Congenital hypothyroidism

Dr. MOHAMED A ALFAKI

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

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 .

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.

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

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 agentsD- iodine deficiency

2-secondary hypothyroidism -TSH deficiency.

3-tertiary hypothyroidism –TRH deficiency.

Sometimes may be associated with other hormone deficiencies.

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) .

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.

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.

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 .

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.

Clinical presentation:risk factors-family history, birth defects, female gender, GA> 40 weeks.Presentation can be classified as1-early presentation.2-late presentation.

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 .

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

Investigations:

Thyroid hormone assayNeonatal screening programs1-North America T4 with TSH backup2-European and Japanese based on measurement of TSHspecial care should be given to normal values according to age of neonate.

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.

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

Perchlorate discharge testthyroglobulin levelECGEEGPMRSserum cholesterol (older age)

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.

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

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 .