Congenital Hypothyroidism
Abdullah M. Al-Olayan.
MBBS, SBP, ABP.
Assistant Professor of Pediatrics.
Pediatric Pulmonolgist.
Objectives :
1-Introduction.
2-Epidemiology.
3-Etiology.
3-Clinical Manifestations.
4-Diagnosis.
5-Management.
Introduction :
Congenital hypothyroidism :
Is one of the most common preventable
causes of intellectual disability
(mental retardation).
Introduction :
There is an inverse relationship between
age at clinical diagnosis and treatment
initiation and (IQ) later in life,
so that the longer the condition goes
undetected, the lower the IQ.
Introduction :
Most newborn babies with congenital
hypothyroidism have few or no clinical
manifestations of thyroid hormone
deficiency.
For these reasons, newborn screening
programs were developed in the
mid-1970s to detect this condition as early
as possible.
Epidemiology :
Epidemiology :
Epidemiology :
Epidemiology :
Nearly all screening programs report
2:1 female to male ratio.
Mostly with thyroid ectopy, and less so with
agenesis
Epidemiology :
Thyroid dysgenesis was more prevalent in
white than in black infants,
Where as dyshormonogenesis occurred
equally in these racial groups.
Etiology :
In General :
85 % of congenital hypothyroidism are
sporadic (most caused by thyroid
dysgenesis).
15 % are hereditary (most caused by one of
the inborn errors of thyroid hormone
synthesis)
Etiology :
1-Thyroid Dysgenesis :
The most common cause of congenital
hypothyroidism is some form of thyroid
dysgenesis, (eg, agenesis, hypoplasia, or
ectopy).
Thyroid ectopy accounts for two-thirds of
the cases worldwide
Etiology :
1-Thyroid Dysgenesis :
Although most cases of thyroid dysgenesis
are sporadic, there is evidence of a
familial/genetic component in some
patients.
Etiology :
2-Resistance to TSH :
Mutations in the TSH receptor will present
as primary hypothyroidism, with an
elevated serum TSH and low T4 level.
Etiology :
Etiology :
3-Disorders of thyroid hormone synthesis
and secretion :
Characterized by autosomal recessive
inheritance.
The most common is a defect in thyroid
peroxidase activity that results in impaired
iodide oxidation and organification, and may
be associated with sensory-neural hearing
loss (Pendred syndrome).
Etiology :
3-Disorders of thyroid hormone
synthesis and secretion :
-Defects in iodide transport, caused by a
mutation in the sodium/iodide symporter
gene.
-Defects in the generation of hydrogen
peroxide, a substrate for thyroid peroxidase
in the oxidation of iodide, caused by
mutations in the dual oxidase 2 gene
(DUOX2).
Etiology :
3-Disorders of thyroid hormone
synthesis and secretion :
-Production of abnormal thyroglobulin
molecules, caused by mutations in the
thyroglobulin gene.
-Iodotyrosine deiodinase deficiency, due to
homozygous mutations of the DEHAL1
gene.
Etiology :
4-Defects in thyroid hormone transport :
Passage of thyroid hormone into the cell is
facilitated by plasma membrane
transporters.
A mutation in one such transporter gene,
monocarboxylate transporter 8 (MCT8),
located on the X chromosome.
Etiology :
5-Defects in thyroid hormone
metabolism :
Inherited defects in thyroid hormone
metabolism involve the gene for
selenocysteine insertion sequence-binding
protein 2 (SECISBP-2).
Etiology :
6-Resistance to thyroid hormone :
Mutations in thyroid hormone receptors
(primarily the TH receptor beta gene).
The incidence is approximately 1:40,000
High T4, and T3 levels with normal or slightly
elevated serum TSH levels.
Patients generally do not have clinical
manifestations of hyperthyroidism, and, for
most, no treatment is indicated.
Etiology :
7-Central hypothyroidism :
Hypothalamic or pituitary hypothyroidism.
Screening programs based only on TSH screening
alone will not identify these infants.
Occurs in 1:25,000 to 1:100,000 newborns.
It may be associated with other congenital
syndromes, particularly mid-line defects such as
septo-optic dysplasia or mid-line cleft lip and palate
defects, and may follow birth trauma or asphyxia.
Etiology :
7-Central hypothyroidism :
Most infants with central hypothyroidism ,
have other pituitary hormone deficiencies.
Can be caused by insufficient treatment of
maternal hyperthyroidism during pregnancy.
May persist beyond 6 months of age especially
when maternal thyrotoxicosis occurred before
32 weeks gestation.
Etiology :
8-Transient congenital hypothyroidism :
The causes of transient hypothyroidism in newborn
infants are :
Iodine deficiency. 
Transfer of blocking antibodies or antithyroid 
drugs.
Antithyroid drugs. 
Iodine exposure. 
Large hepatic hemangiomas. 
Mutations in the dual oxidase (DUOX1 and 
DUOX2) gene.
Clinical Manifestations :
The majority (more than 95 percent)
of infants with congenital hypothyroidism
have NO clinical manifestations of
hypothyroidism at birth.
Birth length and weight typically are within
the normal range although birth weight
can be increased and head circumference
also may be increased.
Clinical Manifestations :
Lethargy. 
Slow movement. 
Hoarse cry. 
Feeding problems. 
Constipation. 
Macroglossia. 
Umbilical hernia. 
Large fontanels. 
Hypotonia. 
Dry skin. 
Hypothermia. 
Prolonged jaundice. 
Clinical Manifestations :
Congenital malformations :
CH appears to be associated with an
increased risk of additional congenital
malformations affecting the heart, kidneys,
urinary tract, gastrointestinal and skeletal
systems.
Clinical Manifestations :
Diagnosis :
Infants with abnormal screening results are
recalled for further testing.
At recall, the infant should be examined and
a blood sample is obtained by venipuncture
to confirm the diagnosis of hypothyroidism
Diagnosis :
The findings of low serum T4 or free T4 and high
serum TSH values confirm the diagnosis of primary
hypothyroidism.
Between one and four days of life,
Normal total T4 is about 10 to 22 mcg/dL.
Normal free T4 is about 2 to 5 ng/dL.
Between one and four weeks of life,
Normal total T4 is 7 to 16 mcg/dL
Normal free T4 is 0.8 to 2.0 ng/dL.
Diagnosis :
A normal serum total or free T4 concentration and
a high serum TSH concentration define subclinical
hypothyroidism.
A low serum total and free T4 concentrations in
the presence of low or normal serum TSH
concentrations indicate the presence of central
hypothyroidism.
The combination of a low total T4 and normal free
T4 and TSH indicates the presence of thyroxinebinding globulin (TBG) deficiency.
Diagnosis :
1-Thyroid radionuclide uptake and
imaging :
Provide information about the size and
location of the thyroid gland.
Diagnosis :
1-Thyroid radionuclide uptake and
imaging :
Infants with minor abnormalities in 
thyroid function.
Infants with a small goiter. 
Infants suspected of having transient 
hypothyroidism.
Diagnosis :
2-Thyroid ultrasonography and color
flow Doppler :
Thyroid tissue can be identified by
ultrasonography in infants, but it is not as
reliable as radionuclide imaging in
identifying cases of thyroid dysgenesis.
Diagnosis :
3-Serum thyroglobulin concentration:
Measurement of serum thyroglobulin has been
advocated as a means to distinguish among the
causes of congenital hypothyroidism.
Normal range was 20 to 80 ng/mL
Thyroid agenesis ( 2 to 54 ng/Ml ).
Ectopic thyroid tissue ( 11 to 231 ng/mL).
Goiters (3 to 425 ng/mL).
Diagnosis :
4-Urinary iodine concentration :
Iodine exposure. 
If the infant is born in an area of endemic
goiter.

Management :
The overall goals of treatment are to assure
normal growth and development and
psychometric outcome.
Oral levothyroxine (L-T4) is the treatment
of choice.
Management :
Treatment should be initiated in an infant
with a clearly positive screening test as
soon as confirmatory blood samples have
been drawn, pending results.
Both the timing and dose of thyroid
hormone replacement are important.
Management :
The American Academy of Pediatrics (AAP)
recommends a starting L-T4 dose of
10 to 15 mcg/kg/day.
To restore the serum T4 to >10 mcg/dL or
a free T4 in the upper half of the normal
range for age as rapidly as possible.
Management :
In a literature review identifying 11 studies
evaluating the age of onset of thyroid
hormone treatment, infants started "early"
(12 to 30 days of age) had a mean IQ 15.7
points higher than infants started "later"
(>30 days of age).
Management :
The tablets should not be mixed with soy
formulas or any preparation containing
concentrated iron or calcium, both of
which reduce the absorption of L-T4.
The absorption of L-T4 is somewhat
reduced by administration with food and
formula.
Management :
Treatment goals :
The aim of treatment is to keep the T4 or
fT4 in the upper half of the normal range.
In the first year of life, the serum T4 values
should be 10 to 16 mcg/Dl.
Management :
Recommended follow-up :
Clinical evaluation should be performed
every few months during the first three
years of life.
Management :
The American Academy of Pediatrics recommends
measurement of TFT according to the following schedule :
At 2 and 4 weeks after the initiation of L-T4 treatment.
Every 1 to 2 months during the first 6 months of life 
Every 3 to 4 months between 6 months and 3 years. 
Every 6 to 12 months thereafter until growth is 
complete
Two weeks after any change in dose 
At more frequent intervals when compliance is 
questioned or abnormal results are obtained
Prognosis :
The psychometric outcome is much
improved over the prescreening era, but
some severely affected infants or those
who are inadequately treated in the first
two or three years of life have IQs below
those of normal children.
Summary :
Congenital hypothyroidism is one of the
most common preventable causes of
mental retardation.
Newborn screening programs allow for
early identification and treatment of
affected infants to minimize
complications.
Summary :
85 % of congenital hypothyroidism are
sporadic (most caused by thyroid
dysgenesis).
15 % are hereditary (most caused by one of
the inborn errors of thyroid hormone
synthesis)
Summary :
Infants with abnormal screening results are
recalled for further testing.
If the diagnosis of hypothyroidism is
confirmed,
thyroid radionuclide uptake and imaging,
ultrasonography, serum thyroglobulin assay,
urinary iodine excretion, may be performed
to identify the cause.
Summary :
Oral levothyroxine (L-T4) is the treatment
of choice 10 to 15 mcg/kg/day.
References :
References :
Thank You