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:
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Congenital (Neonatal) – present at birth.
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Acquired (Childhood) – develops later due to autoimmune, iatrogenic, or other causes.
2. Classification
A. Based on Level of Defect
| Type | Site of Defect | TSH | T4/T3 |
|---|---|---|---|
| Primary | Thyroid gland | ↑ | ↓ |
| Secondary | Pituitary | ↓/N | ↓ |
| Tertiary | Hypothalamus | ↓/N | ↓ |
| Peripheral (Resistance) | Target tissue | N/↑ | N/↑ |
B. Based on Onset
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Congenital hypothyroidism (CH)
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Acquired hypothyroidism
3. Epidemiology
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CH: ~1 in 2,000–4,000 live births.
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More common in females.
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Acquired form common in older children/adolescents, often autoimmune (Hashimoto’s).
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| thyroid gland |
4. Etiology
A. Congenital Hypothyroidism
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Thyroid dysgenesis (80–85%)
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Agenesis, ectopy, or hypoplasia.
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Usually sporadic.
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Dyshormonogenesis (10–15%)
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Inborn errors of thyroid hormone synthesis (autosomal recessive).
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E.g. TPO, TG, Pendrin, NIS mutations.
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Central hypothyroidism (rare)
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Pituitary/hypothalamic malformation, midline defects.
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Transient CH
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Iodine excess/deficiency, maternal antibodies or antithyroid drugs.
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Thyroid hormone resistance – extremely rare.
B. Acquired Hypothyroidism
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Autoimmune thyroiditis (Hashimoto’s) – most common.
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Iodine deficiency/excess.
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Post-irradiation or post-surgical.
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Drugs: amiodarone, lithium, interferon-α.
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Secondary causes: pituitary tumors, craniopharyngioma.
5. Pathophysiology
↓ Thyroid hormone → ↓ metabolic activity → impaired CNS myelination, growth retardation, delayed bone maturation.
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In neonates: irreversible neurodevelopmental impairment if untreated.
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In older children: growth failure and delayed puberty predominate.
6. Clinical Features
A. Neonatal / Congenital
Often asymptomatic at birth due to transplacental maternal T4.
Typical features (develop over weeks):
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Prolonged jaundice
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Lethargy, hypotonia
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Feeding difficulty, constipation
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Large fontanelles
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Macroglossia
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Umbilical hernia
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Cold, dry skin
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Hoarse cry
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Poor growth
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Delayed bone age
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Delayed milestones (later)
B. Childhood / Acquired
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Growth retardation, short stature
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Weight gain with poor height velocity
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Fatigue, cold intolerance
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Constipation
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Dry skin, coarse hair
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Bradycardia
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Delayed puberty / menstrual irregularities
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Pseudoprecocious puberty (rare, due to high TRH → prolactin ↑)
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Goiter (especially in Hashimoto’s)
7. Investigations
A. Screening
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Neonatal screening: heel-prick sample at 48–72 hr.
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Primary TSH (most programs).
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Elevated TSH → confirm with serum free T4.
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B. Diagnostic Tests
| Test | Interpretation |
|---|---|
| Serum TSH, Free T4 | ↓T4 with ↑TSH → primary hypothyroidism |
| T3 | less reliable in neonates |
| Thyroglobulin | Low in agenesis, high in dyshormonogenesis |
| Imaging | Thyroid scan (99mTc or I-123) – ectopy, agenesis, uptake defects |
| Ultrasound | Gland location and size |
| Antibodies (TPO, Tg) | Positive in autoimmune |
| Bone age X-ray | Delayed |
| Additional: Pituitary MRI if central hypothyroidism suspected |
8. Complications (if untreated)
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Neurologic: irreversible intellectual disability, deaf-mutism, spasticity.
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Growth: severe stunting, delayed bone age.
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Metabolic: dyslipidemia.
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Cardiac: bradycardia, pericardial effusion.
9. Management
A. Principles
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Early, adequate, lifelong replacement.
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Monitor and titrate carefully to maintain euthyroid state.
B. Drug
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Levothyroxine (L-T4) – drug of choice.
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Dose:
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Neonates: 10–15 µg/kg/day.
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Infants: 8–10 µg/kg/day.
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Children: 4–6 µg/kg/day.
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Adolescents: 2–4 µg/kg/day.
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Given on empty stomach (preferably crushed with water or milk).
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C. Monitoring
| Age | Frequency | Parameters |
|---|---|---|
| 0–6 mo | Every 2 wk till T4 normal, then q1–2 mo | T4, TSH |
| 6–12 mo | q2–3 mo | 〃 |
| 1–3 yr | q3–4 mo | 〃 |
| >3 yr | q6–12 mo | 〃 |
Target: Free T4 in upper half of normal range, TSH normal.
D. Developmental Follow-up
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Neurodevelopmental assessment
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Hearing evaluation
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Growth chart monitoring
10. Prognosis
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Normal IQ if therapy started within first 2 weeks of life.
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Delay in treatment → irreversible intellectual deficit.
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Acquired forms usually fully reversible with treatment.
11. Key Differentials
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Pituitary insufficiency
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Hypothyroxinemia of prematurity
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Chronic systemic illness (euthyroid sick syndrome)
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Constitutional growth delay
12. Summary Table
| Feature | Congenital | Acquired |
|---|---|---|
| Onset | Birth | Childhood/adolescence |
| Cause | Dysgenesis > dyshormonogenesis | Hashimoto’s most common |
| Presentation | Lethargy, constipation, macroglossia | Growth failure, delayed puberty |
| TSH | High | High |
| T4 | Low | Low |
| Rx | Levothyroxine | Levothyroxine |
| Prognosis | Excellent if early | Excellent |
References
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Nelson Textbook of Pediatrics, 22nd ed.
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Indian Academy of Pediatrics Guidelines (2021) — Screening and management of congenital hypothyroidism.
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Endocrine Society Clinical Practice Guideline (2020) – Congenital Hypothyroidism.
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Sperling MA, Pediatric Endocrinology, 5th ed.