Prinsip Diagnosis Dan Terapi Skenario: Learning Objectives

LEARNING OBJECTIVES
1. PRINSIP DIAGNOSIS DAN TERAPI SKENARIO
Clinical description
The clinical features of congenital hypothyroidism are often subtle and many newborn infants remain undiagnosed at
birth [8,9]. This is due in part to passage of maternal thyroid hormone across the placenta. This is measured in
umbilical cord serum to be 25-50 percent of normal [10]. This provides a protective effect, especially to the fetal brain
[11]. Also, the most common form of congenital hypothyroidism has some moderately functioning thyroid tissue [12].
The slow development of obvious clinical symptoms [13], coupled with the importance of early treatment led to the
implementation of widespread newborn screening for this condition [2]. However, newborn screening for
hypothyroidism is not done in many third world countries. Only an estimated 1/3 of the worldwide birth population is
screened. It is therefore important that clinicians are able to recognize and treat the disorder.
Symptoms
Symptoms of congenital hypothyroidism are initially nondescript;
however, the maternal and pregnancy history may provide some
clues. In twenty percent, gestation extends beyond forty-two weeks
[8]. One may also find evidence of maternal autoimmune thyroid
disease or an iodine deficient diet. Inadvertent radioactive Iodine
treatment during pregnancy is rare. Once home, these babies are
quiet and may sleep through the night. Additional symptoms include
a hoarse cry and constipation.Neonatal hyperbilirubinemia for more
than three weeks is common. This is due to immaturity of hepatic
glucuronyl transferase [8,14]. Table 2 illustrates some symptoms
that were present at the time of diagnosis by newborn screening. In
this study, the most common symptoms were prolonged jaundice,
lethargy, feeding difficulty and constipation [14].
Signs
Up to one third have a birth
weight greater than the ninetieth
percentile [8]. On initial examination, the
most common signs are umbilical hernia,
macroglossia and cold or mottled skin
[14]. Thyroid hormone is also important
in the formation and maturation of bone
[15,16].This can lead to a wide posterior
fontanel of greater than 5 mm. This,
along with persistent jaundice and poor
feeding are the most striking clinical
features [12]. A few infants with
congenital hypothyroidism may
haveapalpablegoiter.Thisis usually found
in thyroid dyshormonogenesis where
there is a defect in thyroid hormone
production. Pendred syndrome
mentioned below can present with
deafness and a palpable goiter. Other forms of dyshormogenesis are due to defects in enzyme function within the
thyroid gland and are discussed further in the section on etiology.
The typical appearance of a hypothyroid infant before the advent of newborn screening is shown in the infant
in Figure 1. Features include jaundice, a puffy face and a wide posterior fontanelle with open sutures. The nasal bridge
is flat and the eyes exhibit pseudohypertelorism. The mouth may be slightly open revealing macroglossia. Further
examination would reveal bradycardia and a protuberant abdomen with a large umbilical hernia. Neurologic
examination findings include hypotonia with delayed reflexes. Skin may be cool to touch and mottled in appearance
reflecting circulatory compromise [8]. X-rays can reveal absent femoral epiphyses in up to 54% [4]
Etiology
Permanent congenital hypothyroidism may be due to primary or secondary (central) causes. Primary causes
include defects of thyroid gland development, deficiencies in thyroid hormone production, and hypothyroidism
resulting from defects of TSH binding or signal transduction. Peripheral hypothyroidism results from defects in thyroid
hormone transport, metabolism, or resistance to thyroid hormone action. Secondary or central causes include defects
of thyrotropin releasing hormone (TRH) formation or binding and TSH production. These are covered briefly in this
review and are listed in Table 3.
Transient hypothyroidism may be caused by maternal or neonatal factors. Maternal factors include
antithyroid medications, transplacental thyrotropin receptor blocking antibodies and exposure to iodine deficiency or
excess. Neonatal factors include, neonatal iodine deficiency or excess, congenital liver hemangiomas and mutations
in the genes encoding for DUOX and DUOXA2
Permanent congenital hypothyroidism

In iodine sufficient countries, 85% of congenital hypothyroidism is due to thyroid dysgenesis. This term refers to an
aberration of the embryological development of the thyroid gland. The remaining 10-15% of cases can be attributed
to the inborn errors of thyroid hormone synthesis, also called dyshormonogenesis, or to defects in peripheral thyroid
hormone transport, metabolism, or action [27].
Transient congenital hypothyroidism

Transient congenital hypothyroidism is found to be more common in Europe (1:100) than the United States
(1:50,000) [3]. In a report of over twenty years in the French newborn screening program, the incidence of
transient congenital hypothyroidism was found to be 40 percent [3]. Causes of transient congenital hypothyroidism
include:
• Iodine deficiency - Iodine deficiency is more common in European countries, especially in preterm infants; this is
due mainly to maternal iodine deficient diets [3,12,56].
• Transfer of maternal blocking antibodies – Maternal antithyroid antibodies can cross the placenta and block the TSH
receptor in the neonatal thyroid. This effect can last up to 3 to 6 months after birth as maternal antibody levels fall
[57,58].
• Fetal exposure to antithyroid drugs – Maternal antithyroid drugs can cause decreased neonatal thyroid hormone
synthesis which lasts for a few days to two weeks after birth.
• Maternal iodine exposure - Maternally administered amiodarone may cause transient hypothyroidism in their infants.
This seems to resolve at around 4-5 months of age and can be associated with adverse neurologic outcomes [59].
Transient hypothyroidism also occurs when iodine antiseptic compounds are used on mothers or after exposure to
iodinated contrast agents; however, this may be related to the type and duration of exposure as a recent study showed
no abnormal thyroid functions in the infants of 21 mothers given iodide contrast during pregnancy [60].
• Neonatal Iodine exposure - Exposure of newborns to high amounts of iodine can cause hypothyroidism. This can
occur especially in preterm infants[61].
• Liver hemangiomas - There are reports of congenital liver hemangiomas that produce large amounts of the enzyme
type 3 iodothyronine deiodinase. This produces a consumptive type of hypothyroidism in which large doses of
thyroxine are required to maintain euthyroidism. Serum T4 levels are low, TSH is elevated, and reverse T3 levels are
also increased. Hypothyrodism resolves as the tumor involutes or is treated [62].
• Mutations in DUOX2 (THOX2)andDUOXA2 can lead to transient congenital hypothyroidism as previously
described [48,49].
Diagnostic studies to determine an underlying etiology
2. INTERPRETASI PEMERIKSAAN LABORATORIUM, SCREENING DAN FOTO XRAY
LENG
3. PATOGENESIS KASUS SKENARIO
Permanent congenital hypothyroidism
In iodine sufficient countries, 85% of congenital hypothyroidism is due to thyroid dysgenesis. This term refers to an
aberration of the embryological development of the thyroid gland. The remaining 10-15% of cases can be attributed
to the inborn errors of thyroid hormone synthesis, also called dyshormonogenesis, or to defects in peripheral thyroid
hormone transport, metabolism, or action [27].
Transient congenital hypothyroidism

Transient congenital hypothyroidism is found to be more common in Europe (1:100) than the United States
(1:50,000) [3]. In a report of over twenty years in the French newborn screening program, the incidence of
transient congenital hypothyroidism was found to be 40 percent [3]. Causes of transient congenital hypothyroidism
include:
• Iodine deficiency - Iodine deficiency is more common in European countries, especially in preterm infants; this is
due mainly to maternal iodine deficient diets [3,12,56].
• Transfer of maternal blocking antibodies – Maternal antithyroid antibodies can cross the placenta and block the TSH
receptor in the neonatal thyroid. This effect can last up to 3 to 6 months after birth as maternal antibody levels fall
[57,58].
• Fetal exposure to antithyroid drugs – Maternal antithyroid drugs can cause decreased neonatal thyroid hormone
synthesis which lasts for a few days to two weeks after birth.
• Maternal iodine exposure - Maternally administered amiodarone may cause transient hypothyroidism in their infants.
This seems to resolve at around 4-5 months of age and can be associated with adverse neurologic outcomes [59].
Transient hypothyroidism also occurs when iodine antiseptic compounds are used on mothers or after exposure to
iodinated contrast agents; however, this may be related to the type and duration of exposure as a recent study showed
no abnormal thyroid functions in the infants of 21 mothers given iodide contrast during pregnancy [60].
• Neonatal Iodine exposure - Exposure of newborns to high amounts of iodine can cause hypothyroidism. This can
occur especially in preterm infants[61].
• Liver hemangiomas - There are reports of congenital liver hemangiomas that produce large amounts of the enzyme
type 3 iodothyronine deiodinase. This produces a consumptive type of hypothyroidism in which large doses of
thyroxine are required to maintain euthyroidism. Serum T4 levels are low, TSH is elevated, and reverse T3 levels are
also increased. Hypothyrodism resolves as the tumor involutes or is treated [62].
• Mutations in DUOX2 (THOX2)andDUOXA2 can lead to transient congenital hypothyroidism as previously
described [48,49].
SUMBER :
Rastogi M.V & LaFranchi S.H. 2012. CONGENITAL HYPOTHYROIDISM. Orphanet Journal of Rare Diseases.
Vol 5 no 17. Viewed 29 Maret 2017. From <
https://www.google.co.id/url?sa=t&rct=j&q=&esrc=s&source=web&cd=3&cad=rja&uact
=8&ved=0ahUKEwjr1cWf-
fzSAhXHfLwKHQbyACMQFgg2MAI&url=http%3A%2F%2Fciteseerx.ist.psu.edu%2Fviewd
oc%2Fdownload%3Fdoi%3D10.1.1.354.4159%26rep%3Drep1%26type%3Dpdf&usg=AFQ
jCNFqXb60e4EMec-MHEQN-SL2qv3SAQ&sig2=lpU4nORfAglJKYoaSTqTow >

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LEARNING OBJECTIVES

1. PRINSIP DIAGNOSIS DAN TERAPI SKENARIO

Permanent congenital hypothyroidism

Transient congenital hypothyroidism

Transient congenital hypothyroidism

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