What is the management for a neonate with congenital hypothyroidism (elevated Thyroid-Stimulating Hormone (TSH)) and a TSH level of 60, who is asymptomatic?

Management of Neonatal Screening TSH 60 in Asymptomatic Neonate

Initiate levothyroxine therapy immediately at 10-15 mcg/kg/day without waiting for confirmatory testing, as a TSH of 60 mIU/L in a neonate strongly indicates congenital hypothyroidism and delays in treatment beyond 2 weeks of age can result in irreversible neurocognitive impairment. 1, 2, 3

Immediate Treatment Protocol

• Start levothyroxine at 10-15 mcg/kg/day orally as soon as the screening result is available, ideally within the first 2 weeks of life 4, 2, 5, 6
• Do not delay treatment to obtain additional diagnostic tests such as thyroid ultrasound, scintigraphy, or thyroglobulin levels, as these can be performed after therapy initiation 5, 7
• The absence of clinical symptoms does not justify delaying treatment, as more than 95% of infants with congenital hypothyroidism have few or no clinical manifestations at birth due to transplacental passage of maternal thyroid hormone 2, 7

Confirmatory Testing Before First Dose

• Obtain serum TSH and free T4 (or total T4) to confirm the diagnosis before administering the first dose of levothyroxine, but do not wait for results if they will delay treatment beyond 24-48 hours 2, 3
• An elevated serum TSH with low T4 or free T4 confirms primary congenital hypothyroidism 2, 3

Treatment Goals and Monitoring

• The immediate goal is to rapidly raise serum T4 above 130 nmol/L (10 mcg/dL) and normalize serum TSH levels 2
• Target free T4 or total T4 in the upper half of the age-specific reference range during the first 3 years of life 3, 7, 6
• Maintain serum TSH <5 mIU/L to ensure optimal neurocognitive development 7

Monitor TSH and free T4 every 1-2 months during the first 6 months of life, then every 3-4 months thereafter until age 3 years. 2

• Measure TSH and free T4 at 2 and 4 weeks after initiation of treatment 4
• Check levels 2 weeks after any dosage change 4
• After dosage stabilization, monitor every 3-12 months depending on age and clinical stability 4

Special Monitoring Considerations for Neonates

• Closely monitor infants during the first 2 weeks of levothyroxine therapy for cardiac overload and arrhythmias, as rapid normalization of thyroid hormone can unmask cardiac issues 4
• For infants at risk for hyperactivity, consider starting at one-fourth the recommended full replacement dosage and increase weekly by one-fourth until full dose is reached, though this approach may delay optimal neurocognitive outcomes 4

Critical Pitfalls to Avoid

• Never delay treatment waiting for imaging studies or subspecialty consultation, as every day of delay increases the risk of permanent neurocognitive impairment 5, 3
• Do not dismiss the screening result based on absence of clinical symptoms, as the classic signs of hypothyroidism (myxedematous facies, large fontanelles, macroglossia, umbilical hernia, hypotonia) are often absent or subtle in the neonatal period 2, 7
• Failure of serum T4 to increase into the upper half of normal range within 2 weeks, or failure of TSH to decrease below 20 IU/L within 4 weeks, indicates inadequate therapy and requires dose adjustment 4
• Avoid underdosing, as starting doses lower than 10-15 mcg/kg/day are associated with worse neurocognitive outcomes 2, 3

Prognosis and Long-term Management

• When treatment is initiated within the first 2 weeks of life with adequate dosing, more than 90% of children with congenital hypothyroidism achieve normal neurocognitive development with IQs similar to sibling or classmate controls 2, 5, 6
• Infants started on treatment after 30 days of age or on lower initial doses have demonstrably worse neurocognitive outcomes 2
• Levothyroxine is generally continued for life in patients with permanent congenital hypothyroidism 4

Etiology Determination (After Treatment Initiation)

• Thyroid dysgenesis accounts for 85% of permanent primary congenital hypothyroidism 2, 7
• Dyshormonogenesis (inborn errors of thyroid hormone biosynthesis) accounts for 10-15% of cases 2, 7
• Thyroid ultrasound, radionuclide uptake and scan, or serum thyroglobulin can help identify the underlying cause but should not delay treatment 2, 5