Can high doses of Thyronorm (levothyroxine) for 45 days cause craniosynostosis in a baby with elevated Free Thyroxine (FT4) levels and suppressed Thyroid-Stimulating Hormone (TSH) levels?

High-Dose Levothyroxine and Risk of Craniosynostosis

Yes, high doses of levothyroxine (Thyronorm) causing suppressed TSH (0.016) and elevated FT4 (35, above normal range of 8-23) for 45 days can cause craniosynostosis in an infant who has not undergone complete closure of the fontanelles. 1

Mechanism and Evidence

• Overtreatment with levothyroxine in infants may result in craniosynostosis, particularly in those who have not undergone complete closure of the fontanelles 1
• Iatrogenic hyperthyroidism (as evidenced by suppressed TSH of 0.016 and elevated FT4 of 35) is a known risk factor for premature fusion of cranial sutures 2
• It is postulated that craniosynostosis occurs as a result of iatrogenic hyperthyroidism during a critical period of skull growth 2
• Studies have shown that maternal thyroid disease and thyroid dysfunction are associated with increased risk of craniosynostosis in offspring 3, 4

Clinical Significance and Risk Assessment

• The FDA drug label for levothyroxine specifically lists craniosynostosis as an adverse reaction in pediatric patients receiving levothyroxine therapy when overtreatment occurs 1
• The current clinical scenario shows clear evidence of overtreatment:
  • Initial TSH >40 treated with 37.5 mcg of levothyroxine daily
  • After 45 days, TSH suppressed to 0.016 (well below normal range)
  • FT4 elevated to 35 (above normal range of 8-23) 1
• This degree of thyroid hormone excess for 45 days represents a significant risk period during critical infant development 2

Management Recommendations

• Immediate dose adjustment is necessary to normalize thyroid function and minimize risk 5
• For infants with suppressed TSH and elevated FT4, the levothyroxine dose should be reduced 1
• Monitor TSH and free T4 levels at 4-6 week intervals after dose adjustment until values normalize 1
• The goal of therapy should be to normalize the serum TSH level and maintain FT4 within the normal range 1
• Close monitoring of head circumference and fontanelle closure is warranted given the exposure that has already occurred 1

Common Pitfalls to Avoid

• Continuing the current dose despite abnormal thyroid function tests would further increase risk of craniosynostosis and other complications of hyperthyroidism 1
• Completely stopping levothyroxine could lead to hypothyroidism, which carries its own risks for development 5
• Failure to monitor both TSH and FT4 during dose adjustments may lead to inadequate management of thyroid status 1
• Adjusting doses too frequently before reaching steady state (should wait 4-6 weeks between adjustments) can lead to unstable thyroid levels 5

Long-term Considerations

• Even after normalizing thyroid function, the infant should be monitored for signs of craniosynostosis, as some damage may have already occurred during the period of overtreatment 1
• Regular assessment of growth and development is essential in infants receiving thyroid hormone therapy 1
• The general aim of therapy is to normalize the serum TSH level and maintain FT4 within the normal range 1