Congenital+Hypothyroidism

=Congenital Hypothyroidism=

What it is
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.

By the end of the first trimester, the thyroid gland is not only located in its normal location in the neck, but it is also capable of collecting iodine and other raw materials from the fetal circulation for the production of thyroid hormone.

During the time that the thyroid gland develops, the hypothalamus and pituitary also develop. Early in the second trimester, the hypothalamus specifically begins to signal the pituitary to produce and release a messenger hormone known as thyroid-stimulating hormone (TSH) into the fetal blood stream. Through the second trimester, TSH levels rise in the fetal blood, and, as a result, stimulate the thyroid gland to grow properly and to begin to produce thyroid hormone. In a manner that resembles an assembly line process, thyroid gland cells take iodine and other raw materials (e.g., amino acids) from the fetal blood stream and convert them, through a series of enzymatic reaction steps, into thyroid hormone. Thyroid hormone is made as part of a very large protein called thyroglobulin which is stored inside the thyroid gland. Through another series of enzymatic reaction steps, thyroid hormone is cut from the large thyroglobulin molecule and released into the blood stream.

Through the second and the third trimesters, the complex mechanisms that regulate the hormonal interactions between the hypothalamus, pituitary, and thyroid gland gradually mature. As these mechanisms mature, the thyroid gland system becomes more and more finely tuned to produce and release just the right amounts of thyroid hormone into the developing baby's blood stream. By the time the baby reaches full term, the thyroid gland system is entirely functional and ready to provide all the newborn baby's requirements for thyroid hormone. The continuous maintenance of proper thyroid hormone levels from the newborn period through childhood is absolutely essential for normal postnatal physical growth and brain development.

Each year in South Australia, approximately 8 babies are born with Congenital Hypothyroidism The term endemic cretinism is used to describe clusters of infants with goiter and cretinism in defined geographic areas. These areas were discovered to be low in iodine, and the cause of endemic cretinism was determined to be iodine deficiency.
 * Risk Factors**

Congenital hypothyroidism is observed in all populations. The racial differences observed in endemic cretinism are probably related more to geographic location and socioeconomic status than to any particular racial predilection.

Twin births are approximately 12 times as likely to have congenital hypothyroidism as singletons.

Most studies of congenital hypothyroidism suggest a female-to-male ratio of a 2:1. In 1999, Devos et al showed that much of the discrepancy is accounted for by infants with thyroid ectopy.

Congenital hypothyroidism is more common in infants with birthweights less than 2,000 g or more than 4,500 g.

During the early months of pregnancy, when your baby’s organs are developing, the thyroid gland moves from the back of the tongue to its normal position in the neck. In some babies this does not happen, which means that the gland cannot work properly. On other occasions the thyroid gland does not develop at all. If you have one child with this type of congenital hypothyroidism, the chance of having another baby who is affected is very low. There is another very rare type of hypothyroidism in which a child’s thyroid gland is in the right place, but it cannot produce thyroxine. This type is inherited and so there is a risk that if you have another child in the future they may have the same condition. If you are worried, please ask to talk to a genetics nurse about this.
 * Cause**

Endemic cretinism is caused by iodine deficiency and is occasionally exacerbated by naturally occurring goitrogens.

Congenital hypothyroidism can be caused by any of the following:

Permanent types of congenital hypothyroidism can be separated into the following 3 categories: In this category, the thyroid gland is either absent, markedly under-developed, or not in its proper location. About 80-85% of babies with CH fall into this category. The exact cause of these disorders remains unknown. They occur sporadically, which means they are not inherited disorders. In addition, there is no evidence right now to suggest that either parent did, or failed to do, something to cause the CH to occur. The likelihood of two parents having more than one baby affected with this type of CH is only slightly higher than the original 1 in 4000 chance. In this category, there is either a deficiency of or an abnormality in one of the many enzymatic reaction steps involved in thyroid hormone production or release. About 10-15% of babies with CH fall into this category. The majority of these conditions are inherited as autosomal recessive disorders. This means that the affected child inherited the genes for CH from both the mother and the father. Therefore, the chance that CH will occur again in the family remains at 1 in 4 for each and every child born. In this category, the thyroid gland forms and descends properly, but the messenger hormone TSH is either not produced or released properly from the pituitary gland. As a result, the thyroid gland does not receive the TSH signal that is required for the normal production and release of thyroid hormone. Less than 5% of babies with CH are in this category. There are a variety of very uncommon medical conditions associated with central hypothyroidism. Some of these occur sporadically, while some are inherited disorders. In addition, TSH deficiency can occur either by itself or in association with other pituitary gland hormone deficiencies or brain abnormalities.
 * Dysgenesis of the thyroid gland
 * Agenesis (ie, complete absence of thyroid gland)
 * Ectopy (lingual or sublingual thyroid gland)
 * Inborn errors of thyroid hormone metabolism - Dyshormonogenesis (most cases are familial and inherited as autosomal recessive conditions)
 * TSH unresponsiveness (ie, TSH receptor abnormalities)
 * 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)
 * Maternal autoimmune disease (transient or permanent)
 * Iatrogenic causes - Maternal use of thioamides, iodine excess, radioactive iodine therapy
 * TSH or thyrotropin-releasing hormone (TRH) deficiencies
 * 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.
 * 1. Abnormalities of formation, migration, and growth of the thyroid gland** //(referred to as thyroid dysgenesis)//
 * 2. Abnormalities of enzymatic reaction steps involved in thyroid hormone production or release** //(referred to as thyroid dyshormonogenesis)//
 * 3. Abnormalities of the formation or function of the hypothalamus and/or pituitary** //(referred to as central hypothyroidism)//

Symptoms
Symptoms and signs include the following: Signs include the following: When the body is deprived of thyroid hormone, the pituitary gland works overtime, producing extra thyroid-stimulating hormone (TSH). This glut of TSH may enlarge the thyroid into a condition called a goiter.
 * Decreased activity
 * Large anterior fontanelle
 * Poor feeding and weight gain
 * Small stature or poor growth
 * Jaundice (due to impaired bilirubin conjugation - commonly experienced in newborn babies for a week or two, but in untreated hypothyroidism it can least for much longer)
 * Decreased stooling or constipation
 * Hypotonia
 * Hoarse cry
 * Coarse facial features
 * Macroglossia
 * Large fontanelles
 * Umbilical hernia
 * Mottled, cool, and dry skin
 * Developmental delay / mental retardation
 * Pallor
 * Myxedema
 * Goiter

From a physician's standpoint, CH can be extremely difficult to diagnose in a baby soon after birth. Even though there are "classic symptoms and signs" (e.g., prolonged jaundice, enlarged soft spots, umbilical hernia, poor feeding, constipation, cool or mottled skin, increased sleepiness, decreased crying, etc.) associated with CH, in the majority (~95%) of babies with CH, these findings are often very subtle and tend to go either undetected or unappreciated during the first few weeks of life. In fact, most parents are surprised to learn that their baby has CH, and many will tend to describe their infants as "good babies that rarely cry, aren't demanding, and tend to sleep during the day and night."

How to Treat
All babies in Australia are screened for Congenital Hypothyroidism. This screening began in South Australia in 1977. About two days after birth, a small amount of blood is taken from the baby’s heel, placed on a piece of filter paper and forwarded to a central laboratory for assay. Babies with all four categories of Congenital Hypothyroidism will be identified because they will have high levels of thyroid stimulating hormone. Babies who have hypothyroidism as part of a pituitary gland problem will have low or undetectable levels of TSH and will NOT be identified by the Screening Program. The reason why Newborn Screening is carried out are as follows:
 * Diagnosis**

1. It is very difficult to diagnose Congenital Hypothyroidism at birth, just by examining the baby. Some of the features described previously e.g. slow growth and impaired mental development are not present at birth. They take some time, months in fact, to develop. Therefore, if Newborn Screening is not carried out, most cases of hypothyroidism will be missed at birth and treatment delayed. \

2. Congenital hypothyroidism is a relatively common condition. About 8 new cases are diagnosed in South Australia each year (one in 3,500 births).

3. With early diagnosis and treatment, it can be confidently expected that even severely affected infants will develop normally both physically and mentally. The other investigation that is performed at this time is called a thyroid scan. For this test, the baby is given an injection of a radioactive substance called technetium which is taken up by the thyroid gland. Thus it is possible to see the position and shape of the thyroid and see if the gland is absent, ectopic or present in the normal position. There is virtually no risk associated with the use of technetium because only a low dose is used and its radioactivity goes away within hours. A thyroid scan can only be performed when the baby is not on treatment. This is why it is usually done at the first visit.

In hypothyroidism, the thyroid gland is unable to make enough thyroxine for the body’s needs, and therefore this hormone must be replaced. It is given in tablet form by mouth. The thyroxine that is present in the tablets is exactly the same as the thyroxine that is naturally present in the body. Thyroxine is now made by chemical means, previously it was extracted from the thyroid glands of animals. The amount of thyroxine that is given depends upon a number of factors, including the size of the patient. Naturally, as the baby grows, a bigger dose will be needed. Once treatment has been started, blood tests are done at regular intervals in order to measure the concentration of the thyroid hormone in the blood. These tests are usually done every three months for the first three years of life, four monthly till age seven then six monthly thereafter. We aim to keep the thyroxine level in the blood about the upper limit of normal. With appropriate treatment, the stimulus to the pituitary gland to secrete large amounts of thyroid stimulating hormone will no longer be present. Therefore, the level of this hormone in the blood will be suppressed, but it may take If treatment is inadequate, e.g. if the dosage is too low or the tablets are not being given properly, the thyroxine concentration in the blood will be low and there will be an elevated level of the thyroid stimulating hormone. The baby or child may be drowsy or tired. Treatment for permanent hypothyroidism is life-long. If the tablets are ceased for a prolonged time, the symptoms already described will return.
 * Treatment**

Other advice
It is difficult to predict whether any young child will grow up normally. However, screening for congenital hypothyroidism has been happening for long enough for us to know that almost all children who are diagnosed and treated from an early age will grow up normally. However, a small proportion of children who have had severe hypothyroidism in the womb may have some difficulties later in life, like poor hearing, clumsiness or trouble with learning. These problems can be reduced if hypothyroidism is picked up early and treated as described above.

Additional Resources
[|eMedicine - Overview] [|WCH - An information guide for parents] [|Learn.Genetics - Hypothyroidism] [|NHS - Congenital Hypothyroidism] [|Thyroid Australia - Congenital Hypothyroidism]