Congenital hypothyroidism

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Congenital hypothyroidism
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6 week old female with jaundice due to hypothyroidism.
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Congenital hypothyroidism (CH) is thyroid hormone deficiency present at birth. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent intellectual disability. Infants born with congenital hypothyroidism may show no effects, or may display mild effects that often 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.[ citation needed ]

Contents

Causes of congenital hypothyroidism include iodine deficiency and a developmental defect in the thyroid gland, either due to a genetic defect or of unknown cause.

Treatment consists of a daily dose of thyroid hormone (thyroxine) by mouth. Because the treatment is simple, effective, and inexpensive, most of the developed world utilizes newborn screening with blood thyroid stimulating hormone (TSH) levels to detect congenital hypothyroidism. Most children with congenital hypothyroidism correctly 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.

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 (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). [1]

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 babies 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. [1]

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 (athyreosis) or underdeveloped (hypoplastic) gland. However, recent studies have shown an increase in the number of cases caused by gland in situ (termed dyshormonogenesis when there is a defect in hormone production). [2] 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. [3] Neonatal hypothyroidism has been reported in cases of infants exposed to lithium, a mood stabilizer used to treat bipolar disorder, in utero . [4]

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. [5]

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 so many other 19th century medical terms, acquired pejorative connotations as it became used in lay speech. It is now deprecated; ICD-10 uses "congenital iodine deficiency syndrome" with additional specifiers for the various types.[ citation needed ]

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 (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. [6] Genetic types of nongoitrous congenital hypothyroidism include:

OMIM NameGene
275200 congenital hypothyroidism, nongoitrous 1 CHNG1 TSHR
218700 CHNG2 PAX8
609893 CHNG3 ? at 15q25.3-q26.1
275100 CHNG4 TSHB
225250 CHNG5 NKX2-5

Nongoitrous congenital hypothyroidism has been described as the "most prevalent inborn endocrine disorder". [7]

Diagnosis

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 (Heel prick). [1]

Evaluation

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 initiate treatment. A technetium (Tc-99m pertechnetate) thyroid scan detects a structurally abnormal gland, while a radioactive iodine (RAIU) exam identifies congenital absence or a defect in organification (a process necessary to make thyroid hormone).[ citation needed ]

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 thyroxine, available as a small tablet. The generic name is levothyroxine, and several brands are available. The tablet is crushed and given to the baby with a small amount of water or milk. The most commonly recommended dose range is 10-15 μg/kg daily, typically 12.5 to 37.5 or 44 μg. [8] 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 grow.[ citation needed ]

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. [9]

Congenital hypothyroidism is the most common preventable cause of intellectual disability. Few treatments in the practice of medicine provide as large a benefit for as small an effort. The developmental quotient (DQ, as per Gesell Developmental Schedules) of children with hypothyroidism at age 24 months that have received treatment within the first 3 weeks of birth is summarised below:[ citation needed ]

.Adaptive behaviorFine motorGross motorLanguagePersonal-social behavior
Severe CH9289908990
Moderate CH9797989696
Mild CH1009910099100

[10]

Epidemiology

Congenital hypothyroidism (CH) occurs in 1:1300 to 1:4000 births worldwide. [2] [11] [12] [13] [14] The differences in CH-incidence are more likely due to iodine deficiency thyroid disorders or to the type of screening method than to ethnic affiliation. [11] CH is caused by an absent or defective thyroid gland classified into agenesis (22-42%), ectopy (35-42%) and gland in place defects (24-36%). [11] [15] It is also found to be of increased association with female sex and gestational age >40 weeks. [15]

Related Research Articles

<span class="mw-page-title-main">Congenital iodine deficiency syndrome</span> Medical condition

Congenital iodine deficiency syndrome is a medical condition present at birth marked by impaired physical and mental development, due to insufficient thyroid hormone (hypothyroidism) often caused by insufficient dietary iodine during pregnancy. It is one cause of underactive thyroid function at birth, called congenital hypothyroidism, historically referred to as cretinism (obsolete). If untreated, it results in impairment of both physical and mental development. Symptoms may include goiter, poor length growth in infants, reduced adult stature, thickened skin, hair loss, enlarged tongue, a protruding abdomen; delayed bone maturation and puberty in children; and mental deterioration, neurological impairment, impeded ovulation, and infertility in adults.

<span class="mw-page-title-main">Hyperthyroidism</span> Thyroid gland disease that involves an overproduction of thyroid hormone.

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. It is noted that thyrotoxicosis is related to hyper-kinetic movement disorders including chorea and myoclonus. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature and often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

<span class="mw-page-title-main">Thyroid</span> Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyroid is located at the front of the neck, below the Adam's apple. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid. The thyroid gland secretes three hormones: the two thyroid hormones – triiodothyronine (T3) and thyroxine (T4) – and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis, and in children, growth and development. Calcitonin plays a role in calcium homeostasis. Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the anterior pituitary gland. TSH is regulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus.

<span class="mw-page-title-main">Graves' disease</span> Autoimmune endocrine disease

Graves' disease, also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyroid. Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy. About 25 to 30% of people with the condition develop eye problems.

<span class="mw-page-title-main">Hypothyroidism</span> Endocrine disease

Hypothyroidism is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goiter. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

<span class="mw-page-title-main">Myxedema</span> Medical condition

Myxedema is a term used synonymously with severe hypothyroidism. However, the term is also used to describe a dermatological change that can occur in hyperthyroidism and (rare) paradoxical cases of hypothyroidism. In this latter sense, myxedema refers to deposition of mucopolysaccharides in the dermis, which results in swelling of the affected area. One manifestation of myxedema occurring in the lower limb is pretibial myxedema, a hallmark of Graves disease, an autoimmune form of hyperthyroidism. Myxedema can also occur in Hashimoto thyroiditis and other long-standing forms of hypothyroidism.

<span class="mw-page-title-main">Hashimoto's thyroiditis</span> Autoimmune disease

Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarge, forming a painless goiter. Some people eventually develop hypothyroidism with accompanying weight gain, fatigue, constipation, depression, hair loss, and general pains. After many years the thyroid typically shrinks in size. Potential complications include thyroid lymphoma. Furthermore, because it is common for untreated patients of Hashimoto's to develop hypothyroidism, further complications can include, but are not limited to, high cholesterol, heart disease, heart failure, high blood pressure, myxedema, and potential pregnancy problems.

<span class="mw-page-title-main">Levothyroxine</span> Thyroid hormone

Levothyroxine, also known as L-thyroxine, is a manufactured form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency (hypothyroidism), including Hashimoto's disease and a severe form known as myxedema coma. It may also be used to treat and prevent certain types of thyroid tumors. It is not indicated for weight loss. Levothyroxine is taken by mouth or given by intravenous injection. Maximum effect from a specific dose can take up to six weeks to occur.

Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine deficiency syndrome due to untreated congenital hypothyroidism, which results in developmental delays and other health problems. Iodine deficiency is an important global health issue, especially for fertile and pregnant women. It is also a preventable cause of intellectual disability.

<span class="mw-page-title-main">Complications of pregnancy</span> Medical condition

Complications of pregnancy are health problems that are related to pregnancy. Complications that occur primarily during childbirth are termed obstetric labor complications, and problems that occur primarily after childbirth are termed puerperal disorders. Severe complications of pregnancy, childbirth, and the puerperium are present in 1.6% of mothers in the US, and in 1.5% of mothers in Canada. In the immediate postpartum period (puerperium), 87% to 94% of women report at least one health problem. Long-term health problems are reported by 31% of women.

<span class="mw-page-title-main">Thyroid disease</span> Medical condition

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

<span class="mw-page-title-main">Liothyronine</span>

Liothyronine is a manufactured form of the thyroid hormone triiodothyronine (T3). It is most commonly used to treat hypothyroidism and myxedema coma. It can be taken by mouth or by injection into a vein.

Desiccated thyroid, also known as thyroid extract, is thyroid gland that has been dried and powdered for medical use. It is used to treat hypothyroidism. It is less preferred than levothyroxine. It is taken by mouth. Maximal effects may take up to 3 weeks to occur.

<span class="mw-page-title-main">Sodium/iodide cotransporter</span> Mammalian protein found in Homo sapiens

The sodium/iodide cotransporter, also known as the sodium/iodide symporter (NIS), is a protein that in humans is encoded by the SLC5A5 gene. It is a transmembrane glycoprotein with a molecular weight of 87 kDa and 13 transmembrane domains, which transports two sodium cations (Na+) for each iodide anion (I−) into the cell. NIS mediated uptake of iodide into follicular cells of the thyroid gland is the first step in the synthesis of thyroid hormone.

Thyrotoxic myopathy (TM) is a neuromuscular disorder that develops due to the overproduction of the thyroid hormone thyroxine. Also known as hyperthyroid myopathy, TM is one of many myopathies that lead to muscle weakness and muscle tissue breakdown. Evidence indicates the onset may be caused by hyperthyroidism. There are two known causes of hyperthyroidism that lead to development thyrotoxic myopathy including a multinodular goiter and Graves' disease. Physical symptoms of TM may include muscle weakness, the breakdown of muscle tissue, fatigue, and heat intolerance. Physical acts such as lifting objects and climbing stairs may become increasingly difficult. If untreated, TM can be an extremely debilitating disorder that can, in extreme rare cases, lead to death. If diagnosed and treated properly the effects can be controlled and in most cases reversed leaving no lasting effects.

<span class="mw-page-title-main">IGSF1</span> Protein-coding gene in the species Homo sapiens

Immunoglobulin superfamily, member 1 is a plasma membrane glycoprotein encoded by the IGSF1 gene, which maps to the X chromosome in humans and other mammalian species.

<span class="mw-page-title-main">Thyroid hormones</span> Hormones produced by the thyroid gland

Thyroid hormones are any hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre.

Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnancy, or after childbirth. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy. The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%. If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease. Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards. This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.

Thyroid disease in women is an autoimmune disease that affects the thyroid in women. This condition can have a profound effect during pregnancy and on the child. It also is called Hashimoto's thyroiditis (theye-royd-EYET-uhss). During pregnancy, the infant may be seriously affected and have a variety of birth defects. Many women with Hashimoto's disease develop an underactive thyroid. They may have mild or no symptoms at first, but symptoms tend to worsen over time. If a woman is pregnant and has symptoms of Hashimoto's disease, the clinician will do an exam and order one or more tests.

References

  1. 1 2 3 "Hypothyroidism". The Lecturio Medical Concept Library. Retrieved 27 July 2021.
  2. 1 2 Worth, Chris; Hird, Beverly; Tetlow, Lesley; Wright, Neville; Patel, Leena; Banerjee, Indraneel (14 November 2019). "Thyroid scintigraphy differentiates subtypes of congenital hypothyroidism". Archives of Disease in Childhood. 106 (1): archdischild-2019-317665. doi:10.1136/archdischild-2019-317665. PMID   31727620. S2CID   208039220.
  3. ↑ Nagayama J, Kohno H, Kunisue T, et al. (2007). "Concentrations of organochlorine pollutants in mothers who gave birth to neonates with congenital hypothyroidism". Chemosphere . 68 (5): 972–6. Bibcode:2007Chmsp..68..972N. doi:10.1016/j.chemosphere.2007.01.010. PMID   17307219.
  4. ↑ Frassetto, F; Tourneur Martel, F; Barjhoux, CE; Villier, C; Bot, BL; Vincent, F (November 2002). "Goiter in a newborn exposed to lithium in utero". The Annals of Pharmacotherapy. 36 (11): 1745–8. doi:10.1345/aph.1C123. PMID   12398572. S2CID   24175902.
  5. ↑ "Congenital hypothyroidism". Orphanet. August 2010. Retrieved 22 May 2012.
  6. ↑ "Hypopituitarism". The Lecturio Medical Concept Library. Retrieved 27 July 2021.
  7. ↑ Grasberger H, Vaxillaire M, Pannain S, et al. (December 2005). "Identification of a locus for nongoitrous congenital hypothyroidism on chromosome 15q25.3-26.1". Hum. Genet. 118 (3–4): 348–55. doi:10.1007/s00439-005-0036-6. PMID   16189712. S2CID   19782628.
  8. ↑ LaFranchi SH, Austin J (2007). "How should we be treating children with congenital hypothyroidism?". J. Pediatr. Endocrinol. Metab. 20 (5): 559–78. doi:10.1515/JPEM.2007.20.5.559. PMID   17642417. S2CID   638254.
  9. ↑ Moltz KC, Postellon DC (1994). "Congenital hypothyroidism and mental development". Compr Ther . 20 (6): 342–6. PMID   8062543.
  10. ↑ Huo K, Zhang Z, Zhao D, Li H, Wang J, Wang X, Feng H, Wang X, Zhu C (2011). "Risk factors for neurodevelopmental deficits in congenital hypothyroidism after early substitution treatment". Endocrine Journal . 58 (5): 355–61. doi: 10.1507/endocrj.k10e-384 . PMID   21467693.
  11. 1 2 3 Klett, M (1997). "Epidemiology of congenital hypothyroidism". Experimental and Clinical Endocrinology & Diabetes. 105 Suppl 4: 19–23. doi:10.1055/s-0029-1211926. PMID   9439909.
  12. ↑ Harris, KB; Pass, KA (July 2007). "Increase in congenital hypothyroidism in New York State and in the United States". Molecular Genetics and Metabolism. 91 (3): 268–77. doi:10.1016/j.ymgme.2007.03.012. PMID   17512233.
  13. ↑ Deladoey, J.; Belanger, N.; Van Vliet, G. (1 August 2007). "Random Variability in Congenital Hypothyroidism from Thyroid Dysgenesis over 16 Years in Quebec". Journal of Clinical Endocrinology & Metabolism. 92 (8): 3158–3161. doi: 10.1210/jc.2007-0527 . PMID   17504897.[ permanent dead link ]
  14. ↑ Olney, RS; Grosse, SD; Vogt RF, Jr (May 2010). "Prevalence of congenital hypothyroidism--current trends and future directions: workshop summary". Pediatrics. 125 Suppl 2: S31-6. doi: 10.1542/peds.2009-1975C . PMID   20435715.
  15. 1 2 Medda, E; Olivieri, A; Stazi, MA; Grandolfo, ME; Fazzini, C; Baserga, M; Burroni, M; Cacciari, E; Calaciura, F; Cassio, A; Chiovato, L; Costa, P; Leonardi, D; Martucci, M; Moschini, L; Pagliardini, S; Parlato, G; Pignero, A; Pinchera, A; Sala, D; Sava, L; Stoppioni, V; Tancredi, F; Valentini, F; Vigneri, R; Sorcini, M (December 2005). "Risk factors for congenital hypothyroidism: results of a population case-control study (1997–2003)". European Journal of Endocrinology. 153 (6): 765–73. doi: 10.1530/eje.1.02048 . PMID   16322381.
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