What to do with a full-term baby with significantly elevated Thyroid-Stimulating Hormone (TSH) level, despite absence of symptoms?

Management of Full-Term Newborn with TSH of 60 mIU/L

Start levothyroxine immediately (Answer A) - treatment should be initiated as soon as possible, preferably within the first 2 weeks of life, to prevent irreversible neurocognitive damage from congenital hypothyroidism.

Rationale for Immediate Treatment

A TSH of 60 mIU/L in a newborn represents severe congenital hypothyroidism requiring urgent intervention, regardless of clinical appearance. 1

• More than 95% of infants with congenital hypothyroidism have few or no clinical manifestations at birth, making the absence of symptoms an unreliable indicator for treatment decisions 1
• Thyroid hormones are critical for early neurocognitive development, and prompt recognition and treatment is of utmost importance to optimize physical and neurodevelopmental outcomes 1
• Treatment in the first several weeks of life can result in nearly normal intelligence and growth, whereas delayed treatment leads to irreversible cognitive impairment 2

Treatment Protocol

Initial Levothyroxine Dosing

Start with 10-12.5 mcg/kg/day of levothyroxine - this range balances the need for rapid normalization while minimizing iatrogenic hyperthyroidism. 3, 4

• Doses of 7.5-8.0 mcg/kg/day normalize FT4 and FT3 at 15 days in 100% of cases and TSH at 2 months in 90% of cases 3
• However, starting doses >12.5 mcg/kg/day result in 57.1% of infants requiring dose reduction for iatrogenic hyperthyroxinemia, compared to 26.1% with doses ≤12.5 mcg/kg/day 4
• The FDA label confirms levothyroxine is indicated from birth for congenital hypothyroidism as replacement therapy 5

Monitoring Schedule

Check TSH and free T4 at 2 weeks, then at 4 weeks, then every 4-6 weeks during the first year to ensure adequate treatment without overtreatment. 3, 6

• Target TSH <5 mIU/L and maintain free T4 in the upper half of the age-specific reference range 1
• Infants should be closely monitored during the first 2 weeks for cardiac overload and arrhythmias 5
• Early assessment allows identification of the subgroup requiring higher doses (those with more profound hypothyroidism) 3

Critical Pitfalls to Avoid

Do NOT Delay Treatment

Waiting to reassess in 1 month (Answer B) or observing for symptoms (Answer C) will result in preventable neurocognitive damage. 1

• The window for preventing intellectual disability is narrow - treatment must begin within the first 2 weeks of life 1
• Untreated congenital hypothyroidism leads to cretinism (growth failure, mental retardation, and other neuropsychologic defects) 2
• TSH of 60 mIU/L far exceeds any threshold for observation - even TSH >10 mIU/L warrants treatment in adults 2

Avoid Both Under- and Over-Treatment

The risk of overtreatment exists but should not prevent immediate initiation of therapy. 6, 4

• Approximately 20-25% of treated infants show evidence of overtreatment after 12 months, but this is manageable with dose adjustments 6
• The risk of undertreatment (permanent cognitive impairment) far outweighs the risk of temporary overtreatment (which can be corrected with monitoring) 1
• Starting at the lower end of the recommended range (10-12.5 mcg/kg/day rather than 15 mcg/kg/day) minimizes overtreatment risk while ensuring adequate therapy 4

Additional Considerations

Confirm the diagnosis with repeat TSH and free T4 measurement, but do not delay treatment while awaiting confirmatory results. 2

• Obtain thyroid ultrasound to evaluate for thyroid dysgenesis versus gland in situ, as this affects long-term prognosis 6
• Thyroid dysgenesis patients typically require higher doses and have permanent hypothyroidism 6
• Some cases of gland in situ may represent transient hypothyroidism, but this determination is made at 3 years of age during re-evaluation, not at diagnosis 6