituitary-thyroid axis recovers. Monitoring the infant's serum titer of maternal antibodies is unnecessary, although monitoring serum TSH values is essential for guiding therapy.

  • Maternal exposure to radioiodine: The fetal thyroid is able to trap iodide by 70-75 days' gestation. Hypothyroidism can develop if the mother is exposed to radioiodine to treat Graves disease or thyroid carcinoma.

  • Goitrogens: These include iodides found in certain asthma medications, amiodarone, neonatal exposure to iodine-containing antiseptics, propylthiouracil, or methimazole.

Acquired hypothyroidism

See the list below:

  • CLT (ie, autoimmune thyroiditis, Hashimoto thyroiditis) is the most common cause of acquired hypothyroidism and goiter in children living in iodine-sufficient areas. An increased frequency of CLT occurs in children with trisomy 21 syndrome, Ulrich-Turner syndrome, Klinefelter syndrome, or other autoimmune diseases, including type 1 diabetes mellitus. CLT appears to require both an environmental trigger and a genetically determined defect in immune surveillance.

  • Evidence suggests that the disease develops secondary to a defect in cell-mediated immunity whereby suppressor T lymphocytes fail to destroy forbidden clones of thyroid-directed T lymphocytes, which form as part of random immunologic differentiation. The attack on the thyroid involves natural killer cells and the complement cascade. Various thyroid autoantibodies (antithyroglobulin antibody, antithyroid peroxidase antibody) are demonstrable in the serum but are not believed to play a role in the pathogenesis of CLT.

  • Clinical manifestations of CLT vary depending on the type and predominance of thyroid antibodies produced. Most children present with an asymptomatic goiter and may be biochemically euthyroid, although compensated hypothyroidism and symptomatic hypothyroidism are more common presentations. Rarely, the child with CLT may be symptomatic with a small atrophied gland. A small percentage of children with CLT initially present with transient symptoms of hyperthyroidism. This short-lived thyrotoxic phase may be secondary to autonomous release of stored T4 and T3 (with progressive inflammatory lymphocytic infiltration of the thyroid) or secondary to an initial predominance of TSH-receptor stimulating immunoglobulins (termed hashitoxicosis).

  • Subacute thyroiditis is a rare disorder in children. Typically, a painful thyroid gland is accompanied by signs and symptoms of hyperthyroidism, with elevated serum T4 and suppressed serum TSH. Patients with this condition may present later manifesting a hypothyroid phase with goiter. The clinical hallmarks are painful swelling of the thyroid, usually after a viral infection, with lymphocytosis and elevated sedimentation rate. The inflammation results in autonomous release of thyroid hormone and a thyrotoxic phase, followed by a euthyroid phase and then a hypothyroid phase. Each phase lasts at least 1 week and is commonly followed by a return to an euthyroid state, depending on the degree of tissue damage. Treatment of the thyroid disorder is usually unnecessary.

  • Drug-induced hypothyroidism can result from use of thioamides, lithium, amiodarone, and excess dietary iodine. Exposure to these substances most often results in biochemical evidence of hypothyroidism in the absence of clinical symptoms.

  • Endemic goiter results from nutritional iodine deficiency with or without environmental goitrogen exposure. Endemic regions include high mountain plateaus and other areas that do not have ready access to salt water or seafood.

  • Euthyroid sick syndrome involves the following:

    • T4 is converted in peripheral tissues to bioactive T3 by thyroxine-5'-deiodinase enzyme. This enzyme is also responsible for clearing small amounts of reverse T3 (rT3), which are the by-products of T4 metabolism. Many nonthyroidal illnesses are associated with inhibition of 5'-deiodinase activity in peripheral tissues, resulting in a decrease of circulating bioactive T3 and an increase in reverse T3 (rT3).

    • Examples include acute or chronic severe illness, surgery, trauma, fasting, malnutrition, and use of certain drugs. TSH secretion is also decreased and does not appropriately respond to falling serum levels of T4. The classic findings include low or normal TSH, low T4 and free T4, low T3 and free T3, and elevated rT3 levels in serum. Thyroid hormone replacement is not needed because the disorder resolves with improvement of the underlying disease.

  • Childhood onset of congenital hypothyroidism secondary to hypoplastic or ectopic gland, which becomes unable to meet the demands of the growing child. Radioiodine uptake imaging assists in making the diagnosis.

  • Irradiation of the thyroid gland may be a cause. For example, the Chernobyl disaster of 1987 released massive quantities of radioactive iodine and cesium into the environment, leading to an increase in the subsequent incidence of both hypothyroidism and thyroid malignancy.

  • Infiltrative and storage disorders of the thyroid gland, including histiocytosis X and cystinosis, may be associated with hypothyroidism. In these instances, the primary disease is usually evident prior to the development of hypothyroidism.

  • Surgical excision may be associated with hypothyroidism.





Laboratory Studies

For all measures of thyroid function, age must be considered to interpret the results. In the term neonate, laboratory tests best reflect true thyroid function when performed in infants older than 24 hours.

  • Serum thyrotropin (TSH) concentration remains the most sensitive screening test for hypothyroidism and for establishing the diagnosis of primary hypothyroidism. The sample can be obtained at any time of day. A value within the reference range does not exclude TSH deficiency or TRH deficiency.

    • A physiologic surge of TSH occurs within the first 30 minutes of life and appears to be related to the stress of delivery and exposure to the cold temperature of the extrauterine environment. Serum TSH levels peak at levels as much as 70 mIU/L within the first 24 hours of life and then rapidly drop to less than 10 mIU/L within the first 3 days of life. Beyond the neonatal period, healthy serum levels of TSH are less than 6 mIU/L. Serum TSH levels are elevated in primary hypothyroidism or compensated hypothyroidism and should be low or within the reference range in cases of pituitary (TSH deficiency) or hypothalamic (TRH deficiency) etiologies. Isolated TSH deficiency is far less common than multiple anterior pituitary hormone deficiencies.

    • Serum TSH is the optimal parameter to guide dosing of thyroid hormone replacement, except in patients with secondary or tertiary hypothyroidism. In these patients, measuring serum free T4 by means of equilibrium dialysis is the superior testing method. Adequate thyroid hormone replacement results in normalization of serum TSH. In the rare syndromes of thyroid hormone resistance, serum TSH levels are elevated in the presence of normal-to-high serum total T4 concentration.

    • Serum TSH levels are often mildly abnormal (≤ 7 mIU/L) in children and adolescents who are morbidly obese (>20 lb overweight). If the serum free T4 level is normal, the growth velocity has been normal for at least 6 months, the serum TSH level remains stable (not rising) over at least 3 months, and no other signs of hypothyroidism are present, these children and adolescents do not require routine T4 therapy.

  • T4 is present in both the free state and bound to TBG. Total T4 assays measure T4 in both states and are useful to establish the diagnosis of primary hypothyroidism and to assess response to treatment. Free T4 should be directly measured with the equilibrium dialysis method. Many laboratories report a calculated value termed the free T4 index, which is an estimate of the free T4 concentration, not a measurement. The free T4 index is calculated by multiplying the T4 by the T3 resin uptake. Serum free T4 by equilibrium dialysis should be measured when secondary hypothyroidism (pituitary TSH deficiency) or tertiary hypothyroidism (hypothalamic TRH deficiency) is suggested.

  • Measurement of serum T3 concentration, free or total, is not required to confirm the diagnosis of hypothyroidism.

  • Newborn screening for congenital hypothyroidism includes the following:

    • Required by US law in all 50 states, these programs measure total T4 levels using a filter paper–based assay. In those neonates whose serum T4 level falls within the lowest 10th percentile for newborns screened that day by the program, T4 is reassayed, and TSH is simultaneously determined. Remember that, even with the best screening programs, infants with hypothyroidism can be missed. Therefore, the occurrence of a normal screening result must not preclude thyroid function testing in any infant with signs or symptoms of hypothyroidism.

    • Infants with abnormal or borderline screening results should have total T4 and TSH obtained for definitive testing. Thyroid hormone replacement may be empirically initiated while awaiting the confirmatory studies.

    • In infants, if the serum total T4 is less than 85 nmol/L (< 7 mg/dL), with TSH more than 40 mIU/L, congenital hypothyroidism is likely. If total T4 is low, and serum TSH is not elevated, TBG deficiency, central hypothyroidism, or euthyroid sick syndrome should be considered, and repeat testing may be needed.[5] Serum free T4 concentration is normal in TBG deficiency. Normal TSH (< 20 mIU/L) in the presence of low total T4 and free T4 concentrations suggest secondary or tertiary causes of hypothyroidism. In the latter, signs of associated hypopituitarism (eg, poor feeding, hypoglycemia) and physical findings (eg, midline defects, micropenis) support the diagnosis. All such infants should be screened for other pituitary hormone deficiencies (see Hypopituitarism).

  • Serum antithyroid antibody test findings do not facilitate the diagnosis of hypothyroidism and only serve to establish a diagnosis of CLT and indicate the risk of subsequent development of hypothyroidism. Antithyroid peroxidase and antithyroglobulin antibody titers are elevated in 90-95% of children with CLT. A small proportion of children with test results that are initially negative become positive later. As many as 20% of individuals who have antibody-positive test results do not develop hypothyroidism or hyperthyroidism.

  • Serum total T4 levels and serum free T4 levels are both low in patients with hypothyroidism. In compensated hypothyroidism, total T4 may remain within the reference range in the presence of elevated TSH.

  • Newborns with an elevated TSH should be treated empirically with thyroid hormone replacement until they are aged 2 years to eliminate any possibility of permanent cognitive deficits as a result of hypothyroidism.

  • Low or low-normal serum total T4 levels in the setting of a serum TSH within the reference range suggests TBG deficiency. This congenital disorder causes no pathologic consequence; however, it should be recognized to avoid unnecessary thyroid hormone administration. TBG deficiency affects 1 individual per 3000 population; therefore, occurrence is nearly as frequent as that in congenital hypothyroidism. TBG deficiency results in low serum total T4; however, serum TSH and serum free T4 concentrations are normal. Assessment of the serum TBG concentration, preferably with simultaneous serum free and serum total T4 concentrations, confirms the diagnosis.

Imaging Studies

See the list below:

  • In vivo radionucleotide studies: The iodide-trapping or concentrating mechanism of normal thyroid tissue can be evaluated by radioisotope (iodine-123 or technetium-99m pertechnetate). In children, technetium-99m is a useful radioisotope because it is trapped by the thyroid but not organified; thus, the child is exposed to lower amounts of radiation.

  • In congenital organification defects and lymphocytic thyroiditis, the amount of radioisotope uptake is within reference range; however, the half-life of the radioisotope within the thyroid is decreased because of the lack of organification. This can be demonstrated by means of a perchlorate washout study.

  • Radioisotope-based thyroid scanning is useful to detect the absence or ectopic location of healthy thyroid tissue in congenital hypothyroidism.

  • Iodine-123 scanning of the thyroid can be used to identify ectopic thyroid tissue, such as lingual thyroid. Absence of a signal on this study confirms athyreosis. 

  • X-ray of the knee can provide useful information regarding degree of severity of intrauterine hypothyroidism by the presence or absence of femoral and tibial epiphyses. [6]


Fine-needle aspiration is generally not necessary in children with hypothyroidism.

  • This study, which is designed to evaluate a thyroid nodule, should only be performed by a physician experienced with this procedure.

  • This procedure is most strongly indicated in adolescents or young adults who have a single cold nodule detected by means of iodine-123 scanning.

Histologic Findings

The histologic appearance of CLT includes lymphocytic infiltration, formation of lymphoid follicles, and follicular cell hyperplasia.



Medical Care

In congenital hypothyroidism, treatment should be initiated as soon as the diagnosis is suggested preferably before 2 weeks of life, immediately after obtaining blood for confirmatory tests. Delaying treatment after 6 weeks of life is associated with a substantial risk of delayed cognitive development. Recommended starting dose of levothyroxine for congenital hypothyroidism is 10 to 15 μg/kg/day.[6]  Newborns with elevated TSH should be treated empirically with thyroid hormone replacement until they are aged 2 years to eliminate any possibility of permanent cognitive deficits caused by hypothyroidism.

  • Once treatment is initiated for congenital hypothyroidism, serum total T4 and TSH concentrations should be assessed monthly until the total or free T4 levels normalize, then every 3 months until the patient is aged 3 years. Thereafter, total T4 and TSH should be measured every 6 months.

    • In patients with thyroid agenesis, serum TSH levels may remain slightly elevated (15-25 mcIU/mL) despite adequate thyroid hormone replacement, as indicated by serum total or serum free T4 levels and clinical assessment.

    • This phenomenon has been termed a reset thyrostat and reflects initial transient unresponsiveness of the hypothalamic-pituitary axis (hypertrophied thyrotrophs) to thyroid hormone replacement. The higher the initial serum TSH, the more likely one is to observe persistent mild elevation despite adequate replacement. If appropriate thyroid hormone replacement therapy is given, the thyrostat typically resets to a normal value within a few months.

  • Initial evaluation and follow-up can be conducted on an outpatient basis.

  • Bone age may confirm the diagnosis of congenital hypothyroidism or can be used to assess excessive thyroid hormone replacement.

  • Therapeutic goals are normalization of thyroid function test results and elimination of all signs and symptoms of hypothyroidism.

  • Therapy should correct growth, pseudoprecocious puberty, and galactorrhea. Goiter may be reduced; however, replacement therapy often does not result in complete normalization of size.

  • When indicated by an elevated serum TSH, dosage adjustments of 0.0125 mg levothyroxine are usually sufficient. Because the half-life of T4 in the serum is about 6 days, approximately 3.5 weeks are required for serum T4 values to reach a new steady state. Depending on the degree of hypothyroidism and the time spent in the hypothyroid state, suppression of elevated TSH levels may take longer; therefore, repeat measurements of total T4 and TSH should be obtained no sooner than 1 month after any dosage adjustment or change in brand of thyroid hormone.

  • Levothyroxine tablets are easily crushed and can be given in a spoon with a small amount of water, formula, or cereal. Suspensions are not commercially available and are not recommended because maintaining a consistent concentration of levothyroxine in solution is difficult.

  • Approximately 20% of children with CLT recover to the euthyroid state and do not require lifelong thyroid hormone replacement. After treatment beyond the completion of puberty, a 6-month trial off thyroid hormone replacement therapy should be considered, with monitoring of serum TSH and total T4 levels every 3 months. If serum TSH levels rise above the reference range, levothyroxine treatment should be resumed and continued for life. Patients with CLT should undergo at least yearly monitoring of thyroid function with serum total T4 and TSH assessment to assure adequate treatment and maintenance of euthyroidism.

  • In the case of concomitant hypopituitarism with corticotropin deficiency or any other causes of suspected adrenal insufficiency, glucocorticoid replacement should always precede thyroid hormone replacement. This reduces the risk of adrenal crisis resulting from increased demands from enhanced metabolism from thyroid hormone replacement.

Surgical Care

Rarely, a massive goiter may require surgical resection for cosmetic indications. Generally, surgical therapy has no role in the treatment of hypothyroidism. Case reports have documented surgical resection of an enlarged pituitary gland, which subsequently demonstrated physiologic thyrotroph hypertrophy related to primary hypothyroidism. This condition is best treated by adequate T4 replacement.


Consultation with a nuclear medicine physician is indicated for performance of radioiodine scan. Surgical consultation is advised during evaluation of a single cold nodule in the adolescent or young adult.


No dietary restrictions are necessary. However, soy-based formulas have been recognized to reduce the absorption of levothyroxine. Thus, these infants may require a slightly higher replacement dose to achieve euthyroidism.


Children with large pericardial effusions secondary to hypothyroidism should not participate in vigorous sports activities, until the effusion has resolved with T4 replacement. Such pericardial effusions from myxedema typically resolve within a month of attaining euthyroidism. No restriction of activity is required for patients with hypothyroidism who are euthyroid on replacement therapy.



Medication Summary

Levothyroxine is generally considered to be the treatment of choice for patients with hypothyroidism.

Thyroid Hormone

Class Summary

Levothyroxine is the preferred form of thyroid hormone replacement in all patients with hypothyroidism. Rarely, patients with congenital hypothyroidism display a "reset thyrostat" (ie, the serum TSH is not suppressed to reference range even with supraphysiologic replacement of levothyroxine). The primary therapeutic goal in patients with congenital hypothyroidism is to maintain the free serum T4 level within the high end of the reference range without resulting in symptoms of hyperthyroidism.

Thyroid hormones only should be used as replacement therapy in children with hypothyroidism. In active form, thyroid hormone influences growth and maturation of tissues, metabolism, and development. It does not enhance final adult height in euthyroid children.

Levothyroxine (Levothroid, Levoxyl, Synthroid)

Synthetic drug identical to human T4. Adjust dose on basis of total T4 and TSH (if primary hypothyroidism) or free T4 (if secondary or tertiary hypothyroidism); target range is normal total or free T4, with TSH < 5 mcU/mL. Use a single brand to avoid variations in potency between brands. Several commercial preparations are available and share equal efficacy, despite different potency. With age, dose decreases on a weight basis, although daily dose approximates 100 mcg/m2, IV dose is approximately 40-50% of the PO dose.



Further Outpatient Care

See the list below:

  • Once euthyroid, infants with congenital hypothyroidism should be observed every 3 months until they are aged 3 years. Thereafter, these children can be evaluated every 6 months.

Inpatient & Outpatient Medications

See the list below:

  • Levothyroxine is the appropriate replacement therapy for all clinically significant forms of hypothyroidism (see Medical Care).


See the list below:

  • Screening of newborns for hypothyroidism is required by law in all 50 US states.

  • One preventable cause of congenital hypothyroidism is avoidance of administration of radioiodine to women who are pregnant.[7] Thus, women should undergo pregnancy testing before receiving radioiodine.


See the list below:

  • The etiology of adverse clinical outcomes is multifactorial. Even with optimal therapy, some children with congenital hypothyroidism display intelligence quotient values lower than would be expected on the basis of genetic potential. Factors associated with this adverse outcome include a markedly low T4 value at birth, a markedly delayed bone age at diagnosis, delay in treatment, and low serum T4 levels during the first year of therapy.


See the list below:

  • The prognosis for patients with congenital hypothyroidism that is appropriately treated within 6 weeks of birth is excellent.

  • Children with acquired hypothyroidism who receive adequate treatment at least 5 years before the onset of puberty typically achieve a final adult height consistent with their genetic potential. Overtreating with thyroid hormone does not enhance catch-up growth and may compromise final adult height by advancing osseous maturation.