Congenital hypothyroidism is the most common neonatal metabolic disorder and can cause severe physical and neurological impairment if left untreated. It occurs in approximately 1 in 3,000-4,000 births. The thyroid gland normally develops between weeks 3-7 of gestation and begins secreting hormones around week 12. After birth, there is a surge in TSH levels in response to cooling which returns to normal after 3 days. Congenital hypothyroidism can be primary, from defects in the thyroid gland itself, or secondary, from deficiency in TSH. The most common cause is developmental defects of the gland such as hypoplasia or aplasia. Treatment involves lifelong levothyroxine replacement therapy.

1. Congenital hypothyroidism
Dr. MOHAMED A ALFAKI

2. Congenital hypothyroidism is the most
common neonatal metabolic disorder and
results in severe physical and
neurodevelopmental impairment and
infertility if untreated.
The incidence 1:3000-4000.

3. Around third week the thyroid gland develops as
epithelial proliferation between body and root of
the tongue- foramen cecum. It descends as
bilobed diverticulum in front of pharyngeal gut
still connected to it by the thyroglossal duct
(disappear later).
Migration continues to the definitive position in
front of the trachea by 7 week.

4. The gland started to secrete hormone around 12
week. Maternally T4 crosses the placenta in
physiologically significant amounts, which
explains the relatively normal phenotype in
hypothyroid infants.
After birth there is an acute discharge of TSH
provoked by cooling -peak at 30 min, return to
normal after 3 days.

5. Thyroid hormone increase oxygen
consumption, stimulate protein synthesis,
influence growth and maturation and
affects carbohydrate, lipid and vitamins
metabolism

6. Classification of congenital hypothyroidism:
1-primary where the problem arises from the gland
itself.
A- developmental defects.
B- inborn errors of thyroid hormone synthesis.
C- maternal exposure to specific agents
D- iodine deficiency

7. 2-secondary hypothyroidism -TSH deficiency.
3-tertiary hypothyroidism –TRH deficiency.
Sometimes may be associated with other
hormone deficiencies.

8. Developmental defects:
most common cause of congenital
hypothyroidism accounts for approximately 85%.
These defects may be hypoplasia of the gland or
compete aplasia.
Sometimes abnormally located gland (ectopic).

9. Ectopic gland is the most common form of
thyroid dysgenesis.
Its almost two third of developmental
disorders.
Sometimes can discovered later either when
fails to maintain adequate secretion of
hormone or appears as swelling along the
tract.

10. Exact cause is not known but familial cases
occasionally reported.
Three transcription factors (TTF-1,FOXE1,PAX-8)
are important for thyroid morphogenesis,
mutation in these factors can lead to thyroid
dysgenesis.
NKX2.1 found in both thyroid and CNS these
children expressed hypothyroidism and persistent
neurological problems despite early treatment.
Pendred syndrome due to sulfate transport
protein common to thyroid and cochlea.

11. Inborn errors of thyroid hormone synthesis :
autosomal recessive inheritance.
second commonest cause accounting for about
10% of identified cases by screening.
Presence of goiter at birth is strongly suggestive
but may develop later.
A defect may occur at any biosynthetic step.

13. Iodide transport defects due to mutation in
sodium iodide symporter.
Peroxidase deficiency most common defect
important in organification and coupling.
Thyroglobulin synthesis.
deficiency in deiodination.
Thyroid hormone transportation and
unresponsiveness also play role.

14. Clinical presentation:
risk factors-family history, birth defects, female
gender, GA> 40 weeks.
Presentation can be classified as
1-early presentation.
2-late presentation .

15. Early presentation:
prolonged gestation, LGA, large fontanelles.
Respiratory distress syndrome, delayed bone age,
umbilical hernia and goiter.
By 2 weeks: hypotonia, lethargy, constipation,
hypothermia, prolonged jaundice, mottling,
abdominal distension, feeding difficulties.

17. Late presentation:
classically appears after 6 weeks and include
puffy eye lids, coarse hair, large tongue,
myxedema, and hoarse cry. In borderline cases
presentation may be significant hearing
impairment and speech delay.

18. Investigations:
Thyroid hormone assay
Neonatal screening programs
1-North America T4 with TSH backup
2-European and Japanese based on measurement
of TSH
special care should be given to normal values
according to age of neonate.

19. Imaging:
retardation of osseous development can be seen
in up to 60% of affected infants.
In undetected or untreated patients discrepancy
between chronological age bone age increases.

21. Ultrasonography and Scintigraphy:
ultrasonographic examination is helpful
but may miss some ectopic glands.
Scintigraphy can pinpoint the underline cause.
123I sodium iodide is preferred.
Treatment should not be delayed for this study.

23. Perchlorate discharge test
thyroglobulin level
ECG
EEG
PMRS
serum cholesterol (older age)

24. Treatment:
levothyroxine is the treatment of choice.
80% of circulating T3 is formed from T4 and same
in the brain.
Recommended dose between 10-15 microg.
Severe manifestation MAX dose.
Thyroxine tabs should not be mixed with soy
protein formulas or iron.
T4 and TSH should be followed regularly.

25. If suspicion of transient hypothyroidism is
there discontinuation of therapy for 3-4
weeks can be tried at age of three.

26. Prognosis:
mainly depend on early diagnosis, rapid
correction of hypothyroxinemia,and compliance
to therapy in the first 2-3 years.
If proper management started early thase
children have normal linear growth and
intelligence.
Severely affected ones may experience
developmental problems.