Congenital Hypothyroidism
Introduction to Congenital Hypothyroidism
Congenital hypothyroidism (CH) is a condition characterized by thyroid hormone deficiency present at birth. It is one of the most common preventable causes of intellectual disability. The incidence is approximately 1:2000 to 1:4000 newborns. Early diagnosis and treatment are crucial to prevent the severe developmental and growth delays associated with untreated CH.
Thyroid hormones play a vital role in normal brain development, especially during the first few years of life. They are essential for normal growth, neuronal differentiation, myelination of nerves, and cognitive development. The fetal thyroid gland begins to function around 10-12 weeks of gestation, but prior to this, the fetus is dependent on maternal thyroid hormones that cross the placenta.
Etiology of Congenital Hypothyroidism
Congenital hypothyroidism can result from various causes:
- Thyroid dysgenesis (85% of cases):
- Thyroid agenesis: Complete absence of thyroid tissue
- Thyroid hypoplasia: Underdeveloped thyroid gland
- Thyroid ectopy: Abnormal location of the thyroid gland
- Dyshormonogenesis (10-15% of cases): Defects in thyroid hormone synthesis, including:
- Sodium/iodide symporter defects
- Thyroid peroxidase deficiency
- Thyroglobulin deficiency
- Iodotyrosine deiodinase deficiency
- Central hypothyroidism (1% of cases): Due to pituitary or hypothalamic dysfunction
- Transient hypothyroidism: Can be caused by maternal factors such as iodine deficiency or excess, antithyroid medications, or transplacental passage of TSH receptor-blocking antibodies
Genetic factors play a role in many cases of CH, particularly in dyshormonogenesis. Mutations in genes such as TSHR, PAX8, NKX2-1, and FOXE1 have been associated with thyroid dysgenesis.
Clinical Presentation of Congenital Hypothyroidism
The clinical features of congenital hypothyroidism are often subtle and not present at birth due to the protective effect of maternal thyroid hormones. Symptoms typically develop gradually over the first few weeks to months of life. Common signs and symptoms include:
- Prolonged physiologic jaundice
- Feeding difficulties
- Constipation
- Lethargy and somnolence
- Hypotonia
- Large anterior fontanelle
- Macroglossia
- Umbilical hernia
- Dry, mottled skin
- Hypothermia
- Bradycardia
- Poor growth
- Hoarse cry
In severe cases or if left untreated, congenital hypothyroidism can lead to:
- Intellectual disability
- Developmental delays
- Short stature
- Delayed skeletal maturation
It's important to note that with widespread newborn screening programs, most cases of CH are diagnosed and treated before clinical signs become apparent.
Diagnosis of Congenital Hypothyroidism
Diagnosis of congenital hypothyroidism is primarily based on newborn screening tests and confirmatory thyroid function tests.
Newborn Screening:
- Most developed countries have implemented universal newborn screening programs for CH.
- Screening is typically done between 2-5 days of life using a heel-prick blood sample.
- The primary screening test measures thyroid-stimulating hormone (TSH) levels. Some programs also measure total or free T4.
- Elevated TSH (>20-25 mIU/L) or low T4 levels indicate the need for confirmatory testing.
Confirmatory Testing:
- Serum TSH and free T4 measurements
- Thyroid ultrasound to assess gland size and location
- Thyroid scintigraphy using technetium-99m or iodine-123 to evaluate thyroid gland position and size
- Thyroid peroxidase and thyroglobulin antibodies to rule out transient CH due to maternal antibodies
Additional Investigations:
- Thyroglobulin levels (useful in differentiating thyroid agenesis from ectopy)
- Urinary iodine measurement (to assess iodine status)
- Genetic testing for suspected hereditary cases
Early diagnosis and treatment initiation (ideally within the first 2 weeks of life) are crucial for optimal neurodevelopmental outcomes.
Treatment of Congenital Hypothyroidism
The primary treatment for congenital hypothyroidism is thyroid hormone replacement therapy. The goal is to normalize thyroid hormone levels as quickly as possible to ensure normal growth and development.
Levothyroxine Therapy:
- Levothyroxine (L-thyroxine) is the treatment of choice.
- Initial dosage: 10-15 μg/kg/day, typically given as a single daily dose.
- Administration: Tablets should be crushed and mixed with a small amount of water or breast milk. Avoid mixing with soy formula, iron, or calcium supplements.
- Treatment should be initiated as soon as the diagnosis is confirmed, ideally within the first two weeks of life.
Monitoring:
- Frequent monitoring of TSH and free T4 levels is essential:
- 2 and 4 weeks after treatment initiation
- Every 1-2 months during the first year of life
- Every 2-3 months between 1-3 years of age
- Every 3-12 months thereafter
- Dose adjustments are made based on these results, aiming to keep free T4 in the upper half of the normal range and TSH in the lower half of the normal range.
Long-term Management:
- Regular clinical assessments of growth, development, and school performance
- Bone age determinations to assess skeletal maturation
- Lifelong treatment is typically required, except in some cases of transient CH
- Re-evaluation of the diagnosis may be considered at 3 years of age in some cases, particularly in children with an in-situ thyroid gland
Patient and family education about the importance of adherence to treatment and regular follow-up is crucial for optimal outcomes.
Prognosis of Congenital Hypothyroidism
The prognosis for children with congenital hypothyroidism has improved dramatically with the implementation of newborn screening programs and early treatment initiation. However, outcomes can vary based on several factors:
Factors Influencing Prognosis:
- Timing of diagnosis and treatment initiation
- Severity of hypothyroidism at diagnosis
- Adequacy of treatment and compliance
- Etiology of CH
Neurodevelopmental Outcomes:
- With early and adequate treatment, most children achieve normal or near-normal cognitive development.
- Subtle neurocognitive deficits may persist in some children, particularly in areas of attention, memory, and visuospatial processing.
- Children with severe hypothyroidism at diagnosis or delayed treatment initiation are at higher risk for developmental delays.
Growth and Physical Development:
- Normal growth and puberty can be achieved with proper treatment.
- Final adult height is usually within the normal range, particularly if compliance with treatment is good.
Long-term Health Considerations:
- Increased risk of obesity and metabolic syndrome in some studies
- Potential for mild hearing impairment in a small percentage of patients
- Possible increased risk of cardiovascular abnormalities, particularly in those with thyroid dysgenesis
Regular follow-up throughout childhood and into adulthood is essential to optimize treatment, monitor for any complications, and ensure the best possible outcomes. With appropriate management, the vast majority of individuals with CH can lead normal, healthy lives.
