Congenital hypothyroidism
Congenital hypothyroidism is a thyroid hormone deficiency present at birth. If untreated soon after birth, severe congenital hypothyroidism can lead to growth failure and permanent intellectual disability.Untreated congenital hypothyroidism is also referred to as cretinism. Infants born with congenital hypothyroidism may be asymptomatic, or may display mild symptoms that go unrecognized as a problem. Significant deficiency may cause excessive sleeping, reduced interest in nursing, poor muscle tone, low or hoarse cry, infrequent bowel movements, significant jaundice, and low body temperature.
Causes of congenital hypothyroidism include iodine deficiency, developmental defect in the thyroid gland or the hypothalamus/pituitary either due to a genetic defect or an unknown cause, or dysfunction of the thyroid gland or the thyroid hormone. The source of the CH can occur at the level of the hypothalamus/pituitary gland or the thyroid gland. In both cases, the initial newborn screening will reflect low free thyroid hormone levels, with elevated thyroid stimulating hormone in primary CH and low/normal TSH in central CH.
Treatment consists of a daily dose of thyroid hormone by mouth. Because the treatment is simple, effective, and inexpensive, most high-income countries utilize newborn screening with blood thyroid stimulating hormone levels to detect congenital hypothyroidism. Most children with congenital hypothyroidism who are appropriately treated with thyroxine grow and develop normally in all respects. Approximately 1 in 4000 newborns have a severe deficiency of thyroid function; a greater number have a mild or moderate deficiency. Incidence of primary CH is 1 in every 2000 to 3000 births, while the incidence of central CH is much lower occurring in 1 of every 16,000 to 30,000 births.
Signs and 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, significant jaundice, and low body temperature. If the fetal thyroid hormone deficiency is severe because of complete absence of the gland, physical features may include a larger anterior fontanel, persistence of a posterior fontanel, an umbilical hernia, and a large tongue.In the era before newborn screenings, less than half of cases of severe hypothyroidism were recognized in the first month of life. As the months progressed, these babies would grow poorly and have significant neurologic and developmental delays. 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.
Cause
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 or underdeveloped gland. However, recent studies have shown an increase in the number of cases caused by gland in situ. 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. Neonatal hypothyroidism has been reported in cases of infants exposed to lithium, a mood stabilizer used to treat bipolar disorder, in utero. In another systematic review, topical iodine was associated with transient hypo- or hyperthyroidism, particularly in preterm babies born before 32 weeks of gestation.In some instances, hypothyroidism detected by screening may be transient. One common cause of this is the presence of maternal antibodies that temporarily impair thyroid function for several weeks. Preterm or ill neonates may also have a delayed rise in TSH, leading to false-positive newborn screenings and transiently low thyroid hormones. In these cases, a follow-up screening, typically at 4 to 6 weeks, is recommended to re-evaluate the thyroid hormone deficiency.
The word "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 many other 19th century medical terms, acquired pejorative connotations as it became used in lay speech. It is now deprecated; ICD-11 uses "congenital hypothyroidism due to iodine deficiency" with additional specifiers for the various types of endemic cretinism.
Genetics
Congenital hypothyroidism can also occur due to genetic defects of thyroxine or triiodothyronine synthesis within a structurally normal gland. Among specific defects are thyrotropin 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:
| OMIM | Name | Gene |
| congenital hypothyroidism, nongoitrous 1 CHNG1 | TSHR | |
| CHNG2 | PAX8 | |
| CHNG3 | ? at 15q25.3-q26.1 | |
| CHNG4 | TSHB | |
| CHNG5 | NKX2-5 |
Nongoitrous congenital hypothyroidism has been described as the "most prevalent inborn endocrine disorder".