HIPOTIROID

Practice Essentials
Congenital hypothyroidism is inadequate thyroid hormone production in newborn infants. It can occur
because of an anatomic defect in the gland, an inborn error of thyroid metabolism, or iodine deficiency.
See the image below.

An infant with cretinism. Note the

hypotonic posture, coarse facial features, and umbilical hernia.
Signs and symptoms
Infants with congenital hypothyroidism are usually born at term or after term. Symptoms and signs
include the following:

Decreased activity
Large anterior fontanelle
Poor feeding and weight gain
Small stature or poor growth
Jaundice
Decreased stooling or constipation
Hypotonia

Hoarse cry
Often, affected infants are described as "good babies" because they rarely cry and they sleep most of the
time.
The physical findings of hypothyroidism may or may not be present at birth. Signs include the following:

Coarse facial features (wajah yang kasar)

Macroglossia
Large fontanelles
Umbilical hernia
Mottled, cool, and dry skin (kulit belang-belang, dingin, dan kering)
Developmental delay
Pallor (Pucat)
Myxedema (Bengkak2 seluruh tubuh, pucat dan kering)
Goiter (Pembesaran Tiroid)
Anemia may occur, due to decreased oxygen carrying requirement. A small but significant number (3-7%)
of infants with congenital hypothyroidism have other birth defects, mainly atrial and ventricular septal
defects.[1]
Diagnosis
Diagnosis of primary hypothyroidism is confirmed by demonstrating decreased levels of serum thyroid
hormone (total or free T4) and elevated levels of thyroid-stimulating hormone (TSH). If maternal

antibodymediated hypothyroidism is suspected, maternal and neonatal antithyroid antibodies may

confirm the diagnosis.[2] Such antibodies are an uncommon cause of congenital hypothyroidism.[3, 4]
The combination of low or low-normal serum total T4 levels and a serum TSH within the reference range
suggests thyroid-binding globulin (TBG) deficiency. This congenital disorder causes no pathologic
consequence, but should be recognized to avoid unnecessary thyroid hormone administration.
Thyroid scanning
Thyroid scanning is not required to make or confirm the diagnosis of congenital hypothyroidism, but can
provide important information about the etiology.
On thyroid scanning (using technetium-99m or iodine-123), the absence of radionuclide uptake suggests
sporadic athyreotic hypothyroidism but can also occur when uptake is blocked by excess iodide or thyroid
receptor blocking antibodies. If no uptake is found on isotope scanning, thyroid ultrasonography may
demonstrate thyroid tissue.[5]
Thyroid scans can also demonstrate the presence of an ectopic thyroid, such as a lingual or sublingual
gland, which is also sporadic. The presence of a bilobed thyroid in the appropriate position or a goiter
would suggest either an inborn error of thyroid hormone production or transient hypothyroidism or
hyperthyrotropinemia
Other imaging studies
Ultrasonography may be a reasonable alternative or addition to scintigraphy but may fail to reveal some
ectopic glands.[6]
A lateral radiograph of the knee may be obtained to look for the distal femoral epiphysis; this ossification
center appears at about 36 weeks' gestation, and its absence in a term or postterm infant indicates prenatal
effects of hypothyroidism.[7]
Management
The mainstay in the treatment of congenital hypothyroidism is early diagnosis and thyroid hormone
replacement. Optimal care may include diagnosis before age 10-13 days and normalization of thyroid
hormone blood levels by age 3 weeks.[8, 9]
Only levothyroxine is recommended for treatment.[10]Parents should be provided the hormone in pill form
and taught proper administration, as follows:

The pills can be crushed in a spoon; dissolved with a small amount of breast milk, water, or other
liquid immediately before administration; and administered to the child with a syringe or dropper

The pills should not be mixed in a full bottle of formula

Toddlers typically chew the tablets without problems or complaints.
Initial dosages of 10-15 mcg/kg/d, equivalent to a starting dose of 50 mcg in many newborns, have been
recommended.[11] Equally good developmental results, but with higher thyroid-stimulating hormone
(TSH) levels, have been reported with half this starting dose (25 mcg/d).[12]
Background
Congenital hypothyroidism is inadequate thyroid hormone production in newborn infants. This can occur
because of an anatomic defect in the gland, an inborn error of thyroid metabolism, or iodine deficiency.
The term endemic cretinism is used to describe clusters of infants with goiter and hypothyroidism in a
defined geographic area. Such areas were discovered to be low in iodine, and the cause of endemic

cretinism was determined to be iodine deficiency. In the 1920s, adequate dietary intake of iodine was
found to prevent endemic goiter and cretinism. [13] Endemic goiter and cretinism are still observed in some
areas, such as regions of Bangladesh, Chad, China, Indonesia, Nepal, Peru, and Zaire.
The term sporadic cretinism was initially used to describe the random occurrence of cretinism in
nonendemic areas. The cause of these abnormalities was identified as nonfunctioning or absent thyroid
glands. This led to replacement of the descriptive term sporadic cretinism with the etiologic term
congenital hypothyroidism. Treatment with thyroid replacement therapy was found to elicit some
improvement in these infants (see the images below), although many remained impaired.

An infant shown a few months after

starting thyroid hormone replacement.

Infant a few months after starting thyroid hormone

replacement.
The morbidity from congenital hypothyroidism can be reduced to a minimum by early diagnosis and
treatment.[14] Although initial preliminary studies were performed using thyroid-stimulating hormone
(TSH) levels in cord blood,[15, 16] mass screening was made feasible by the development of

radioimmunoassay for TSH and thyroxine (T4) from blood spots on filter paper, obtained for neonatal
screening tests.[17, 18]
Pathophysiology
The thyroid gland develops from the buccopharyngeal cavity between 4 and 10 weeks' gestation. The
thyroid arises from the fourth branchial pouches and ultimately ends up as a bilobed organ in the neck.
Errors in the formation or migration of thyroid tissue can result in thyroid aplasia, dysplasia, or ectopy.
By 10-11 weeks' gestation, the fetal thyroid is capable of producing thyroid hormone. By 18-20 weeks'
gestation, blood levels of T4 have reached term levels. The fetal pituitary-thyroid axis is believed to
function independently of the maternal pituitary-thyroid axis.
The thyroid gland uses tyrosine and iodine to manufacture T4 and triiodothyronine (T3). Iodide is taken
into the thyroid follicular cells by an active transport system and then oxidized to iodine by thyroid
peroxidase. Organification occurs when iodine is attached to tyrosine molecules attached to thyroglobulin,
forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). The coupling of 2 molecules of DIT forms
tetraiodothyronine (ie, T4). The coupling of one molecule of MIT and one molecule of DIT forms T3.
Thyroglobulin, with T4 and T3 attached, is stored in the follicular lumen. TSH activates the enzymes
needed to cleave T4 and T3 from thyroglobulin. In most situations, T4 is the primary hormone produced
by and released from the thyroid gland.
Inborn errors of thyroid metabolism can result in congenital hypothyroidism in children with anatomically
normal thyroid glands.
T4 is the primary thyronine produced by the thyroid gland. Only 10-40% of circulating T3 is released
from the thyroid gland. The remainder is produced by monodeiodination of T4 in peripheral tissues. T3 is
the primary mediator of the biologic effects of thyroid hormone and does so by interacting with a specific
nuclear receptor. Receptor abnormalities can result in thyroid hormone resistance.
The major carrier proteins for circulating thyroid hormones are thyroid-binding globulin (TBG), thyroidbinding prealbumin (TBPA), and albumin. Unbound, or free, T4 accounts for only about 0.03% of
circulating T4 and is the portion that is metabolically active. Infants born with low levels of TBG, as in
congenital TBG deficiency, have low total T4 levels but are physiologically normal. Familial congenital
TBG deficiency can occur as an X-linked recessive or autosomal recessive condition.
The contributions of maternal thyroid hormone levels to the fetus are thought to be minimal, but maternal
thyroid disease can have a substantial influence on fetal and neonatal thyroid function. Immunoglobulin G
(IgG) autoantibodies, as observed in autoimmune thyroiditis, can cross the placenta and inhibit thyroid
function. Thioamides used to treat maternal hyperthyroidism can also block fetal thyroid hormone
synthesis. Most of these effects are transient. Radioactive iodine administered to a pregnant woman can
ablate the fetus's thyroid gland permanently.
The importance of thyroid hormone to brain growth and development is demonstrated by comparing
treated and untreated children with congenital hypothyroidism. Thyroid hormone is necessary for normal
brain growth and myelination and for normal neuronal connections. The most critical period for the effect
of thyroid hormone on brain development is the first few months of life.[14]
Frequency
United States
The incidence of congenital hypothyroidism, as detected through newborn screening, is approximately 1
per 4000 births.[19] An increase in the diagnosis of primary congenital hypothyroidism has been reported in
New York.[20] This trend has also been observed in some other states, [21] although not all. Possible
explanations include changing demographics of the birth population, including changes in race, ethnicity,

and the incidence of low birth weight.[21] Changes in laboratory and screening methodology may also play
a role in this reported rise in incidence.[22] Some infants identified as having primary congenital
hypothyroidism may have transient disease and not permanent congenital hypothyroidism.[5]
Twins
An increased incidence of congenital hypothyroidism is observed in twins. [23, 24, 25] Twin births are
approximately 12 times as likely to have congenital hypothyroidism as singletons. [26] Usually, only one
twin is hypothyroid, but a common in-utero exposure can cause hypothyroidism in both. [27]
International
In central Africa, where iodine deficiency occurs along with excess dietary cyanate from cassava
(Manihot esculenta),[28] as many as 10% of newborns may have both low cord blood T4 concentration and
TSH concentrations over 100 mU/L.[29]
Data from most countries with well-established newborn screening programs indicate an incidence of
congenital hypothyroidism of about 1 per 3000-4000.[30, 31] Some of the highest incidences (1 in 1400 to 1
in 2000) have been reported from various locations in the Middle East. [32]
Although percentages of specific etiologies vary from country to country, ranges are as follows:

Ectopic thyroid - 25-50%

Thyroid agenesis - 20-50%
Dyshormonogenesis - 4-15%
Hypothalamic-pituitary dysfunction - 10-15%
Mortality/Morbidity
Congenital hypothyroidism does not affect the all-cause standardized mortality ratio in treated patients. [33]
Profound mental retardation is the most serious effect of untreated congenital hypothyroidism. Severe
impairment of linear growth and bone maturation also occurs. Affected infants whose treatment is delayed
can have neurologic problems such as spasticity and gait abnormalities, dysarthria or mutism, and autistic
behavior.
Race
Congenital hypothyroidism is observed in all populations. The prevalence at birth is increased in
Hispanics, particularly in Hispanic females, who have a birth prevalence of 1 in 1886 births. [34] Black
infants have about one third the prevalence rate of white infants.
Sex
Most studies of congenital hypothyroidism suggest a female-to-male ratio of a 2:1. Devos et al showed
that much of the discrepancy is accounted for by infants with thyroid ectopy.[35] The sex ratio for
Hispanics is more striking, with a 3:1 female-to-male ratio. The ratio is lower among Black infants.
Age
By definition, congenital hypothyroidism is present at, or before, birth. Children who develop primary
hypothyroidism when aged 2 years or older have poor growth and slow mentation but generally do not
exhibit the profound and incompletely reversible neurologic abnormalities observed in untreated
congenital hypothyroidism.
History

In regions of iodide deficiency and a known prevalence of endemic cretinism, the diagnosis may be
straightforward.
Infants with congenital hypothyroidism are usually born at term or after term.
Symptoms and signs include the following:

Decreased activity
Large anterior fontanelle
Poor feeding and weight gain
Small stature or poor growth
Jaundice
Decreased stooling or constipation
Hypotonia
Hoarse cry
Often, they are described as "good babies" because they rarely cry and sleep most of the time.
Family history should be carefully reviewed for information about similarly affected infants or family
members with unexplained mental retardation.
Maternal history of a thyroid disorder and mode of treatment, whether before or during pregnancy, can
occasionally provide the etiology of the infant's problem.
Congenital hypothyroidism is more common in infants with birthweights less than 2,000 g or more than
4,500 g.[36, 24]
Congenital hypothyroidism is more common in multiple births, with a low concordance rate. [26]
Physical
The physical findings of hypothyroidism may or may not be present at birth (see the image below).

An infant with cretinism. Note the

hypotonic posture, coarse facial features, and umbilical hernia.
Signs include the following:

Coarse facial features

Macroglossia (See the image below.)

Note the macroglossia.

Large fontanelles
Umbilical hernia
Mottled, cool, and dry skin
Developmental delay
Pallor
Myxedema
Goiter
A small but significant number (3-7%) of infants with congenital hypothyroidism have other birth defects,
mainly atrial and ventricular septal defects.[1]
Newborn screening involves the following:

Infants with congenital hypothyroidism are usually identified within the first 2-3 weeks of life.
These infants should be carefully examined for signs of hypothyroidism, and the diagnosis should
be confirmed by repeat testing.

Infants with obvious findings of hypothyroidism (eg, macroglossia, enlarged fontanelle,

hypotonia) at the time of diagnosis have intelligence quotients (IQs) 10-20 points lower than infants
without such findings.
Anemia may occur, due to decreased oxygen carrying requirement.
Causes
Endemic cretinism is caused by iodine deficiency, and is occasionally exacerbated by naturally occurring
goitrogens.[37]
Dysgenesis of the thyroid gland, including agenesis (ie, complete absence of thyroid gland) and ectopy
(lingual or sublingual thyroid gland) may be a cause.
Inborn errors of thyroid hormone metabolism include dyshormonogenesis. Most cases are familial and
inherited as autosomal recessive conditions. These may also include the following:

Thyroid-stimulating hormone (TSH) unresponsiveness (ie, TSH receptor abnormalities) [38]

Impaired ability to uptake iodide
Peroxidase, or organification, defect (ie, inability to convert iodide to iodine)
Pendred syndrome, a familial organification defect associated with congenital deafness
Thyroglobulin defect (ie, inability to form or degrade thyroglobulin)
Deiodinase defect
Thyroid hormone resistance (ie, thyroid hormone receptor abnormalities) may also be a cause. [38]
In maternal autoimmune disease, transplacental passage of antibodies cause transient or permanent
hypothyroidism.[2, 39]
Radioactive iodine therapy of pregnant women may cause permanent congenital hypothyroidism. Iodine
in contrast agents or skin disinfectants can cause hypothyroidism or hyperthyrotropinemia in premature
neonates.[40]
TSH or thyrotropin-releasing hormone (TRH) deficiencies are also noted. Hypothyroidism can also occur
in TSH or TRH deficiencies, either as an isolated problem or in conjunction with other pituitary
deficiencies (eg, hypopituitarism). If present with these deficiencies, hypothyroidism is usually milder
and is not associated with the significant neurologic morbidity observed in primary hypothyroidism.
Diagnostic Considerations
Neonatal hypothyroxinemia
Premature and sick infants have lower levels of thyroid hormone than term infants but usually do not have
elevated thyroid-stimulating hormone (TSH) levels. [41, 42] Reference ranges appropriate to the infant's
gestational age should be used to avoid confusing this with hypothyroidism. A meta-analysis suggests that
treatment of these neonates with thyroxine is futile. [43]
Transient neonatal hypothyroidism and hyperthyrotropinemia
Ingestion of excessive amounts of iodine,[44] or of goitrogens such as lithium,[45] thioamides,[46, 27] or
amiodarone,[47, 48] can cause a temporary hypothyroid state. Maternal antibodies to the TSH receptor can
also cause temporary hypothyroidism.[2, 39, 3] This may require treatment with levothyroxine for a period of
days to months. The etiology of transient hypothyroidism is often unclear.[5, 49, 50] Preterm (< 35 wk
gestation) infants may have profound abnormalities of thyroid function at birth, but they may not have
permanent hypothyroidism, even in infants with birth weights of greater than 1500 grams. [51]
Differential Diagnoses

Beckwith-Wiedemann Syndrome

Goiter

Iodine Deficiency

Panhypopituitarism

Pediatric Hypopituitarism

Thyroxine-Binding Globulin Deficiency

Laboratory Studies
Diagnosis of primary hypothyroidism is confirmed by demonstrating decreased levels of serum thyroid
hormone (total or free T4) and elevated levels of thyroid-stimulating hormone (TSH).
If maternal antibodymediated hypothyroidism is suspected, maternal and neonatal antithyroid antibodies
may confirm the diagnosis.[2] Such antibodies are an uncommon cause of congenital hypothyroidism. [3]
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. Thyroid-binding globulin (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 levels; 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.
TBG levels can be measured in infants with suspected TBG deficiency. This condition does not require
treatment, but appropriate diagnosis and parental counseling can avoid later confusion and misdiagnosis.
Routine laboratory testing in patients with TBG deficiency shows a low total T4 level and a TSH level
within the reference range. Free T4 and T3 levels are within the reference range. Congenital nephrotic
syndrome is a rare cause of TBG deficiency or congenital hypothyroidism. [52, 53]
Laboratory results similar to infants with TBG deficiency can be found in infants who
have hypopituitarism or hypothalamic disease, but these children have normal TBG levels.
Imaging Studies
Thyroid scanning (using technetium-99m or iodine-123) may be useful in defining the cause of
hypothyroidism and may aid in genetic counseling. It can aid in distinguishing congenital hypothyroidism
from transient hyperthyrotropinemia.[54, 5] The absence of radionuclide uptake suggests sporadic athyreotic
hypothyroidism but can also be seen when uptake is blocked by excess iodide or thyroid receptor
blocking antibodies. If no uptake is found on isotope scanning, thyroid ultrasonography may demonstrate
thyroid tissue in these patients.[5, 55] One study of 210 scanned infants stated a preference for using iodine123 over pertechnetate.[56]
Thyroid scans can also demonstrate the presence of an ectopic thyroid, such as a lingual or sublingual
gland, which is also sporadic. The presence of a bilobed thyroid in the appropriate position or a goiter
would suggest either an inborn error of thyroid hormone production or transient hypothyroidism or
transient hyperthyrotropinemia. Thyroid scanning is not required to make or confirm the diagnosis of
congenital hypothyroidism, but can provide important information about the etiology.

Ultrasonography may be a reasonable alternative or addition to scintigraphy but may fail to reveal some
ectopic glands.[6, 57]
A lateral radiograph of the knee may be obtained to look for the distal femoral epiphysis. This ossification
center appears at about 36 weeks' gestation. Its absence in a term or postterm infant indicates prenatal
effects of hypothyroidism, and prior to the introduction of hormone measurements, was used as a
diagnostic test for congenital hypothyroidism. [7]
Early studies of outcome suggested that infants without a distal femoral epiphysis did less well than those
with one, although both groups had results in the normal range. [58] The author of this study was later
unable to demonstrate an effect of bone age at diagnosis on outcome. [59] Another study was unable to
demonstrate any difference in outcome in infants with or without a distal femoral epiphysis. [60]
Other Tests
Neonatal hypothyroidism screening, using TSH levels, has proven helpful in countries with mild to no
iodine deficiency. It has not been found useful in countries with moderate-to-severe levels of iodine
deficiency disorders (IDD) because resources are insufficient to deal with the problem, and efforts here
should be made to supply sufficient iodine to the population as a whole.
In infants with suspected dyshormonogenesis, radioactive iodine uptake (iodine-123) and perchlorate
flush testing (KCIO2) can be performed to determine the presence of an iodide uptake or organification
defect.

Medical Care
The mainstay in the treatment of congenital hypothyroidism is early diagnosis and thyroid hormone
replacement. Optimal care may includes diagnosis before age 10-13 days and normalization of thyroid
hormone blood levels by age 3 weeks.[8, 9, 61]
Consultations
The treatment of hypothyroidism is straightforward. However, because of the potential for serious
morbidity with inadequate treatment or overtreatment, primary physicians should consult a pediatric
endocrinologist. Appropriate psychological, developmental, and educational evaluations should also be
considered.
Diet
Dietary iodide supplementation in iodine-deficient areas can prevent endemic cretinism but does not have
a major effect on sporadic congenital hypothyroidism. Dietary iodine deficiency is the most common
preventable cause of brain damage worldwide.[62]
Soy-based formulas may decrease the absorption of levothyroxine. [63] This is not a contraindication to
their use, even in infants with congenital hypothyroidism. Switching an infant from a milk-based formula

to a soy-based formula may increase the dose of thyroid hormone needed to maintain a euthyroid status.
[64]

Activity
Activity should be encouraged in children with congenital hypothyroidism, because activity should be
encouraged in all children.
Medication Summary
Only levothyroxine is recommended for treatment. [10] It has been established as safe, effective,
inexpensive, easily administered, and easily monitored. Some authors suggest that generic forms may be
just as effective as branded medications,[65] but others diasagree.[66]
No liquid preparations are commercially available in the United States, but they are licensed elsewhere.
[67]
Pharmacies should be discouraged from dispensing suspensions prepared in-house by crushing tablets
and mixing with various agents. The T4 in these preparations is very difficult to keep in suspension, and
the delivery of drug is inconsistent.
Parents should be provided the hormone in pill form and taught proper administration. The pills can be
crushed in a spoon; dissolved with a small amount of breast milk, water, or other liquid immediately
before administration, and administered to the child with a syringe or dropper. The pills should not be
mixed in a full bottle of formula. Toddlers readily chew the tablets without problems or complaints.
Optimum dosage regimens and follow-up laboratory monitoring have not yet been determined. [68, 69,
70]
Initial dosages of 10-15 mcg/kg/d, equivalent to a starting dose of 50 mcg in many newborns, have been
recommended.[11] Equally good developmental results, but with higher thyroid-stimulating hormone
(TSH) levels, have been reported with half this starting dose (25 mcg/d). [12]
Thyroid Hormones
Class Summary
These agents are administered to supplement thyroid hormone in patients with hypothyroidism.
Levothyroxine is the preferred form of thyroid hormone replacement in all patients with hypothyroidism.
[71]
Desiccated thyroid is an obsolete medication made from pooled animal tissue. Desiccated thyroid
should not be used.
View full drug information
Levothyroxine (Levothroid, Levoxyl, Synthroid)
Also known as L-thyroxine, T4, and thyroxine. A thyroid hormone with proven record of safety, efficacy,
and ease of use. In active form, influences growth and maturation of tissues. Involved in normal growth,
metabolism, and development.

Dosage Forms & Strengths

tablet

25mcg, 50mcg, 75mcg, 88mcg, 100mcg, 112mcg

125mcg, 137mcg, 150mcg, 175mcg, 200mcg, 300mcg

capsule (Tirosint)

13mcg, 25mcg, 50mcg, 75mcg, 88mcg

100mcg, 112 mcg, 125mcg, 137 mcg, 150mcg

powder for injection

200mcg/vial

500mcg/vial

Hypothyroidism
Age 1-3 months
10-15 mcg/kg/day PO
5-7.5 mcg/kg/day IV/IM
Use lower starting dose (25 mcg/day) if patient at risk of cardiac failure; if initial serum T4 lower
than 5 mcg/dL begin treatment at higher dose (50 mcg/day)
Age 3-6 months
8-10 mcg/kg/day PO, OR
25-50 mcg/day PO
4-7.5 mcg/kg/day IV/IM
Age 6-12 months
6-8 mcg/kg/day PO, OR
50-75 mcg/day PO
3-6 mcg/kg/day IV/IM
Age 1-5 years
5-6 mcg/kg/day PO, OR
75-100 mcg/day PO
2.5-4.5 mcg/kg/day IV/IM
Age 6-12 years
4-5 mcg/kg/day PO, OR
100-125 mcg/day PO
2-3.75 mcg/kg/day IV/IM
>12 years
2-3 mcg/kg/day PO, OR
150 mcg/day PO
1-2.25 mcg/kg/day IV/IM
Dosing considerations
Check for bioequivalence if switching brands/generics
May minimize hyperactivity in older children by initiating dose at 1/4 of recommended dose;
increase by that amount each week until full dose achieved
Start children with severe or chronic hypothyroidism at 25 mcg/day; adjust dose by 25 mcg
qweek
Administration

Take tabs with full glass of water before breakfast on empty stomach
Do not use foods that decrease absorption (soybean infant formula) for administering levothyroxine
Administer oral levothyroxine >4 hr apart from drugs known to interfere with absorption
IV/IM 50-75% of PO
Patients unable to swallow intact tabs/caps

Tablets: Crush appropriate dose and place in 5-10 mL of water; administer resultant suspension
by spoon or dropper immediately, do NOT store

Capsules: Do not administer capsule to children unable to swallow capsule whole

Pharmacology
Mechanism of Action
Synthetic T4; thyroid hormone increases basal metabolic rate, increases utilization and mobilization of
glycogen stores, promotes gluconeogenesis; involved in growth development and stimulates protein
synthesis
Absorption
40-80% from GI tract (PO)
Bioavailability: 64% (nonfasting); 79-81% (fasting)
Peak plasma time: 2-4 hr (PO)
Duration: Hypothyroidism, several weeks
Onset, hypothyroidism

Initial response: 3-5 days (PO); 6-8 hr (IV)

Maximum effect: Several weeks

Peak effect: 24 hr (IV)

Onset, myxedema coma

Initial response: 6-12 hr (IV)

Peak effect: 24 hr
Distribution
Protein bound: 99%
Vd: 9-10 L
Metabolism
Deiodinated in blood and then 50% converted to active metabolite, triiodothyronine (T3), also by liver
Metabolites: T3 (active)
Elimination
Half-life: 9-10 days (hypothyroid); 3-4 days (hyperthyroid); 6-7 days (euthyroid)
Total body clearance: 0.8-1.4 L/day

Excretion: Urine (major), feces (20%)

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).
Deterrence/Prevention
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.[5] Thus, women should undergo pregnancy testing before
receiving radioiodine.
Complications
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.
Prognosis
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.