Treatment of Congenital Hypothyroidism in Infants
The treatment for congenital hypothyroidism in infants is immediate initiation of levothyroxine at a dosage of 10-15 mcg/kg/day orally, which should be started as soon as possible after diagnosis, preferably within the first 2 weeks of life. 1, 2
Diagnosis and Screening
- Newborn screening for congenital hypothyroidism is available throughout the United States and is essential for early detection 3
- More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations at birth 4
- When clinical symptoms are present (large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, hypothermia), measurement of serum TSH and free T4 is indicated regardless of screening results 2
Initial Treatment Protocol
Dosing
- Initial levothyroxine dosage: 10-15 mcg/kg/day orally 1, 2
- Higher initial doses (50 mcg/day or approximately 14.5 mcg/kg/day) provide more rapid normalization of TSH by 2 weeks 5
- Prompt initiation is critical - treatment should begin immediately upon diagnosis 1
Treatment Goals
- Maintain serum free T4 or total T4 within the upper half of the age-specific reference range 4
- Keep serum TSH < 5 mIU/L 4
- Eliminate all symptoms and signs of hypothyroidism 4
Monitoring and Dose Adjustment
- Serum T4 and free T4 concentrations should reach target range by 3 days of therapy with appropriate dosing 5
- TSH normalization should occur by 2 weeks with optimal dosing 5
- Target range during first 2 weeks of treatment:
- T4: 10-18 μg/dL
- Free T4: 2-5.0 ng/dL 5
- After 2 weeks of treatment, target range adjusts to:
- T4: 10-16 μg/dL
- Free T4: 1.6-2.2 ng/dL 5
Long-term Management
- Levothyroxine requirement progressively decreases during childhood 6
- For pre-school children: 3-4 μg/kg/day (70-90 μg/m²/day) 6
- For school-age children: 2-3 μg/kg/day (60-80 μg/m²/day) 6
- Dose requirements vary based on etiology:
- Children with in situ thyroid gland require lower doses than those with thyroid dysgenesis (athyreosis or ectopic gland) 6
Clinical Pearls and Pitfalls
- Rapid restoration of normal serum T4 concentrations is essential for preventing adverse effects on cognitive development, physical growth, and maturation 7
- Untreated congenital hypothyroidism leads to intellectual disabilities 2
- Treatment in the first several weeks of life can result in nearly normal intelligence and growth 3
- Closely monitor infants during the first 2 weeks of therapy for cardiac overload and arrhythmias 7
- Levothyroxine therapy is generally continued for life in these patients 7
Special Considerations
- Infants with dyshormonogenesis may have a more sensitive response to initial thyroid hormone replacement than patients with thyroid dysgenesis 8
- The levothyroxine dose at 6 months of age appears predictive of the requirement until 12 years of age 6
- Controversy remains regarding optimal management of special populations, including preterm or low-birth-weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism 2
Early diagnosis and prompt treatment of congenital hypothyroidism are crucial for optimal neurocognitive outcomes. With appropriate levothyroxine therapy initiated early in life, children with congenital hypothyroidism can achieve grossly normal neurocognitive outcomes in adulthood.