INTRODUCTION 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 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. In the 1930s, adequate dietary intake of iodine was found to prevent this goiter and cretinism. Thus, the wholesale iodization of salt was established. Despite its efforts, the World Health Organization (WHO) has not been able to completely eliminate iodine deficiency throughout the world. As a result, 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 animal thyroid extract was found to elicit some improvement in these infants, although many remained impaired.

The morbidity from congenital hypothyroidism can be reduced to a minimum by early diagnosis and treatment, which was made feasible by the development of radioimmunoassay for thyroidstimulating hormone (TSH) and thyroxine (T4) from blood spots on filter paper, obtained for neonatal screening tests.
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CHAPTER 1 Congenital Hypothyroidism

Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency present at birth. Approximately 1 in 4000 newborn infants has a severe deficiency of thyroid function, while even more have mild or partial degrees. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent mental retardation. Treatment consists of a daily dose of thyroid hormone (thyroxine) by mouth. Because the treatment is simple, effective, and inexpensive, nearly all of the developed world practices newborn screening to detect and treat congenital hypothyroidism in the first weeks of life.

Etiology Around the world, the most common cause of congenital hypothyroidism is iodine deficiency, but in most of the developed world and areas of adequate environmental iodine, cases are due to a combination of known and unknown causes. Most commonly there is a defect of development of the thyroid gland itself, resulting in an absent (athyreosis) or underdeveloped (hypoplastic) gland. A hypoplastic gland may develop higher in the neck or even in the back of the tongue. A gland in the wrong place is referred to as ectopic, and an ectopic gland at the base or back of the tongue is a lingual thyroid. Some of these cases of developmentally abnormal glands result from genetic defects, and some are "sporadic," with no identifiable cause. One Japanese study found a

statistical correlation between certain organochlorine insecticides and dioxin-like chemicals in the milk of mothers who had given birth to infants with congenital hypothyroidism.[1] In some instances, hypothyroidism detected by screening may be transient. The most common cause of this is the presence of maternal antibodies which temporarily impair thyroid function for several weeks. Cretinism is an old term for the state of mental and physical retardation resulting from untreated congenital hypothyroidism, usually due to iodine deficiency from birth because of low iodine levels in the soil and local food sources. The term, like so many other 19th century medical terms, acquired pejorative connotations as it became used in lay speech. It is now rarely used by physicians. Genetic Congenital hypothyroidism can also occur due to genetic defects of thyroxine or triiodothyronine synthesis within a structurally normal gland. Among specific defects are thyrotropin (TSH) resistance, iodine trapping defect, organification defect, thyroglobulin, and iodotyrosine deiodinase deficiency. In a small proportion of cases of congenital hypothyroidism, the defect is due to a deficiency of thyroid stimulating hormone, either isolated or as part of congenital hypopituitarism. Diagnostic evaluation In the developed world, nearly all cases of congenital hypothyroidism are detected by the newborn screening program. These are based on measurement of TSH or thyroxine (T4) on the second or third day of life. If the TSH is high, or the T4 low, the infant's doctor and parents are called and a referral to a pediatric endocrinologist is recommended to confirm the diagnosis and
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initiate treatment. Often a technetium (Tc-99m pertechnetate) thyroid scan is performed to detect a structurally abnormal gland. The Tc-99m pertechnetate exam will help differentiate congenital absence or a defect in organification (a process necessary to make thyroid hormone). Treatment The goal of newborn screening programs is to detect and start treatment within the first 12 weeks of life. Treatment consists of a daily dose of thyroxine, available as a small tablet. The generic name is levothyroxine, and several brands are available. Commonly used brands in North America are Synthroid, Levoxyl, Unithroid, and Levothroid. The tablet is crushed and given to the infant with a small amount of water or milk. The most commonly recommended dose range is 10-15 g/kg daily, typically 37.5 or 44 g.[3] Within a few weeks, the T4 and TSH levels are rechecked to confirm that they are being normalized by treatment. As the child grows up, these levels are checked regularly to maintain the right dose. The dose increases as the child grows. Symptoms Infants born with congenital hypothyroidism may show no effects, or may display mild effects that often go unrecognized as a problem: excessive sleeping, reduced interest in nursing, poor muscle tone, low or hoarse cry, infrequent bowel movements, exaggerated jaundice, and low body temperature. 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). In the era before newborn screening, less than half of cases of severe hypothyroidism were recognized in the first month of life. As the months proceeded, these infants would grow poorly
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and be delayed in their development. By several years of age, they would display the recognizable facial and body features of cretinism. Persistence of severe, untreated hypothyroidism resulted in severe mental impairment, with an IQ below 80 in the majority. Most of these children eventually ended up in institutional care. Prognosis Most children born with congenital hypothyroidism and correctly treated with thyroxine grow and develop normally in all respects. Even most of those with athyreosis and undetectable T4 levels at birth develop with normal intelligence, although as a population academic performance tends to be below that of siblings and mild learning problems occur in some. Congenital hypothyroidism is the most common preventable cause of mental retardation. Few treatments in the practice of medicine provide as large a benefit for as small an effort.

CHAPTER 2 An Endocrine Disorder Affecting Newborns

Congenital hypothyroidism is a rare endocrine disorder affecting approximately one in 4,000 infants. The thyroid is a small butterfly shaped gland positioned at the base of the neck that produces hormones to regulate the bodys physical and mental growth. Congenital hypothyroidism occurs when an infants thyroid gland does not produce adequate amounts of the thyroid hormone. Causes Most cases of congenital hypothyroidism occur sporadically, resulting from an error in the development of the thyroid gland. In these instances, the thyroid may have failed to develop, may have developed in the wrong location, or may have only partially formed. The error in development results in impairing the function of the thyroid stimulating hormone (TSH). Some cases of congenital hypothyroidism are attributed to inheriting autosomal recessive traits. These cases of inborn errors can affect thyroid metabolism in normally developed thyroid glands. Iodine deficiency was once a leading contributor to congenital hypothyroidism. With the widespread introduction of iodine into diets, the number of cases in developed countries attributed to iodine deficiency has been significantly reduced.

Symptoms Babies with congenital hypothyroidism may have the following symptoms

excessive sleeping; poor eating and weight gain; poor muscle tone; weak cry; constipation or irregular bowl movements; exaggerated jaundice; low body temperature; decreased activity; and/or dry skin or brittle hair.

Symptoms are often asymptomatic and can go unnoticed for a period of time. Because of this, it is imperative that the disorder is identified through a newborn screening test. Diagnose A newborn screening test is performed on infants within 24 to 72 hours after birth. This test screens for a number of disorders, including congenital hypothyroidism. Congenital hypothyroidism is detected by increased levels of TSH or decreased levels of thyroxine (T4) in the newborns blood.
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A pediatric endocrinologist will confirm the results of abnormal screens with an additional blood test. The doctor may also administer an ultrasound to determine the location and state of development of the thyroid gland. Treatment and Outcome Once the diagnosis of congenital hypothyroidism has been confirmed, lifelong treatment with thyroid hormone replacement therapy must begin immediately. The thyroid hormone replacement therapy, levothyroxine, is a synthetic version of the thyroid hormone and is available in the form of a pill. The pill is most effectively administered by placing it on the back of the infants tongue and offering the breast, bottle, or pacifier to initiate swallowing. Liquid preparations of the therapy should be avoided because of potential inconsistencies with its administration. Newborns will require monitoring of the thyroid hormones through regular blood tests. The dosage of the thyroid hormone replacement therapy is adjusted as necessary as the baby grows. The blood tests should typically be performed every two to three months until the age of three years, and more often after each change in dosage. A pediatric endocrinologist will monitor the blood test schedule and treatment.

CHAPTER 3 CONCLUSION If CH is detected early in infants and treatment begun, normal development of mental function can occur. If treatment is delayed spasticity, gait problems and dysarthria and profound mental disability may result.

Poor self-esteem and depression are amongst several factors that lead to a poorer quality of life in patients who have been treated for CH. A high index of suspicion with careful questioning is required to pick up on these aspects. The thyroid is fundamental in babies physical and mental development. If left untreated, congenital hypothyroidism can cause mental retardation and stunted physical growth. If treatment is delayed, irreversible neurological problems can occur. Fortunately, infants who are diagnosed early and begin treatment immediately can develop normally, both physically and mentally.

REFERENCES

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