congenital hypothyroidism

先天性甲状腺機能低下症

WordNet

1. present at birth but not necessarily hereditary; acquired during fetal development (同)inborn, innate
2. an underactive thyroid gland; a glandular disorder resulting from insufficient production of thyroid hormones

PrepTutorEJDIC

1. (病気・身体的欠陥など)生まれつきの,先天的な
2. 甲状腺機能不全

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/20 10:26:29」(JST)

wiki en

[Wiki en表示]

Congenital hypothyroidism
6 week old female with symptoms of jaundice due to hypothyrodism. This patient was treated with supplemental thyroid hormonal therapy, and appeared to be a normal healthy child at 1 year of age.
Classification and external resources
ICD-10	E00, E03.0, E03.1
ICD-9	243
DiseasesDB	6612
MedlinePlus	001193
MeSH	D003409

Congenital hypothyroidism (Styria), copper engraving, 1815

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 intellectual disability. 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.

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, 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.

• 3 month old infant with untreated CH; picture demonstrates hypotonic posture, myxedematous facies, macroglossia, and umbilical hernia

• Close up of face, showing myxedematous facies, macroglossia, and skin mottling

• Close up showing abdominal distension and umbilical hernia.

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. 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. One common cause of this is the presence of maternal antibodies that 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.

Genetic types of nongoitrous congenital hypothyroidism include:

OMIM	Name	Gene
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".

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).

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. 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).

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. 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.

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 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 is summarised below:

.	Adaptive behavior	Fine motor	Gross motor	Language	Personal-social behavior
Severe CH	92	89	90	89	90
Moderate CH	97	97	98	96	96
Mild CH	100	99	100	99	100

Epidemiology

Neonatal thyroid screening programs from all over the world have revealed that congenital hypothyroidism (CH) occurs with an incidence of 1:3000 to 1:4000. 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. 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%). It is also found to be of increased association with female gender and gestational age >40 weeks.

References

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 先天性甲状腺機能低下症の臨床的特徴および検出 clinical features and detection of congenital hypothyroidism
• 2. 先天性甲状腺機能低下症の治療および予後 treatment and prognosis of congenital hypothyroidism
• 3. 妊娠中の甲状腺疾患の概要 overview of thyroid disease in pregnancy
• 4. 小児および思春期における後天性甲状腺機能低下症 acquired hypothyroidism in childhood and adolescence
• 5. 妊娠中の甲状腺機能低下症：臨床症状、診断、および治療 hypothyroidism during pregnancy clinical manifestations diagnosis and treatment

English Journal

• Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: identification a cryptic donor splice site in the exon 19.

• Targovnik HM, Edouard T, Varela V, Tauber M, Citterio CE, González-Sarmiento R, Rivolta CM.SourceLaboratorio de Biología Molecular, Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, 1113 Buenos Aires, Argentina. htargovn@ffyb.uba.ar
• Molecular and cellular endocrinology.Mol Cell Endocrinol.2012 Jan 2;348(1):313-21. Epub 2011 Sep 21.
• Thyroglobulin (TG) is a homodimeric glycoprotein synthesized by the thyroid gland. To date, 52 mutations of the TG gene have been identified in humans. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report a French patient with congenital hypothyro
• PMID 21958696

• Molecular analysis of the PAX8 gene in a sample of Mexican patients with primary congenital hypothyroidism: identification of the recurrent p.Arg31His mutation.

• Alcántara-Ortigoza MA, González-Del Angel A, Martínez-Cruz V, Vela-Amieva M, Sánchez-Pérez C, Moreno-Rojas R, Estandía-Ortega B, Hernández-Martínez N.SourceLaboratorio de Biología Molecular, Departamento de Genética Humana, Instituto Nacional de Pediatría, México, Distrito Federal, México Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, México, Distrito Federal, México Laboratorio de Seguimiento del Neurodesarrollo, Instituto Nacional de Pediatría, México, Distrito Federal, México E-mail: malcantaraortigoza@gmail.com.
• Clinical endocrinology.Clin Endocrinol (Oxf).2012 Jan;76(1):148-50. doi: 10.1111/j.1365-2265.2011.04153.x.
• PMID 21689132

Japanese Journal

• 先天性甲状腺疾患と遺伝子異常 (内分泌) -- (臨床分野での進歩)

• 中島 康代,山田 正信
• Annual review. 糖尿病・代謝・内分泌, 198-203, 2014
• NAID 40019974946

• Overall usefulness of newborn screening for congenital hypothyroidism by using free thyroxine measurement

• Soneda Akiko,Adachi Masanori,Muroya Koji,Asakura Yumi,Yamagami Yuji,Hirahara Fumiki
• Endocrine Journal, 2014
• … In Kanagawa Prefecture, Japan, simultaneous measurements of free T4 (FT4) and TSH levels are performed during newborn screening for congenital hypothyroidism (CH). …
• NAID 130004677942

• IDENTIFICATION OF NOVEL GENETIC MUTATIONS IN JAPANESE PATIENTS WITH SEVERE CONGENITAL HYPOTHYROIDISM

• Adachi Hiroyuki,Takahashi Ikuko,Arai Hirokazu [他],Takahashi Tsutomu
• 秋田医学 40(2), 71-78, 2013-11-21
• … Objective : The prevalence of genetic mutations in congenital hypothyroidism (CH) remains undetermined. …
• NAID 110009658219

Related Links

• Congenital hypothyroidism - Genetics Home Reference

Most cases of congenital hypothyroidism are sporadic, which means they occur in people with no history of the disorder in their family. When inherited, the condition usually has an autosomal recessive inheritance ...

• Congenital Hypothyroidism: Practice Essentials, Background ...

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.

Related Pictures

---

★リンクテーブル★

リンク元	「クレチン症」
関連記事	「congenita」「congenital」「hypothyroidism」

「クレチン症」

　　[★]

英

cretinism

同

新生児甲状腺機能低下症 hypothyroidism of the newborn neonatal hyperthyroidism, hypothyroidism of the newborn

先天性甲状腺機能低下症 congenital hypothyroidism

クレチン病

関

甲状腺機能低下症、新生児マススクリーニング。成長#ホルモン(乳児期の成長にはインスリンと甲状腺ホルモンが必要)

概念

• 新生児マススクリーニングで見いだされる最も頻度の高い疾患であり、知能障害、発育障害、クレチン顔貌(鞍鼻など)、徐脈が特徴的である。

疫学

• 1/4,800 ないし 1/2,200

病因

• TRHとTSHの異常

• TSH欠損
• TRH受容体異常

• ヨード転送障害

• NISの異常による

• ヨード有機化障害
• サイログロブリン合成異常

• Tg合成異常：8-10万人に1人

• 遺伝子表現の調節異常

• 甲状腺特異的な転写因子、tyroid transcription factor 1(TTF1), TTF2, PAX8

YN.D-37

症候

• 精神発達遅滞、発育遅延、食欲不良、巨舌、呼吸困難(巨舌による)、生理的黄疸の遷延、臍ヘルニア
• 便秘、低体温 (104I039)

身体所見

• (骨成熟遅延による)大泉門、小泉門開大

検査

• 新生児マススクリーニング：RIA法により血中のTSH上昇、T4低下でスクリーニングを行う

治療

• 甲状腺ホルモン補充療法

参考

uptodate

• 1. [charged] 先天性甲状腺機能低下症の臨床的特徴および検出 - uptodate [1]
• 2. [charged] 先天性甲状腺機能低下症の治療および予後 - uptodate [2]

国試

• 104I039

「congenita」

　　[★]

• adj.

• (後置するラテン語形容詞)先天性の

関

congenital、congenitally

• ex.

• dyskeratosis congenita、myotonia congenita

「congenital」

　　[★]

• adj.

• 生まれつきの、先天的な

　 　

「hypothyroidism」

　　[★] 甲状腺機能低下症