What is the initial investigation protocol for suspected thyroid dysfunction in newborns?

Thyroid Investigation Protocol in Newborns

The initial investigation for suspected thyroid dysfunction in newborns should include thyroid stimulating hormone (TSH) measurement from blood samples, with succinylacetone (SA) as a primary marker for tyrosinemia type 1, followed by confirmatory testing with free T4 levels when indicated.

Initial Screening

Blood Sample Collection

• Timing options:
  • Cord blood at birth (sensitivity 100%, specificity 99.6%, recall rate 0.04%) 1
  • Heel-stick sample at 48-72 hours of age (sensitivity 100%, specificity 98.3%, recall rate 1.68%) 1
  • For preterm and low birth weight infants: screen at 48-72 hours postnatal age 2
  • For sick babies: screen by 7 days of age at the latest 2

Primary Screening Parameters

• TSH measurement is the recommended initial test for screening and evaluating suspected thyroid dysfunction 3
• Cutoff values for further investigation:
  • TSH > 20 mIU/L serum units (for samples taken at 48-72 hours)
  • TSH > 34 mIU/L for samples taken between 24-48 hours of age 2

Confirmatory Testing

For Markedly Elevated Screening TSH (>40 mIU/L)

• Immediate confirmatory venous blood tests:
  • Free T4 (FT4) or total T4
  • TSH 2

For Mildly Elevated Screening TSH

• Second screening TSH at 7-10 days of age 2

Diagnostic Criteria for Primary Congenital Hypothyroidism

• Venous confirmatory TSH >20 mIU/L before age 2 weeks
• Venous confirmatory TSH >10 mIU/L after age 2 weeks
• With low T4 (<10 μg/dL) or FT4 (<1.17 ng/dL) 2

Additional Testing When Indicated

For Suspected Genetic Causes

• For newborns with congenital hypothyroidism and hypotonia: genetic testing for NKX2.1 (thyroid transcription factor [TTF]) mutations or deletions 3
• For severe or rapidly progressive disease, or family history of thyroid disorders: consider testing for genetic abnormalities 3

For Suspected Tyrosinemia Type 1

• Blood succinylacetone (SA) should be used as the primary marker 3
• Tyrosine alone is not recommended as a primary marker (may miss 28% of cases) 3

Imaging Studies

• Thyroid imaging is recommended after biochemical confirmation of congenital hypothyroidism
• Options include:
  • Radionuclide scintigraphy (most accurate for detecting thyroid dysgenesis) 4
  • Thyroid ultrasonography 2
• Treatment should not be delayed while awaiting imaging results 2

Treatment Initiation

• Begin levothyroxine at 10-15 μg/kg daily immediately upon confirmation 5
• Goals of treatment:
  • Raise serum T4 rapidly into the normal range
  • Maintain free T4 in the upper half of the normal range
  • Keep TSH normal 4
  • Maintain normal growth and development 4

Monitoring Protocol

• Serum T4/FT4 at 2 weeks after treatment initiation
• TSH and T4/FT4 at 1 month
• Then every 2 months until 6 months of age
• Every 3 months from 6 months to 3 years
• Every 3-6 months thereafter 2

Common Pitfalls and Caveats

1. False negatives: Clinical symptoms of hypothyroidism (large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia) warrant thyroid testing regardless of screening results 5

2. False positives: Early discharge after birth may increase false positive TSH elevations due to physiological neonatal TSH surge 6

3. Transient hypothyroidism: All infants with elevated TSH should be treated as having congenital hypothyroidism for the first 3 years of life, with reevaluation at age 3 to assess the need for lifelong therapy 2

4. Siblings at risk: If a child is diagnosed with certain forms of thyroid dysfunction (like tyrosinemia type 1), siblings should be tested immediately 3

5. Delayed diagnosis consequences: Untreated congenital hypothyroidism leads to intellectual disabilities, emphasizing the importance of prompt screening and treatment 5