What is the recommended management for neonates and infants with congenital or neonatal hypothyroidism?

Management of Neonatal and Congenital Hypothyroidism

Immediate Treatment Initiation

Initiate levothyroxine immediately upon diagnosis at 10-15 mcg/kg/day, ideally within the first 2 weeks of life, to prevent irreversible cognitive impairment. 1, 2

• Treatment must begin as soon as congenital hypothyroidism is confirmed by elevated TSH and low thyroid hormone levels—do not delay for additional diagnostic workup such as ultrasonography or scintigraphy 3
• The FDA label emphasizes that rapid restoration of normal serum T4 concentrations is essential for preventing adverse effects on cognitive development and overall physical growth 2
• Starting therapy within the first 2 weeks of life achieves nearly normal intelligence and growth outcomes, with >90% of children avoiding mental retardation 1, 3, 4

Screening Protocol

• Universal newborn screening using TSH testing with monoclonal antibodies should be performed on all infants 5
• Measure both TSH and free T4 for suspected cases 5
• Confirm diagnosis promptly with serum TSH and free thyroxine measurements by 4 weeks of age when possible 6

Treatment Goals and Monitoring

Target serum TSH <5 mIU/L and maintain free T4 or total T4 in the upper half of the age-specific reference range during the first 3 years of life. 7

• Serum total and free thyroxine normalize within 1 week of starting therapy at appropriate doses 6
• Monitor infants closely during the first 2 weeks of levothyroxine therapy for cardiac overload and arrhythmias 2
• Frequent evaluations are necessary to ensure optimal dosing and compliance 4
• Levothyroxine is generally continued for life in these patients 2

Special Diagnostic Considerations

For newborns presenting with the triad of congenital hypothyroidism, hypotonia, and respiratory symptoms (childhood interstitial lung disease), perform genetic testing for NKX2.1 (thyroid transcription factor) mutations or deletions. 8, 1

• The American Thoracic Society strongly recommends this testing because NKX2.1 mutations cause a characteristic triad of hypothyroidism, respiratory disease, and neurologic abnormalities 8, 1
• Benefits of identifying these mutations include avoiding surgical lung biopsy risks, facilitating family counseling about potential familial disease, and enabling anticipatory monitoring for neurological symptoms 8
• Genetic counseling should be offered to families when dominant mutations like NKX2.1 are identified 1

Clinical Pitfalls to Avoid

• Never rely solely on normal newborn screening results if clinical symptoms are present—hypothyroidism can be acquired after newborn screening, and physicians must maintain clinical judgment 4
• Clinical symptoms warranting thyroid function testing regardless of screening results include: large posterior fontanelle, macroglossia, umbilical hernia, prolonged jaundice, constipation, lethargy, and hypothermia 9
• Do not delay treatment initiation while pursuing etiology determination (thyroid dysgenesis vs. dyshormonogenesis)—this can be established later without compromising outcomes 3
• Infants with dyshormonogenesis show more sensitive TSH suppression response to initial therapy compared to those with thyroid dysgenesis, but both groups achieve euthyroidism with standard dosing 6

Dosing Considerations by Etiology

• The standard dose of 10-14 mcg/kg/day safely and effectively restores clinical and biochemical euthyroidism in both thyroid dysgenesis and dyshormonogenesis 6
• Despite similar severity at diagnosis, infants with dyshormonogenesis may require closer TSH monitoring due to their more sensitive response to replacement therapy 6