Hypothyroidism in Neonates and Children

Table of Contents(toc)

1. Definition

Hypothyroidism is a clinical state resulting from deficiency of thyroid hormone production or action, leading to a generalized slowing of metabolic processes.

It may be:

• Congenital (Neonatal) – present at birth.

• Acquired (Childhood) – develops later due to autoimmune, iatrogenic, or other causes.

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2. Classification

A. Based on Level of Defect

B. Based on Onset

• Congenital hypothyroidism (CH)

• Acquired hypothyroidism

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3. Epidemiology

• CH: ~1 in 2,000–4,000 live births.

• More common in females.

• Acquired form common in older children/adolescents, often autoimmune (Hashimoto’s).

thyroid gland

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4. Etiology

A. Congenital Hypothyroidism

1. Thyroid dysgenesis (80–85%)

   • Agenesis, ectopy, or hypoplasia.

   • Usually sporadic.

2. Dyshormonogenesis (10–15%)

   • Inborn errors of thyroid hormone synthesis (autosomal recessive).

   • E.g. TPO, TG, Pendrin, NIS mutations.

3. Central hypothyroidism (rare)

   • Pituitary/hypothalamic malformation, midline defects.

4. Transient CH

   • Iodine excess/deficiency, maternal antibodies or antithyroid drugs.

5. Thyroid hormone resistance – extremely rare.

B. Acquired Hypothyroidism

• Autoimmune thyroiditis (Hashimoto’s) – most common.

• Iodine deficiency/excess.

• Post-irradiation or post-surgical.

• Drugs: amiodarone, lithium, interferon-α.

• Secondary causes: pituitary tumors, craniopharyngioma.

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5. Pathophysiology

↓ Thyroid hormone → ↓ metabolic activity → impaired CNS myelination, growth retardation, delayed bone maturation.

• In neonates: irreversible neurodevelopmental impairment if untreated.

• In older children: growth failure and delayed puberty predominate.

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6. Clinical Features

A. Neonatal / Congenital

Often asymptomatic at birth due to transplacental maternal T4.

Typical features (develop over weeks):

• Prolonged jaundice

• Lethargy, hypotonia

• Feeding difficulty, constipation

• Large fontanelles

• Macroglossia

• Umbilical hernia

• Cold, dry skin

• Hoarse cry

• Poor growth

• Delayed bone age

• Delayed milestones (later)

B. Childhood / Acquired

• Growth retardation, short stature

• Weight gain with poor height velocity

• Fatigue, cold intolerance

• Constipation

• Dry skin, coarse hair

• Bradycardia

• Delayed puberty / menstrual irregularities

• Pseudoprecocious puberty (rare, due to high TRH → prolactin ↑)

• Goiter (especially in Hashimoto’s)

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7. Investigations

A. Screening

• Neonatal screening: heel-prick sample at 48–72 hr.

  • Primary TSH (most programs).

  • Elevated TSH → confirm with serum free T4.

B. Diagnostic Tests

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8. Complications (if untreated)

• Neurologic: irreversible intellectual disability, deaf-mutism, spasticity.

• Growth: severe stunting, delayed bone age.

• Metabolic: dyslipidemia.

• Cardiac: bradycardia, pericardial effusion.

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9. Management

A. Principles

• Early, adequate, lifelong replacement.

• Monitor and titrate carefully to maintain euthyroid state.

B. Drug

• Levothyroxine (L-T4) – drug of choice.

  • Dose:

    • Neonates: 10–15 µg/kg/day.

    • Infants: 8–10 µg/kg/day.

    • Children: 4–6 µg/kg/day.

    • Adolescents: 2–4 µg/kg/day.

  • Given on empty stomach (preferably crushed with water or milk).

C. Monitoring

Target: Free T4 in upper half of normal range, TSH normal.

D. Developmental Follow-up

• Neurodevelopmental assessment

• Hearing evaluation

• Growth chart monitoring

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10. Prognosis

• Normal IQ if therapy started within first 2 weeks of life.

• Delay in treatment → irreversible intellectual deficit.

• Acquired forms usually fully reversible with treatment.

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11. Key Differentials

• Pituitary insufficiency

• Hypothyroxinemia of prematurity

• Chronic systemic illness (euthyroid sick syndrome)

• Constitutional growth delay

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12. Summary Table

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References

1. Nelson Textbook of Pediatrics, 22nd ed.

2. Indian Academy of Pediatrics Guidelines (2021) — Screening and management of congenital hypothyroidism.

3. Endocrine Society Clinical Practice Guideline (2020) – Congenital Hypothyroidism.

4. Sperling MA, Pediatric Endocrinology, 5th ed.