2. Congenital Hypothyroidism
• Hypothyroidism results from deficient production of
thyroid hormone, either from a defect in the gland
itself (primary hypothyroidism) or a result of reduced
thyroid-stimulating hormone (TSH) stimulation
(central or hypopituitary hypothyroidism )
• The disorder may be manifested from birth
(congenital) or acquired.
3. Congenital Hypothyroidism
CONGENITAL HYPOTHYROIDISM
Most cases of congenital hypothyroidism are not hereditary
and result from thyroid dysgenesis.
Most infants with congenital hypothyroidism are detected by
newborn screening programs in the 1st few wk after birth,
before obvious clinical symptoms and signs develop.
Although breast milk contains significant amounts of thyroid
hormones, particularly T3, it is inadequate to protect the
breastfed infant who has congenital hypothyroidism, and it
has no effect on neonatal thyroid screening tests.
4. Epidemiology
The prevalence was 1 in 4,000 infants worldwide.
Over the last 2 decades, the prevalence has dropped
to 1 in 2,000, likely the result of detection of milder
cases of hypothyroidism.
2 : 1 female : male ratio.
5. Etiologic Classification of Congenital
Hypothyroidism
A. Primary Hypothyroidism
1.Defect of fetal thyroid development (dysgenesis) The most common cause of
permanent congenital hypothyroidism, accounting for 80-85% of cases
mostly without goiter
• Aplasia
• Hypoplasia
• Ectopia
2.Defective Synthesis of Thyroxine (Dyshormonogenesis) account for 15% of cases
A goiter is almost always present.
3. TSH unresponsiveness
4. Iodine deficiency (endemic goiter)
5.Maternal medications
Iodides, amiodarone , Propylthiouracil, methimazole, Radioiodine
B. CENTRAL (HYPOPITUITARY) HYPOTHYROIDISM
6. Clinical Manifestations
In neonatal period :
Most infants with congenital hypothyroidism
are asymptomatic at birth, even if there is
complete agenesis of the thyroid gland. This is
due to partial transplacental passage of
maternal T4, which provides fetal levels that
are approximately 33% of normal at birth.
7. Clinical Manifestations
Birthweight and length are normal, but head size may be
slightly increased because of myxedema of the brain.
The anterior and posterior fontanels are open
widely; observation of this sign at birth can serve as an initial
clue to the early recognition of congenital hypothyroidism.
( Only 3% of normal newborn infants have a posterior fontanel
larger than 0.5 cm )
8. Clinical Manifestations
Prolongation of physiologic jaundice ( >3 weeks ) ,caused by
delayed maturation of glucuronide conjugation, may be the
earliest sign
Feeding difficulties, lack of interest, somnolence, and choking
spells during nursing, are often present during the 1st mo of
life.
Respiratory difficulties, partly caused by the large tongue,
include apneic episodes, noisy respirations, and nasal
obstruction.
9. Clinical Manifestations
Affected infants cry little,
sleep much, have poor
appetites
There may be constipation
that does not usually
respond to treatment. The
abdomen
is large, and an umbilical
hernia is usually present.
10. Clinical Manifestations
The temperature is subnormal, often <35°C (95°F), and the
skin, particularly that of the
extremities, may be cold and mottled.
Edema of the genitals
The pulse is slow, and heart murmurs, cardiomegaly, and
asymptomatic pericardial effusion are common.
Macrocytic anemia is often present and is
refractory to treatment with hematinics.
11. Clinical Manifestations
Approximately 10% of infants with congenital
hypothyroidism have associated congenital
anomalies. Cardiac anomalies are most common,
but anomalies of the nervous system and eye have
also been reported.
Infants with congenital hypothyroidism may have
associated hearing loss
12. Clinical Manifestations
by 3-6 mo of age the clinical
picture is fully developed
• If congenital hypothyroidism
goes undetected and untreated,
these manifestations progress.
Retardation of physical and
mental development becomes
greater during the following
months,
13. Clinical Manifestations
stunted
The child’s growth
short
the extremities
normal or even increased
the head size
appear far apart
The eyes
swollen
the eyelids
is kept open
The mouth
Thick and protrude
The tongue
delayed
Dentition
dry and scaly &
Myxedema in the skin of
the eyelids, the back of the
hands, and the external
genitals.
The skin
Delayed
Development
is hoarse
The voice
14. Clinical Manifestations
• The muscles are usually hypotonic, but in rare
instances generalized muscular
pseudohypertrophy occurs (Kocher-Debré-
Sémélaigne syndrome).
• Affected older children can have an athletic
appearance because of pseudohypertrophy,
particularly in the calf muscles. Its pathogenesis is
unknown;
15. Laboratory Findings
• In developed countries, infants with congenital
hypothyroidism are identified by newborn screening
programs.
• Blood obtained by heel prick between 2 and 5 days of life
• Measure of levels of T4, followed by measurement of TSH
when T4 is low. This approach identifies infants with primary
hypothyroidism, some with central hypothyroidism, and
infants with a delayed elevation in TSH levels
16. Laboratory Findings
Serum levels of T4 or free T4 are low;
In primarily hypothyroidism, levels of TSH are elevated, often to
>100 mU/L.
Serum levels of thyroglobulin are usually low in infants with thyroid
agenesis or defects of thyroglobulin synthesis or secretion,
whereas they are elevated with ectopic glands and other inborn
errors of T4 synthesis, but there is a wide overlap of ranges.
Serum level of T3 maybe normal and not helpful in the diagnosis
17. Imaging
• Retardation of osseous
development can be shown
radiographically at birth in
approximately 60% of
congenitally hypothyroid
infants and indicates some
deprivation of thyroid hormone
during intrauterine life.
• The distal femoral and proximal
tibial epiphyses, normally
present at birth, are often
absent in congenital
hypothyroidism
The distal femoral and proximal tibial
epiphyses are absent
19. Treatment
• Levothyroxine (L-T4) given orally is the treatment of choice.
• The recommended initial starting dose is 10-15 µg/kg/day
(totaling 37.5-50.0 µg/day for most term infants).
• The dose of L-T4 on a weight basis gradually decreases with
age
• Because 80% of circulating T3 is formed by
monodeiodination of T4, serum levels of T4 and T3 return
to normal with L-T4 treatment alone.
20. MONITORING
Levels of serum T4 or free T4 and TSH should be
monitored at recommended intervals (every 1-2
mo in the 1st 6 mo of life, and then every 2-4 mo
between 6 mo and 3 yr of age).
The goals of treatment are to maintain the serum
free T4 or total T4 in the upper half of the
reference range for age with serum TSH in the
reference range for age, optimally 0.5-2.0 mU/L.
21. Prognosis
If therapy is initiated within the first month after birth
the prognosis for normal intellectual development is
excellent
If therapy is started after 6 months when signs of severe
hypothyroidism are present the intellectual function is
markedly decreased
Early diagnosis and adequate treatment from the 1st
weeks of life result in normal linear growth and
development.
