What is the first lab level to check in a neonate with elevated Thyroid Stimulating Hormone (TSH)?

First Lab Test After Elevated Neonatal TSH

Check both venous TSH and free T4 (or total T4) simultaneously as soon as possible after a positive newborn screen to confirm the result and differentiate between subclinical and overt hypothyroidism. 1

Diagnostic Algorithm

The confirmatory testing strategy requires obtaining both tests together rather than sequentially:

• Venous blood sampling is essential—do not rely solely on repeat heel-stick screening, as venous samples provide more accurate confirmation 1
• TSH measurement confirms whether the elevation is persistent and quantifies the severity 2, 3
• Free T4 (or total T4) measurement distinguishes between:
  • Overt congenital hypothyroidism: elevated TSH with low T4 (requires immediate treatment) 2, 4
  • Subclinical hypothyroidism: elevated TSH with normal T4 (treatment decisions based on TSH level and clinical context) 5, 6
  • Central hypothyroidism: low or inappropriately normal TSH with low T4 (rare but critical to identify) 2

Timing Considerations

• Obtain confirmatory testing as soon as possible after the positive screen to minimize delays in treatment initiation 1, 2
• Samples should ideally be collected after 24 hours of age to avoid false positives from the physiological TSH surge that occurs in the first 1-2 days after birth 4
• The goal is to rapidly normalize thyroid function if treatment is needed, as delayed treatment (>30 days) is associated with worse neurocognitive outcomes 2

Critical Interpretation Points

For TSH levels:

• TSH >20 mU/L with normal free T4 generally warrants treatment according to international guidelines 5
• TSH 20-30 mU/L represents a gray zone where treatment decisions depend on age at testing, TSH trend, and absolute free T4 level 5
• TSH >30 mU/L typically requires levothyroxine treatment 5

For free T4 levels:

• Age-specific reference intervals are critical—neonatal lower limits are considerably higher than adult ranges 3
• At day 3-7: normal range 20.5-37.1 pmol/L 3
• At day 13-15: normal range 15.3-26.5 pmol/L 3
• Free T4 in the lower half of the age-specific reference range, combined with elevated TSH, may indicate need for treatment even if technically "normal" 5

Common Pitfalls to Avoid

• Do not obtain TSH alone—you need free T4 simultaneously to properly classify the type and severity of thyroid dysfunction 1, 2
• Do not delay confirmatory testing waiting for symptoms to develop, as most neonates with congenital hypothyroidism appear normal at birth 2, 4
• Do not use adult reference ranges for free T4 interpretation in neonates, as this will miss cases of central hypothyroidism and misclassify severity 3
• Avoid treating based solely on screening results without venous confirmation, as false positives are common, especially with early discharge (<24 hours) and the physiological TSH surge 4

Additional Diagnostic Considerations

While not first-line tests, the following may help determine etiology after confirming the diagnosis:

• Thyroid ultrasound can identify dysgenesis and help distinguish transient from permanent hypothyroidism in borderline cases 5
• Serum thyroglobulin may help pinpoint underlying etiology 2
• These additional tests should not delay treatment initiation if TSH and T4 levels indicate clear hypothyroidism 2