Congenital Hypothyroidism

What is Congenital Hypothyroidism?

Congenital hypothyroidism (CH) is a disorder characterized by thyroid hormone deficiency that is present at birth. A complete or partial loss of thyroid functions occurs in a newborn due to a myriad of reasons. This leads to disturbances in growth, metabolism and brain development. If left untreated, CH can give rise to abnormal growth and severe intellectual disability.

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CH is also known by certain other names, such as:

  • CHT
  • Cretinism
  • Congenital Myxedema
  • Endemic Cretinism (iodine deficiency)

Congenital Hypothyroidism Epidemiology

CH is a rare disorder, occurring in almost 1 in every 3000 to 4000 individuals. Although the condition has been observed in all populations throughout the world, it is slightly more prevalent among the Hispanic group. Girls are twice as much affected by CH as boys.

Congenital Hypothyroidism Causes

CH can be caused by a number of underlying factors, which are discussed below:

Misplaced or missing thyroid gland

Most infants born with CH either have a thyroid gland that fails to develop properly or is missing altogether. In certain cases, the gland might be smaller in size than usual or not located in its proper place.

In healthy individuals, the thyroid gland is placed at the center of the front part of the neck, close to the top of the windpipe. In some newborns having CH, the gland might instead be placed at the side of neck or under the tongue. An underdeveloped or misplaced thyroid gland often fails to work at their optimal level and produce less thyroid hormone than what is required by the body. In case the thyroid gland is absent, a baby cannot produce any of his or her own thyroid hormone. A misplaced (ectopic), underdeveloped (hypoplastic) or missing (athyreosis) thyroid gland is a type of birth defect that is caused by unknown factors and is generally not inherited.

Hereditary factors

In some lesser known cases, CH develops due to inherited changes within a single gene or a pair of genes. Children with inherited type of congenital hypothyroidism do not make sufficient quantities of thyroid hormone in spite of the fact that their thyroid gland seems to be normal in shape and size. Around 15% of children born with CH are believed to have the inherited form of the disorder.

Genetic factors

CH can also develop due to the genetic defects of triiodothyronine or thyroxine synthesis occurring within a structurally healthy thyroid gland. The specific defects include:

  • Organification defect
  • Iodine trapping defect
  • Thyroglobulin deficiency
  • Thyrotropin (TSH) resistance
  • Iodotyrosine deiodinase deficiency

In some cases of CH, the defect is caused by a deficiency of the thyroid stimulating hormone (TSH), either in isolation or as a part of the congenital hypopituitarism. The genetic types of non-goitrous congenital hypothyroidism include:

  • CHNG1
  • CHNG2
  • CHNG3
  • CHNG4
  • CHNG5

Maternal iodine deficiency

The fetal thyroid gland fails to make sufficient amounts of thyroid hormone if the mother is having an iodine deficiency during her pregnancy. In such cases, the baby is born with congenital hypothyroidism. This is a major problem in certain areas of the world where the people fail to get enough quantities of iodine in their regular diet. However, CH in United States and other developed countries rarely occurs due to this factor as the table salt in these places is supplemented with iodine, i.e., iodized salt. Other foods such as dairy products also have sufficient quantities of iodine.

Maternal thyroid conditions and medications

In some rare cases, CH develops when a mother is treated with anti-thyroid drugs during her pregnancy to manage her own thyroid problems.

Apart from the above mentioned causes, CH may also occur sporadically due to some idiopathic factors.

Congenital Hypothyroidism Symptoms

Infants born with CH may show no definite, recognizable signs or may display certain mild effects that frequently go unrecognized as any major issue. The common signs that can be observed initially include:

  • Excessive sleeping
  • Low or a hoarse cry
  • Exaggerated jaundice
  • Lower body temperature
  • Infrequent bowel movements
  • Reduced interest in feeding or nursing
  • Poor muscle tone, i.e. a floppy infant (hypotonia)

In case of severe fetal deficiency due to a complete absence or athyreosis of the thyroid gland, the affected infants may present with physical features such as:

  • An umbilical hernia
  • Larger anterior fontanel
  • A large tongue or macroglossia
  • Persistence of a posterior fontanel

Other common features associated with this disorder include:

  • Anemia
  • Dull look
  • Puffy face
  • Slow 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 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, such as heart valve abnormalities
  • Buildup of fluids under the skin, known as myxedema
  • Swollen or protuberant belly button, i.e. umbilical hernia
  • Delayed developmental milestones (crawling, sitting, walking, talking)
  • Large soft spot present on the skull, i.e. the fontanel that has a late closure

Children who are left untreated generally become mentally retarded and have a much shorter height than average. Spasticity and unsteady gait are also common features. Many have speech delays as well as some other behavior problems.

Congenital Hypothyroidism Diagnosis

In the developed countries, almost all instances of CH are detected by a newborn screening program which is based on measurements of thyroxine (T4) or TSH on the 2nd or 3rd day of life. A high TSH or low T4 needs to be followed up quickly by immediate treatment that is supervised by a pediatric endocrinologist. A technetium or Tc-99m pertechnetate thyroid scan can help to identify a structurally abnormal thyroid gland. Other diagnostic tests that may be done to detect CH include:

  • Scintigraphy
  • X-rays of long bones
  • Anti-thyroid antibodies
  • Evaluation of TBG levels
  • Thyroid ultrasonography
  • Urinary iodine determination
  • Thyroid radionuclide uptake and scan
  • Serum thyroglobulin (Tg) determination
  • Radioactive iodine (RAIU) exam; this test helps to differentiate congenital absence and defects in organification (a fundamental process necessary to produce thyroid hormones)

Genetic mutations

Genetic testing should be conducted to detect the following genetic disorders:

  • TSH receptor inactivating mutations
  • TSHβ mutations
  • Thyroid dysgenesis
    • TTF-2 mutations
    • PAX-8 mutations
    • NKX2.1 mutations
    • Thyroid dyshormonegenesis
      • Hydrogen peroxide mutations
        • DUOX2A mutations
        • DUOX2 mutations
  • Sodium-iodide symporter mutations
  • Thyroid peroxidase mutations
    • Pendred syndrome (PDS): pendrin gene mutations
  • Deiodinase mutations
  • Thyroglobulin mutations
  • Defects in thyroid hormone transport
    • MCT8 mutation

Congenital Hypothyroidism Screening

There are 3 screening strategies that are commonly in use for detecting CH. These are:

  • Primary measurement of TSH with backup T4 (thyroxine) determination in the infants having high TSH levels;
  • Primary T4 measurement carried out with backup TSH evaluation done in infants having low T4 (thyroxine) levels; and
  • Simultaneous measurement of TSH and T4 levels

Physicians should be well alert of the limitations associated with each of these methods. Primary measurement of TSH with backup T4 (thyroxine) assessment misses the delayed TSH elevation occurring in infants having TBG (thyroxine-binding globulin) deficiency, hypothyroxinemia or central hypothyroidism. Along with this, the normal postnatal increasing in the TSH levels can pose as an issue when the affected infants are discharged earlier.

Primary T4 measurement carried out with backup TSH evaluation can detect:

  • Primary hypothyroidism
  • Central hypothyroidism
  • TBG deficiency
  • Hyperthyroxinemia

However, this particular method often misses hyperthyroxinemia in the infants having delayed TSH increase with initially normal T4.

The best method of screening is the simultaneous approach, although this method is not yet feasible on a regular basis.

Screening for CH should be performed on all infants between 2 and 4 days of birth. However, if this seems difficult, the testing should be conducted before being discharged or within 7 days of birth. False positive TSH elevations can be detected in specimens that are collected between 24 and 48 hours after birth. False negative results can be detected in seriously ill newborns or in the post-transfusion infants. Screening prior to the transfusion or discharge is ideally preferable to missing a diagnosis. Special attention should be given to infants kept under emergency care so as not to miss the screening.

Congenital Hypothyroidism Differential Diagnosis

The signs and symptoms of a number of health disorders overlap with that of CH. Hence, while diagnosing this condition, its signs should be differentiated from those of such similar disorders in order to establish a precise diagnosis. 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 storage disease
  • Neonatal hypothyroxinemia
  • Beckwith-Wiedemann Syndrome
  • Transient neonatal hypothyroidism
  • Thyroxine-Binding Globulin Deficiency

Congenital Hypothyroidism Treatment

CH is usually treated with thyroid hormone replacement therapy. This is a safe procedure and is easy to take. If treatment is started immediately after a child is diagnosed, it can help to prevent most or all of the side effects of CH. If delay of treatment causes damage to the brain or central nervous system and the nerves, it is generally permanent and is not possible to be reversed.


Suffering infants are treated with L-thyroxine, a synthetic variant of the thyroid hormone whose chemical structure is same as that which is produced by the thyroid gland. This can be administered as tablets to all the babies having CH. The dosage would be decided upon by a team of the doctors and endocrinologists. The amounts of the medication will be gradually increased as a child grows. L-thyroxine should be taken every day by a patient throughout life.

These small tablets can be easily crushed and mixed into food or a small quantity of juice, formula or some other liquid. It is best not to dissolve the tablets into a glass or a full bottle of liquid as the baby may not be able to finish the entire bottle and thus not get the full dosage of medicine. The pills can be easily chewed and swallowed by young children. No approved liquid variant of thyroid hormone exists.

Typically, L-thyroxine tablets should be administered at least 30 minutes before a particular meal or feeding. The dose range that is most commonly recommended is 10-15 μg/kg per day, usually 37.5 or 44 μg.

The most common brands of L-thyroxine include:

  • Levoxyl
  • Unithroid
  • Synthroid
  • Levothroid
  • Levothyroxine

The safest medication to treat CH is synthetic L-thyroxine. During the past, prior to the availability of synthetic forms, affected children were given dried thyroid hormone obtained from pooled animal tissues. This is known as dessicated thyroid and it is still available today. However, using dessicated thyroid is not advisable as the dose of the hormone present within it is not consistent.


Dietary iodide supplementation administered in iodine-deficient areas can help to prevent endemic cretinism. However, it does not have any major effect on the management of sporadic CH. Children should be given iron supplements and soy-based formulas which can decrease the overall absorption of thyroid hormone from the L-thyroxine tablets. There should be at least a one hour gap between feeding the child iron supplements or soy formula and synthetic L-thyroxine pills. The doctor who is in charge of treatment should be notified that the baby is being fed iron supplements or soy formula, so that the medications can be adjusted or monitored if necessary.


A child put under treatment with L-thyroxine should be regularly taken to the doctor for an overall checkup of his or her height, weight, development and general health. Regular blood tests should also be conducted to evaluate the levels of thyroid hormone. The blood tests are normally done every 1 to 3 months until the child is about 1 year old, and then every 2 to 4 months until about the age of 3. The frequency of blood tests can be reduced after the child reaches 3 years of age.

Developmental Evaluation

The doctor might suggest an overall evaluation of the child’s development. If the child shows delays in some specific areas of speech or learning, it might be possible to arrange for additional help. Early intervention programs can be availed which are present in most developed countries to provide support to young children before they attain school age.

Congenital Hypothyroidism Complications

Children born with CH can suffer from the following complications:

  • Mutism
  • Spasticity
  • Dysarthria
  • Heart problems
  • Autistic behavior
  • Gait abnormalities
  • Visuospatial problems
  • Mental retardation and intellectual disability
  • Severe impairment of bone maturation and linear growth

Congenital Hypothyroidism Prognosis

Most infants born with CH who are treated correctly with thyroxine are likely to develop and grow normally in every respect. Even most patients with athyreosis as well as undetectable T4 (thyroxine) levels at birth have shown normal intelligence, although their general academic performance is slightly lower than that of their siblings and moderate to mild learning difficulties can be seen in some individuals. Despite treatment, infants diagnosed with CH by newborn screening generally do not fare as good as their euthyroid counterparts. Early treatment can help to minimize cognitive difficulties as well as avoid further complications associated with this disorder.

CH is the most commonly preventable cause of intellectual disability and mental retardation. An early detection, followed by appropriate treatment, leads to a better outcome.

Congenital Hypothyroidism Prevention

Although dietary iodide supplementation helps to prevent cretinism and endemic goiter, it does not assist in protecting the child from sporadic CH. Long-acting intramuscular shots of iodized oil as well as oral lipiodol has also been proven effective to manage hypothyroidism in some areas. Mothers should not be treated with radioactive iodine or have iodine as an antiseptic. Various methods of prenatal screening and diagnosis are currently being evaluated.

Congenital Hypothyroidism Pictures

Here are some images showing the physical appearance of infants born with CH.

Picture 1 – Congenital Hypothyroidism Image Source via Wikimedia Commons


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