When can levothyroxin (thyroxine) be withdrawn in children with hypothyroidism?

Withdrawal of Levothyroxine in Children with Hypothyroidism

Levothyroxine can be withdrawn in children with congenital hypothyroidism after age 3 years through a 30-day trial period to determine if the hypothyroidism is permanent or transient. 1

Diagnostic Trial Protocol for Permanent vs. Transient Hypothyroidism

Standard 30-Day Withdrawal Approach (After Age 3)

• Discontinue levothyroxine completely for 30 days in children where permanent hypothyroidism has not been definitively established, but only after the child reaches at least 3 years of age 1
• Measure serum T4 and TSH at the end of the 30-day period 1
• If T4 is low AND TSH is high: diagnose permanent hypothyroidism and reinstitute levothyroxine therapy for life 1
• If T4 and TSH are both normal: the hypothyroidism was transient and treatment can remain discontinued 1
• If results are inconclusive, maintain careful follow-up with repeat thyroid function testing if any signs or symptoms of hypothyroidism develop 1

Alternative Dose-Reduction Approach (For Severely Affected Children)

• For children who may become clinically hypothyroid during complete withdrawal, reduce the levothyroxine dose by 50% for 30 days instead of complete discontinuation 1
• If TSH rises above 20 mU/L after 30 days: permanent hypothyroidism is confirmed—resume full replacement therapy 1
• If TSH remains ≤20 mU/L: discontinue levothyroxine completely for another 30 days, then repeat T4 and TSH 1

Special Population: Very Low Birth Weight (VLBW) Infants

• Thyroid dysfunction in VLBW infants is commonly transient, with most cases resolving by age 2 years 2
• Attempts to discontinue levothyroxine can begin around age 2 years or earlier when low maintenance doses have been achieved 2
• In one cohort of 39 VLBW infants taken off therapy at approximately 2 years, all successfully discontinued levothyroxine and maintained normal thyroid function 2
• Tc-99m thyroid scans showed no distinct abnormalities in 32 of these infants, supporting the transient nature of their hypothyroidism 2

Critical Monitoring During Withdrawal

• Maintain a high index of suspicion for relapse even after successful withdrawal 1
• Repeat thyroid function tests promptly if any signs or symptoms of hypothyroidism develop during follow-up 1
• Monitor for clinical manifestations including poor school performance, impaired concentration, slowed mentation, and reduced growth velocity 1

Why Age 3 Years Is the Threshold

• Brain maturation is largely complete by age 3, making the risk of neurodevelopmental consequences from temporary hypothyroidism during the trial period substantially lower 1
• Before age 3, even brief periods of hypothyroidism can adversely affect intellectual development and physical growth 1
• Congenital hypothyroidism requires rapid restoration of normal T4 concentrations to prevent adverse effects on intellectual development 1

Common Pitfalls to Avoid

• Never attempt withdrawal before age 3 years in children with congenital hypothyroidism, as this risks irreversible neurodevelopmental damage 1
• Do not assume hypothyroidism is permanent without performing a withdrawal trial after age 3, as some cases are transient 1
• Avoid inadequate follow-up after withdrawal—even successful discontinuation requires ongoing surveillance for late relapse 1
• In VLBW infants specifically, recognize that most hypothyroidism is transient and earlier withdrawal (around age 2) may be appropriate when maintenance doses are low 2

Distinguishing Permanent from Transient Hypothyroidism

• Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent congenital hypothyroidism cases, respectively 3
• Transient hypothyroidism is more common in VLBW infants and may be related to immaturity of the hypothalamic-pituitary-thyroid axis 2
• The withdrawal trial is the definitive method to distinguish permanent from transient disease after age 3 1