Congenital hypothyroidism (CH) is a condition characterized by an inadequate production of thyroid hormones among newborns. It can occur due to prenatal iodine deficiency, anatomical anomaly in the gland or from inborn errors in thyroid metabolism. Deficiency of thyroid hormones at birth is mostly related to a problem with the development of the thyroid gland, also known as dysgenesis, or the inability to synthesize thyroid hormones, also known as dyshormonogenesis.
The symptoms of congenital hypothyroidism are usually subtle or not present at birth, that is the reason many neonates go undiagnosed at birth  . Passage of maternal thyroid hormone through the placenta to the infant is one of the reasons that leads late diagnosis of congenital hypothyroidism.
The most common presentation includes cold or mottled skin, macroglossia or umbilical hernia seen at the initial examination . Wide posterior fontanel greater than 5 mm may also be seen. Other important features include poor feeding and persistence of jaundice . Eyes may show pseudohypertelorism along with flat nasal bridge. Due to macroglossia, mouth may remain slightly open. Detailed examination may show bradycardia, hypotonia and delay in reflexes. Skin shows circulatory compromise and may show mottling or feel cold to touch . There is a higher risk of congenital malformations associated with congenital hypothyroidism. Among these cardiac malformations are the most commonly seen . Decreased activity, difficulty in feeding, constipation or hypotonia are the other common symptoms and signs seen in congenital hypothyroidism .
Entire Body System
Clinically, physical manifestations of goiter can result if left untreated. [ncbi.nlm.nih.gov]
(acquired) E03.8 Other specified hypothyroidism E03.9 Hypothyroidism, unspecified E04 Other nontoxic goiter E04.0 Nontoxic diffuse goiter E04.1 Nontoxic single thyroid nodule E04.2 Nontoxic multinodular goiter Reimbursement claims with a date of service [icd10data.com]
- Developmental Delay
A 3-year-old girl had global developmental delay with dysmorphic facies. In addition, she was found to have congenital hypothyroidism. In view of the associated dysmorphism, a karyotype analysis was done. [ncbi.nlm.nih.gov]
- Coarse Facial Features
The symptoms of congenital hypothyroidism may include the following: Puffy face Coarse facial features Dull look Thick protruding tongue Poor feeding Choking episodes Constipation or reduced stooling Yellow skin color— jaundice Short stature Swollen abdomen [health.cvs.com]
Two infants who have coarse facial features and growth and developmental delay. Pediatrics in Review, 24, 16–21. PubMed CrossRef Google Scholar Biebermann, H., Liesenkotter, K. P., Emeis, M., et al. (1999). [link.springer.com]
facial features Thick protruding tongue Goiter or enlarged thyroid Widely positioned skull bones Reduced stools or constipation Swollen hands, genitals and feet Infrequent crying or a hoarse cry Poor weight gain caused by poor appetite Birth defects, [hxbenefit.com]
Eventually, the infant may develop dry, cool, mottled skin, coarse facial features (such as a flat, broad nasal bridge and a puffy face), and a slightly open mouth with an enlarged tongue. [merckmanuals.com]
Note the hypotonic posture, coarse facial features, and umbilical hernia. The term endemic cretinism is used to describe clusters of infants with goiter and hypothyroidism in a defined geographic area. [emedicine.medscape.com]
When signs and symptoms are present, the most common include a history of prolonged gestation, large posterior and / or anterior fontanelles, puffy myxedematous faces, a large protruding tongue, hoarse cry, hypothermia, lethargy, prolonged jaundice, delayed [health.utah.gov]
Sluggish feeding Constipation Lethargic Sleep more, needs to be awakened to feed Hoarse cry Hypothermia Cardiomegaly Murmur Asymptomatic pericardial effusion Macrocytic anemia Hypotonic with slow reflexes Prolonged physiological [slideshare.net]
Examination may show macroglossia, cold or mottled skin, hypothermia, edema, wide fontanel, open sutures, flat nasal bridge, protuberant abdomen, umbilical hernia, delayed reflexes, and hypotonia. Presence of goiter indicates DH. [dovepress.com]
Initial T4 30 nmol/L % with feature Group 2 (n 232) Initial T4 30 nmol/L % with feature Prolonged Jaundice 59 33** Feeding Difficulty 35 16** Lethargy 34 14** Umbilical Hernia 32 18* Macroglossia 25 12* Constipation 18 10 Cold or mottled skin 18 10 Hypothermia [ncbi.nlm.nih.gov]
- Dysmorphic Face
Rubinstein-Taybi syndrome (RSTS), a genetic disorder characterized by growth retardation, mental deficiency, dysmorphic face, broad thumbs and large toes, generally affects monozygotic twins concordantly. [ncbi.nlm.nih.gov]
- Failure to Thrive
[…] to thrive Illustration by Emily Roberts, Verywell Causes There are two main forms of congenital hypothyroidism: permanent congenital hypothyroidism and transient congenital hypothyroidism. [thyroid.about.com]
[…] to thrive Diagnosis of Hypothyroidism Your child's doctor at Riley at IU Health can use the following exams or tests to diagnose hypothyroidism: Physical exam. [rileychildrens.org]
Jaw & Teeth
Coarse facies, macroglossia, constipation, and short trunk may become evident either during or beyond the neonatal period. These features may be subtle or may not be present at all. [currentpediatrics.com]
Common clinical features include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and [orpha.net]
There is dwarfism, macroglossia and mental dullness. iatrogenic hypothyroidism may follow treatment for hyperparathyroidism in cats. juvenile hypothyroidism congenital hypothyroidism (above). primary hypothyroidism that resulting from disease of the thyroid [medical-dictionary.thefreedictionary.com]
If fetal deficiency was severe because of complete absence (athyreosis) of the gland, physical features may include a larger anterior fontanel, persistence of a posterior fontanel, an umbilical hernia, and a large tongue (macroglossia). [en.wikipedia.org]
Symptoms Feeding difficulties Somnolence Lethargy Low frequency of crying Constipation Signs Large fontanelles Myxoedema - with coarse features and a large head and oedema of the genitalia and extremities Nasal obstruction Macroglossia Low temperature [patient.info]
Liver, Gall & Pancreas
- Neonatal Jaundice
CASE DESCRIPTION: A female infant presenting with prolonged neonatal jaundice was found to have isolated CCH, with TSH of 2.2 mU/L (Reference range, 0.4-3.5) and free T4 of 7.9 pmol/L (0.61 ng/dL) (Reference range, 10.7-21.8 pmol/L). [ncbi.nlm.nih.gov]
jaundice ( P55, P57 - P59 ) newborn P59.9 ICD-10-CM Diagnosis Code P59.9 Neonatal jaundice, unspecified 2016 2017 2018 2019 Billable/Specific Code Code on Newborn Record Applicable To Neonatal physiological jaundice (intense)(prolonged) NOS due to or [icd10data.com]
One of the first signs is prolonged neonatal jaundice (22,23) (B). [scielo.br]
- Slow Pulse
pulse Hearing loss Poor growth Poor feeding Sluggishness Short stature Lower hairline Slower heart rate Choking episodes Cool and pale skin Difficult breathing Wide, short hands Reduced activities Dry and brittle hair Swelling around eyes Coarse facial [hxbenefit.com]
pulse Weight gain (modest, no more than 5-10 lbs) The symptoms of hypothyroidism may resemble other conditions or medical problems. [stanfordchildrens.org]
- Skeletal Dysplasia
The differential diagnoses of CH include isolating its symptoms from those of disorders such as: Goiter Biliary atresia Hypopituitarism Down syndrome Iodine Deficiency Pituitary dwarfism Skeletal dysplasia Panhypopituitarism Hyperthyrotropinemia Metabolic [hxbenefit.com]
Slow linear growth, a large head with immature body proportions, and radiological features of epiphyseal dysgenesis may be mistaken for a skeletal dysplasia or pituitary dwarfism. [ncbi.nlm.nih.gov]
- Dry, Brittle Hair
brittle hair; low hairline Poor muscle tone Cool and pale skin Poor weight gain due to poor appetite Poor growth Difficult breathing Low temperature Swollen hands, feet and genitals At birth, most infants are screened for this condition. [health.cvs.com]
The child may also have: Poor feeding, choking episodes Constipation Dry, brittle hair Hoarse cry Jaundice (skin and whites of the eyes look yellow) Lack of muscle tone ( floppy infant) Low hairline Short height Sleepiness Sluggishness Exams and Tests [mountsinai.org]
The child may also have: Poor feeding, choking episodes Constipation Dry, brittle hair Hoarse cry Jaundice (skin and whites of the eyes look yellow) Lack of muscle tone ( floppy infant) Low hairline Short height Sleepiness Sluggishness A physical exam [nlm.nih.gov]
Face, Head & Neck
- Cognitive Impairment
Untreated congenital hypothyroidism can result in cognitive impairment and growth complications (decreased height/length). Initial newborn screening for congenital hypothyroidism is typically performed 24-48 hours after birth. [ncbi.nlm.nih.gov]
Principles of management Early detection and prompt initiation of thyroxine replacement can prevent severe cognitive impairment and growth failure. Affected infants require close monitoring over the first 2 years of life to maintain euthyroidism. [starship.org.nz]
impairment of the offspring. 6, 15 – 19 In this report, attention is focused on the problem of CH alone; identification and treatment of maternal hypothyroidism has been the subject of several recent reviews. 20, 21 Pilot screening programs for CH were [pediatrics.aappublications.org]
Diagnosis of CH is made by demonstrating elevated levels of TSH and decreased levels of total or free T4. Presence of neonatal and maternal antithyroid antibodies are useful in confirming the diagnosis in cases where hypothyroidism is suspected due to the presence of maternal antibodies . These antibodies from an uncommon cause of congenital hypothyroidism . Thyroid binding globulin deficiency is suspected when serum TSH levels are in the normal range, but T4 show low or low-normal serum levels. Cause of hypothyroidism can be well defined by a thyroid scan using iodine-123 or technetium-99m. It can help in differentiating congenital hypothyroidism from transient hyperthyrotropinemia  .
Diagnosis may further be made by ultrasonography done alone or in addition to scintigraphy. However, some ectopic glands may not be visible during ultrasonography . Countries where there is no or mild iodine deficiency, neonatal screening for hypothyroidism using TSH levels has proven to be helpful. However, in countries with moderate to severe iodine deficiency, this screening method doesn't have much role in view of insufficient resources to deal with the problem. Also, in these countries focus should be made towards dealing with the iodine requirements of the population. Neonatal screening, at the earliest should be done by the 5th day of life . It includes measuring TSH or blood spot T4 levels. Confirmation of diagnosis is made by elevated serum TSH levels .
- Delayed Bone Age
On diagnosis, his height was -7.5 SDs with a very delayed bone age of -13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. [ncbi.nlm.nih.gov]
Infants with delayed bone age at the time of diagnosis or in whom thyroid hormone levels take longer to return to normal values have a poor outcome. [symptoma.com]
Among the cohort with poor compliance to therapy only 33 (61.1%) patients had normal height for age and 21 (38.9%) patients height were less than 2 SD height for age associated with delayed bone age. [journals.plos.org]
The best way to control symptoms and treat congenital hypothyroidism is early detection and prompt thyroid hormone replacement. Optimal care can be achieved by diagnosing the condition early before 10-13 days of life and hence to bring the thyroid hormone levels to normal by the age of 3 weeks  . Levothyroxine is the only drug recommended for the treatment . It has been proven to be clinically safe, effective, affordable, easy to administer in pediatric age group and can be monitored with ease.
Normal growth and height development can possibly be achieved in children diagnosed with congenital hypothyroidism as long as thyroid hormone (TH) replacement therapy is persistently administered.
The introduction of TH replacement therapy by the age of 2 weeks of life is important to achieve the best possible outcome. Early start of therapy at doses of 9.5 μg/kg or more per day helps to achieve better results than that with lower doses started later . The infants with congenital hypothyroidism who are not detected early in life by newborn screening have less certainty in the prognosis of mental and neurological performances. Residual defects in infants with CH include selective memory and sensorimotor defects with impairment of visuospatial processing. The stature remains normal and physical recovery is good when replacement therapy is started within first 2 months of life . Whereas, those with intrauterine hypothyroidism and severe hypothyroidism may have low to normal IQ .
The most serious effect of untreated congenital hypothyroidism is severe mental retardation. Bone maturation and linear growth are also impaired. Neurological problems may be seen in infants in whom treatment starts with a delay. They may suffer from gait abnormalities, spasticity, mutism, dysarthria, and austistic behavior.
Early diagnosis and treatment of congenital hypothyroidism is necessary to prevent development of neurological complications and severe mental retardation . Children who are started on early treatment may still show some signs of delay in certain development areas such as reading comprehension. Irrespective of early diagnoses of CH by newborn screening, the affected children do not perform as good as those with normal thyroid functions . Infants with delayed bone age at the time of diagnosis or in whom thyroid hormone levels take longer to return to normal values have a poor outcome. IQ level in treated patients may show progressive improvement through adolescence, however, there are some cognitive problems such as those in language, memory, attention, visuospatial and fine motor function may continue to persist.
Endemic cases of cretinism are caused by insufficient iodine intake, and occasional exacerbations are brought about by goitrogens that are present naturally . The causes for congenital hypothyroidism (CH) include dysgenesis or malformation, agenesis or complete absence, and ectopy of the thyroid gland in which the thyroid gland is present lingually or sublingually. Inborn abnormalities in thyroid hormone metabolism may also occur which include dyshormonogenesis. Most cases of CH are familial in distribution and are passed as an autosomal recessive trait. Resistance to thyroid hormone as occurring in thyroid hormone receptor abnormalities is also a known cause of CH .
In cases of autoimmune conditions in the mother, the passage of autoantibodies through the placenta can cause CH that may be either transient or permanent  . Permanent congenital hypothyroidism can occur in pregnant women exposed to radioactive iodine therapy. Exposure to the iodine in contrast solutions and skin disinfectants has also been related to the development of hyperthyrotropinemia or hypothyroidism in preterm neonates . There were also findings that CH can be caused by thyroid-stimulating hormone (TSH) or thyrotropin-releasing hormone (TRH) deficiencies. TSH or TRH deficiency-related hypothroidism may occur in neonates either as an isolated finding or in the presence of other pituitary conditions such as hypopituitarism.
The causes of permanent congenital hypothyroidism can either be classified into primary or secondary (central). The causes that fall under primary category include abnormalities in the thyroid gland development, production of insufficient thyroid hormones, and defective TSH binding or signal transduction. Peripheral hypothyroidism can be caused by defective thyroid hormone metabolism, transport or resistance to thyroid hormone. Defective binding or formation of thyrotropin releasing hormone (TRH) and TSH production are the causes resulting in secondary or central hypothyroidism.
Presently, the incidence of congenital hypothyroidism is approximately 1 in 2,000 up to 1 in 4,000 newborns. It was in the range of 1:7,000 to 1:10,000 before the introduction of newborn screening programs and diagnosis was made by clinical manifestations . Initially, when the screening of newborns was introduced, the incidence was between 1:3,000 to 1:4,000 .
T4 is the main hormone that is produced by the thyroid gland. Only 10 to 40% of the circulating T3 is released by the thyroid gland. Rest of T3 is produced in peripheral tissue by the process of monodeiodination of T4. The biological effects of thyroid hormones are mainly produced by T3 and it acts via specific nuclear receptors. Any abnormality in receptors can result in resistance to thyroid hormones. There are certain proteins which act as carriers to circulating thyroid hormones, these are thyroid-binding globulin (TBG), albumin and thyroid-binding prealbumin (TBPA).
Only the free and unbound form of T4 is metabolically active and constitutes around 0.03% of circulating T4. Infants with congenital TBG deficiency have low levels of TBG andT4 but are physiologically normal. A familial congenital form of TBG deficiency can occur as autosomal recessive or X-linked recessive condition.
The maternal disease of the thyroid gland can have a greater influence on fetal and neonatal thyroid function. Maternal thyroid hormone levels may also show some mild influence on the fetus. In autoimmune thyroiditis, IgG autoantibodies can inhibit thyroid functions by crossing the placenta. Fetal thyroid hormone synthesis can also be blocked by thioamides used in the treatment of maternal hyperthyroidism. However, most of these defects are transient. Pregnant women exposed to radioactive iodine can show permanent ablation of fetal thyroid gland. Thyroid hormone is important for the normal growth and myelination of the brain and formation of normal neuronal connections. Comparison of children treated and untreated for congenital hypothyroidism has demonstrated the importance of thyroid hormone in brain growth and development.
Congenital hypothyroidism cannot be prevented, However, steps can be taken to maintain the normal levels of thyroid hormones on hormone supplementation and prevent the development of associated sequelae.
In iodine-deficient areas, dietary supplementation of iodine helps prevent endemic cretinism. However, it doesn't have much role in the prevention of sporadic congenital hypothyroidism. Worldwide, the most common cause of brain damage is a dietary iodine deficiency which is easily preventable . In the infants with congenital hypothyroidism soy-based formulas can decrease the absorption of levothyroxine , however, it is not a contraindication for its use. If an infant is switched to soy-based from mild-based formula, dose of thyroid hormone needs to be increased to maintain the normal thyroid function .
Supplementation with iodine can prevent the development of cretinism and endemic goiter, but fails in cases of congenital hypothyroidism. Early diagnosis of congenital hypothyroidism open link by newborn screening programs can be made as early as 3 weeks of life. Management with adequate and early treatment can help prevent and decrease in the development of sequelae in many.
Congenital hypothyroidism (CH) is among the most common, and easily preventable causes of mental retardation. In the majority of cases, the condition becomes permanent throughout life as a result of abnormal development of the thyroid gland or defect in the formation of the thyroid hormones. Rare conditions that involve the presence of maternal blocking antibodies, transplacental absorption of maternal medications, and excessive or deficient iodine can lead to alteration of neonatal thyroid function. In less common cases, pituitary or hypothalamic abnormalities (tertiary/secondary or central hypopituitarism) may also lead to congenital hypothyroidism.
Congenital hypothyroidism (CH) is one of the causes of mental retardation. But, is also among the common preventable one. Screening of newborn at early life is helpful in detection of CH at the initial stages. Babies with congenital hypothyroidism have hoarse cry and suffer from constipation. They are usually calm and quiet and don't wake much during night sleep. It is possible to achieve normal neurodevelopment by early diagnosis of the condition and initiation of the treatment in the form of thyroid hormone supplementation.
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