Congenital Hypothyroidism in Pediatrics

1. Definition

2. Epidemiology

• Incidence: 1 in 2,000–4,000 live births (older estimates were 1:7,000 before widespread screening)
• Higher incidence in Asians and Hispanics compared to whites and blacks
• More common in preterm infants and with advanced maternal age
• Developmental thyroid abnormalities are twice as common in girls
• 10% of children with CH have other congenital birth defects; of those, 50% have congenital heart defects

3. Classification

A. Primary CH (Thyroid Gland Defect)

• Thyroid agenesis (complete absence)
• Ectopic thyroid (failure to descend normally during embryologic development)
• Thyroid hypoplasia

B. Central (Secondary/Tertiary) CH

• Deficiency of TSH or TRH
• Due to abnormal hypothalamic–pituitary development
• Occurs in 1 in 25,000–50,000 newborns

C. Transient CH

• Inadequate maternal iodine intake (endemic iodine deficiency — most common)
• Maternal antithyroid drug therapy during pregnancy
• Transfer of maternal TSH-R blocking antibodies (transplacental)
• Maternal iodine excess (e.g., amiodarone)
• Liver hemangiomas (increased deiodinase 3 production)
• Genetic defects

4. Pathophysiology

• Transplacental passage of maternal thyroid hormone provides partial hormonal support to the fetus before fetal thyroid function begins — this is why many affected newborns appear normal at birth.
• Once this maternal supply is cut after birth, thyroid hormone deficiency becomes manifest.
• Thyroid hormones are essential for:
  • Brain myelination and maturation (critical period: 0–3 years)
  • Bone maturation and linear growth
  • Metabolic rate regulation

5. Clinical Features

Early Signs (first weeks of life) — often subtle

• Lethargy, increased sleep
• Prolonged neonatal jaundice (>2 weeks)
• Myxedematous facies (puffy face, periorbital edema)
• Large anterior fontanelle (delayed closure)
• Macroglossia (large tongue)
• Hypothermia
• Hypotonia (floppy infant, "frog-leg" posture)
• Distended abdomen

Late Signs (if untreated)

• Poor sucking → feeding difficulties
• Constipation
• Hoarse cry
• Umbilical hernia
• Growth retardation (dwarfism)
• Developmental delay with cognitive retardation
• Myxedema (non-pitting skin thickening due to glycosaminoglycan deposition)
• Decreased activity

6. Classic Clinical Images

3-month-old infant showing myxedematous facies, macroglossia, generalized hypotonia, protuberant abdomen, and umbilical hernia.

Classic multisystemic manifestations: sparse hair, periorbital edema, macroglossia (face); frog-leg hypotonia and umbilical hernia (body).

7. Diagnosis

Newborn Screening (Mandatory)

• Mandated in all 50 US states; performed worldwide in industrialized nations
• Performed on day 2–5 of life (heel prick blood spot on filter card)
• Methods vary by program:
  • TSH-first (most common): reflex T4 if TSH elevated → cannot detect central hypothyroidism
  • T4-first: reflex TSH if T4 low
  • Combined TSH + T4 ± Tg: best for differentiating subtypes
• 1 in 25 abnormal screening tests is confirmed as true CH
• A second screen at 2–6 weeks is routinely done in some programs (for preterm/sick infants who may have delayed TSH rise)

Confirmatory Testing (Serum)

• TSH — elevated in primary CH
• Free T4 (FT4) or total T4 — low
• Results must be compared against age-appropriate reference intervals (thyroid hormones + TSH are physiologically higher in the first days of life)

Additional Investigations

• Radionuclide thyroid scan (Tc-99m or I-123): detects ectopic thyroid, absent gland
• Thyroid ultrasound: structural assessment
• Serum thyroglobulin (Tg): helps classify subtype
• Thyroid antibodies (maternal TSH-R blocking antibodies)
• Bone age X-ray: delayed skeletal maturation

Important: Additional investigations should NOT delay the initiation of treatment.

8. Treatment

Drug of Choice: Levothyroxine (L-T4)

Pediatric Dosing (Harriet Lane Handbook, 23rd Ed.):

• If risk of cardiac failure: start with lower dose (25 mcg/day)
• If T4 very low (<5 mcg/dL): use higher dose (12–17 mcg/kg/day)
• IV/IM dose = 50–75% of oral dose

Key Points on Treatment

• Levothyroxine can prevent mental retardation in >90% of children if commenced within the first 2 weeks of life
• For central hypothyroidism: document normal ACTH/cortisol function first before starting levothyroxine (risk of precipitating adrenal crisis if ACTH deficiency coexists)
• Transient CH resolves within weeks–months, but permanent CH needs lifelong replacement

Monitoring

• T4 and TSH: 1–2 weeks after initiation, then every 2 weeks until TSH normalizes
• Once stable: every 1–3 months (first year) → every 2–4 months (until age 3) → every 3–12 months (until growth complete)
• Recheck 4–6 weeks after any dose change
• Treated patients remain at risk for developmental delay — neurodevelopmental follow-up is essential

Adverse Effects of Overtreatment

• Craniosynostosis in infants
• Premature closure of epiphyses
• Pseudotumor cerebri
• Slipped capital femoral epiphysis

9. Genetic Causes (Selected)

10. Summary Table