Congenital hypothyroidism
Encyclopedia
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.
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.
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.
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
.
Genetic types of nongoitrous congenital hypothyroidism include:
Nongoitrous congenital hypothyroidism has been described as the "most prevalent inborn endocrine disorder".
is recommended to confirm the diagnosis and initiate treatment. Often a technetium
(Tc-99m pertechnetate) thyroid scan is performed to detect a structurally abnormal gland. A radioactive iodine (RAIU) exam will help differentiate congenital absence or a defect in organification (a process necessary to make thyroid hormone).
, 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 μg
/kg daily, typically 37.5 or 44 μg.
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.
, 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 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.
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.
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
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
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
. Treatment consists of a daily dose of thyroid hormone (thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
) by mouth. Because the treatment is simple, effective, and inexpensive, nearly all of the developed world practices newborn screening
Newborn screening
Newborn screening is the process by which infants are screened shortly after birth for a list of disorders that are treatable, but difficult or impossible to detect clinically. Screening programs are often run by state or national governing bodies with the goal of screening all infants born in the...
to detect and treat congenital hypothyroidism in the first weeks of life.
Etiology
Around the world, the most common cause of congenital hypothyroidism is iodineIodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
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.
In some instances, hypothyroidism detected by screening may be transient. The most common cause of this is the presence of maternal antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
which temporarily impair thyroid function for several weeks.
Cretinism
Cretinism
Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones usually due to maternal hypothyroidism.-Etymology and use of cretin:...
is an old term for the state of mental and physical retardation resulting from untreated congenital hypothyroidism, usually due to iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
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 triiodothyronineTriiodothyronine
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate....
synthesis within a structurally normal gland. Among specific defects are thyrotropin (TSH
TSH
TSH may refer to:* Tanzanian shilling, the currency of Tanzania* Thyroid-stimulating hormone, a hormone synthesized and secreted by thyrotrope cells* Tshiuetin Rail Transportation, a Canadian railway between Labrador and Quebec...
) resistance, iodine trapping defect, organification defect, thyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....
, and iodotyrosine deiodinase
Iodotyrosine deiodinase
Iodotyrosine deiodinase also known as iodotyrosine dehalogenase 1 is an enzyme that in humans is encoded by the IYD gene.- Function :...
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
Hypopituitarism
Hypopituitarism is the decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain...
.
Genetic types of nongoitrous congenital hypothyroidism include:
| OMIM | Name | Gene |
|---|---|---|
| congenital hypothyroidism, nongoitrous 1 CHNG1 | TSHR | |
| CHNG2 | PAX8 PAX8 Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the PAX8 gene.- Function :This gene is a member of the paired box family of transcription factors. Members of this gene family typically encode proteins which contain a paired box domain, an octapeptide, and a... |
|
| CHNG3 | ? at 15q25.3-q26.1 | |
| CHNG4 | TSHB TSHB Thyroid stimulating hormone, beta also known as TSHB is a protein which in humans is encoded by the TSHB gene.- Function :Thyrotropin-stimulating hormone is a noncovalently linked glycoprotein heterodimer and is part of a family of pituitary hormones containing a common alpha subunit and a unique... |
|
| CHNG5 | NKX2-5 NKX2-5 Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2-5 gene.-Interactions:NKX2-5 has been shown to interact with GATA4 and TBX5.... |
Nongoitrous congenital hypothyroidism has been described as the "most prevalent inborn endocrine disorder".
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 endocrinologistPediatric endocrinology
Pediatric endocrinology is a medical subspecialty dealing with variations of physical growth and sexual development in childhood, as well as diabetes and other disorders of the endocrine glands....
is recommended to confirm the diagnosis and initiate treatment. Often a technetium
Technetium
Technetium is the chemical element with atomic number 43 and symbol Tc. It is the lowest atomic number element without any stable isotopes; every form of it is radioactive. Nearly all technetium is produced synthetically and only minute amounts are found in nature...
(Tc-99m pertechnetate) thyroid scan is performed to detect a structurally abnormal gland. A radioactive iodine (RAIU) 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 1–2 weeks of life. Treatment consists of a daily dose of thyroxineThyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
, available as a small tablet. The generic name is levothyroxine
Levothyroxine
Levothyroxine, also L-thyroxine, synthetic T4, or 3,5,3',5'-tetraiodo-L-thyronine, is a synthetic form of thyroxine , used as a hormone replacement for patients with thyroid problems. The natural hormone is chemically in the chiral L-form, as is the pharmaceutical agent...
, 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 μg
Microgram
In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...
/kg daily, typically 37.5 or 44 μg.
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 nursingBreastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
, poor muscle tone, low or hoarse cry, infrequent bowel movements, exaggerated jaundice
Neonatal jaundice
Neonatal jaundice or Neonatal hyperbilirubinemia is a yellowing of the skin and other tissues of a newborn infant. A bilirubin level of more than 85 umol/l manifests clinical jaundice in neonates whereas in adults a level of 34 umol/l would look icteric...
, 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
Umbilical hernia
Congenital umbilical hernia is a congenital malformation, common in infants of African descent. Among adults, it is three times more common in women than in men; among children, the ratio is roughly equal...
, and a large tongue (macroglossia
Macroglossia
Macroglossia is the medical term for unusual enlargement of the tongue. Severe enlargement of the tongue can cause cosmetic and functional difficulties including in speaking, eating, swallowing and sleeping.- Amyloid Disorders :...
).
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 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
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
provide as large a benefit for as small an effort.
See also
- HypothyroidismHypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
- ThyroidThyroidThe thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...