What are the normal ranges for Thyroid Stimulating Hormone (TSH) and Free Thyroxine (FT4) levels in Downs syndrome infants?

Thyroid Function Test Ranges for Down Syndrome Infants

Infants with Down syndrome require both TSH and free T4 measurement simultaneously, as they frequently have elevated TSH levels (mean 7.0 mU/L vs 3.9 mU/L in controls) even at birth, and standard T4-based screening programs miss approximately 50% of cases with thyroid dysfunction. 1, 2

Normal Reference Ranges and Down Syndrome-Specific Considerations

TSH Levels in Down Syndrome Infants

• General population reference: TSH values below 0.1 mU/L are considered low and values above 6.5 mU/L are considered elevated 3
• Down syndrome infants show significantly higher baseline TSH: Mean TSH of 7.0 ± 7.45 mU/L compared to 3.9 ± 2.43 mU/L in controls, with males showing particularly elevated values 1
• TSH >5 mU/L warrants close monitoring: 27.7% of Down syndrome infants under 1 year have subclinical hypothyroidism with TSH between 5-12 mU/L 4
• TSH >12 mU/L indicates treatment threshold: This level, especially when combined with FT4 <9 pmol/L, requires levothyroxine therapy 4, 5

Free T4 Levels in Down Syndrome Infants

• Both TSH and FT4 must be measured together to distinguish primary hypothyroidism (elevated TSH with low FT4) from central hypothyroidism (low or normal TSH with low FT4) 3, 6
• FT4 <9 pmol/L is abnormal and requires treatment when present with elevated TSH 4
• Down syndrome infants have lower total T4 concentrations compared to the general population, making T4-based screening alone inadequate 2

Critical Screening Algorithm for Down Syndrome Infants

Timing of Thyroid Function Testing

• At birth (newborn screening): Initial TSH and T4 measurement 7
• 2 weeks of age: Repeat TSH and FT4 7
• 1 month of age: Additional screen (captures cases missed by newborn screening) 7
• 3 months of age: Another screen (identifies 22.2% of thyroid disorders by 90 days of life) 7
• 6 months and 12 months: Standard AAP guideline intervals 7
• Annually thereafter: Ongoing surveillance 7

Interpretation Categories

Group 1 - Normal Thyroid Function:

• TSH <5 mU/L with normal FT4 4
• Monitor annually 5

Group 2 - Subclinical Hypothyroidism:

• TSH 5-12 mU/L with normal FT4 4
• Monitor every 3 months 5
• Consider treatment if TSH 11-20 mU/L even with normal T4, as 25.3% benefit from low-dose thyroxine 5

Group 3 - Overt Hypothyroidism:

• TSH >12 mU/L and/or FT4 <9 pmol/L 4
• Initiate levothyroxine therapy immediately 4
• Rule out adrenal insufficiency before starting thyroid hormone replacement 6

Common Pitfalls and How to Avoid Them

Screening Method Failures

• T4-based screening programs miss 50% of congenital hypothyroidism cases in Down syndrome infants because they rely on initial T4 measurement followed by TSH only if T4 is low 2
• Always measure both TSH and FT4 simultaneously rather than sequential testing 2

Timing Errors

• Current AAP guidelines (birth, 6 months, 12 months) miss nearly 20% of cases: Additional screens at 1 and 3 months identify thyroid disorders at mean of 101-104 days before the scheduled 6-month screen would detect them 7
• 30% of Down syndrome infants develop thyroid disorders in the first year: 11% by 30 days, 17% by 60 days, and 22.2% by 90 days 7

Diagnostic Confusion

• Evaluating hypothyroidism symptoms is difficult in Down syndrome because slow speech, thick tongue, and slow mentation are typical findings in both conditions 3
• TSH elevation alone at newborn screening does not predict later thyroid dysfunction in childhood, requiring ongoing surveillance 1
• Low TSH with low FT4 indicates central hypothyroidism: Must evaluate for hypophysitis and check morning ACTH/cortisol before starting thyroid replacement 3, 6

Treatment Considerations

• Infants with TSH >12 mU/L show significantly lower BMI-SDS and benefit from treatment with improved growth parameters after 3 years of levothyroxine 4
• Even mild TSH elevation (11-20 mU/L) with normal T4 may warrant low-dose thyroxine therapy in Down syndrome infants 5
• Monitor FT4 every 6-8 weeks during dose adjustments, targeting FT4 in the upper half of normal range 6

Special Population Considerations

• Male infants with Down syndrome show particularly elevated TSH values at newborn screening 1
• 14.9% of Down syndrome infants under 1 year have hypothyroidism (10.6% primary, 4.3% secondary), compared to 12.7% in older children 4
• Thyroid antibody positivity occurs in 19% of infants and 47.3% of older children with Down syndrome 4