Workup for Congenital Hypothyroidism
All newborns should undergo screening for congenital hypothyroidism, and when screening is abnormal, immediately confirm the diagnosis with serum TSH and free T4 or total T4 levels, then initiate treatment without delay. 1, 2
Newborn Screening Approach
- Primary TSH screening is the most specific method and is standard in many programs worldwide, though some centers use primary T4 with backup TSH or combined approaches 3, 4
- Blood spot samples should be obtained after 24 hours of age to minimize false positives from the physiological neonatal TSH surge that occurs in the first 1-2 days after birth 3
- TSH screening detects primary hypothyroidism but will miss central (secondary/tertiary) hypothyroidism, which requires T4-based screening 5, 4
Confirmatory Testing
When screening is abnormal, confirm the diagnosis by measuring serum TSH and free T4 (or total T4) - an elevated TSH with low T4/free T4 confirms primary congenital hypothyroidism 1, 2, 6
Essential Initial Laboratory Tests:
- Serum TSH - elevated in primary hypothyroidism 1, 2
- Serum free T4 or total T4 - low in hypothyroidism 1, 2
- These confirmatory tests should be obtained urgently, ideally within days of abnormal screening 2, 6
Additional Diagnostic Studies (Optional, Do Not Delay Treatment)
While the following tests may help identify the underlying etiology, treatment should be initiated immediately without waiting for these results 2, 4:
- Thyroid radionuclide uptake and scan (using 99mTc or 123I) - most accurate test to distinguish thyroid dysgenesis from dyshormonogenesis 4
- Thyroid ultrasonography - nearly as accurate as scintigraphy but may miss ectopic thyroid tissue 4
- Serum thyroglobulin - helps differentiate athyreosis from ectopic thyroid 2, 4
- Maternal TRB-Ab (thyrotropin receptor blocking antibody) - if transient maternal antibody-mediated hypothyroidism is suspected 4
Special Populations Requiring Genetic Testing
For newborns with congenital hypothyroidism plus hypotonia, genetic testing for NKX2.1 (thyroid transcription factor) mutations or deletions is strongly recommended 7
This specific combination suggests Brain-Lung-Thyroid syndrome and warrants immediate genetic evaluation 7
Clinical Evaluation
When clinical signs suggest hypothyroidism, measure serum TSH and free T4 regardless of newborn screening results, as hypothyroidism can be acquired after screening or screening may have been falsely negative 5, 6
Key Clinical Signs to Assess:
- Large posterior fontanelle 6
- Macroglossia (large tongue) 2, 6
- Umbilical hernia 2, 6
- Prolonged jaundice 2, 6
- Constipation 2, 6
- Lethargy and decreased activity 2, 6
- Hypothermia 6
- Myxedematous facies 2
- Hypotonia 2
- Distended abdomen 2
Critical Timing Considerations
Treatment must be initiated within the first 2 weeks of life to prevent intellectual disability - the goal is to rapidly normalize thyroid function to minimize central nervous system exposure to hypothyroidism 3, 5
Common Pitfalls:
- Do not delay treatment waiting for imaging studies or etiology determination - these can be performed after treatment initiation 2, 4
- Do not dismiss transient TSH elevations - all infants with elevated TSH should be treated as having congenital hypothyroidism for the first 3 years of life, with reevaluation after age 3 3
- Early hospital discharge increases false positive rates - maintain high clinical suspicion and low threshold for confirmatory testing 3
- Normal newborn screening does not exclude hypothyroidism - clinical judgment supersedes screening results when symptoms are present 5, 6
Treatment Initiation
Levothyroxine 10-15 mcg/kg/day is the recommended starting dose, with the goal of rapidly raising serum T4 above 130 nmol/L (10 mcg/dL) and normalizing TSH 2, 5, 4
Monitor closely in the first 2 weeks for cardiac overload and arrhythmias, particularly in infants with severe hypothyroidism 8