Overview/Definition
Definition:
• Congenital hypothyroidism (CH) is deficiency of thyroid hormone from birth due to thyroid dysgenesis (80-85%), dyshormonogenesis (10-15%), or central hypothyroidism (5%)
Most common preventable cause of intellectual disability with excellent prognosis if diagnosed and treated early within first 2-4 weeks of life.
Epidemiology:
• Global incidence 1:2000-4000 newborns with higher rates in certain populations
In India, estimated incidence 1:2500-3500 newborns based on limited screening data
Female to male ratio 2:1
Higher incidence in Down syndrome, preterm infants
Iodine deficiency affects regional prevalence patterns.
Age Distribution:
• Neonatal period: Critical window for diagnosis (0-28 days) to prevent irreversible brain damage
Infancy (1-24 months): Continued high sensitivity to thyroid hormone deficiency for brain development
Childhood (2-12 years): Growth and developmental impacts
Adolescence: Pubertal development and final height achievement.
Clinical Significance:
• High-yield topic for DNB Pediatrics and NEET SS examinations focusing on screening protocols, diagnostic criteria, treatment initiation, and long-term monitoring
Understanding newborn screening programs, false positive/negative rates, and emergency management essential
Critical for preventing intellectual disability.
Age-Specific Considerations
Newborn:
• Neonates (0-28 days): Newborn screening typically performed 48-72 hours after birth when TSH surge occurs
Preterm infants may need repeat screening due to immature hypothalamic-pituitary-thyroid axis
Screen before blood transfusion or discharge
Emergency treatment for severe hypothyroidism with bradycardia, hypothermia.
Infant:
• Infants (1-24 months): Most critical period for treatment to prevent intellectual disability
Rapid brain growth requires adequate thyroid hormone
Monitor growth velocity, developmental milestones closely
Adjust dosing frequently based on growth
Higher per-weight levothyroxine requirements compared to older children.
Child:
• Children (2-12 years): Continue treatment with regular monitoring
Growth rate excellent indicator of adequacy
School performance and cognitive development assessment important
Dosing adjustments less frequent but still weight-based
Transition from liquid to tablet formulations possible.
Adolescent:
• Adolescents (12-18 years): Pubertal development requires adequate thyroid hormone
Final height achievement depends on treatment adequacy
Medication compliance issues common
Adult-like dosing approaches
Transition planning to adult endocrinology care.
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Clinical Presentation
Symptoms:
• Early neonatal symptoms often subtle: Prolonged jaundice >2 weeks, feeding difficulties, lethargy, constipation
Later symptoms if untreated: Developmental delays, growth retardation, intellectual disability
Older children: Fatigue, cold intolerance, weight gain, school performance decline
Pubertal delays in adolescents.
Physical Signs:
• Neonatal signs: Macroglossia, umbilical hernia, hypotonia, mottled skin
Growth parameters: Length/height below percentiles, delayed weight gain
Facial features: Puffy face, thick lips, enlarged fontanelles
Cardiovascular: Bradycardia, murmurs
Developmental: Delayed milestones, hyporeflexia.
Severity Assessment:
• Mild CH: TSH 20-50 mIU/L, minimal symptoms, normal T4
Moderate CH: TSH 50-100 mIU/L, some symptoms, low-normal T4
Severe CH: TSH >100 mIU/L, significant symptoms, low T4
Central CH: Low/normal TSH with low T4, often part of multiple pituitary hormone deficiency.
Differential Diagnosis:
• Transient hypothyroidism: Maternal antithyroid drugs, iodine excess/deficiency, prematurity
Other causes of developmental delay: Genetic syndromes, metabolic disorders
Growth failure: Growth hormone deficiency, malnutrition, chronic illness
Neonatal jaundice: Biliary atresia, sepsis, hemolysis.
Diagnostic Approach
History Taking:
• Family history: Thyroid disorders, autoimmune diseases, consanguinity
Maternal history: Thyroid disease, medications (antithyroid drugs, iodine), radiation exposure
Neonatal history: Birth weight, gestational age, jaundice, feeding problems
Developmental history: Milestone achievements, growth patterns.
Investigations:
• Newborn screening: TSH measurement from dried blood spot (Guthrie card)
Confirmatory tests: Serum TSH, free T4, total T4
Additional tests: Thyroglobulin, thyroid peroxidase antibodies, thyroid ultrasound
Imaging: Thyroid scintigraphy to differentiate agenesis, dysgenesis, ectopia.
Normal Values:
• Newborn TSH: <20 mIU/L (screening), <10 mIU/L (serum)
Free T4: 10-25 pmol/L (0.8-2.0 ng/dL)
Total T4: 65-175 nmol/L (5-13.5 μg/dL)
Target ranges on treatment: TSH 0.5-2.0 mIU/L (first year), 0.5-4.0 mIU/L (after 1 year)
Free T4 upper half of normal range.
Interpretation:
• Screening positive: TSH >20 mIU/L requires immediate confirmatory testing
Confirmatory: TSH >10 mIU/L with low/low-normal T4 confirms diagnosis
Transient forms: Normalize by 3-6 months, may require temporary treatment
Central CH: Low T4 with inappropriately low/normal TSH.
Management/Treatment
Acute Management:
• Emergency situations: Severe hypothyroidism with cardiovascular compromise requires immediate IV levothyroxine
Newborn diagnosis: Start treatment immediately, do not wait for confirmatory results if high clinical suspicion
Initial dosing: 10-15 μg/kg/day levothyroxine orally.
Chronic Management:
• Long-term levothyroxine replacement therapy for life
Regular monitoring: TSH, free T4 every 2-4 weeks initially, then every 2-3 months first year, every 3-4 months thereafter
Dose adjustments: Based on TSH, free T4, growth velocity, development
Brand consistency important.
Lifestyle Modifications:
• Medication timing: Give on empty stomach, 30-60 minutes before feeding
Avoid simultaneous administration with iron, calcium, soy formula
Regular meal timing to optimize absorption
Normal physical activity encouraged
Adequate iodine intake in diet.
Follow Up:
• Intensive monitoring first year: Every 2-4 weeks initially, then every 2-3 months
Childhood monitoring: Every 3-4 months with growth and development assessment
Adolescence: Every 4-6 months with pubertal assessment
Adult transition: Gradual transfer to adult endocrinology.
Age-Specific Dosing
Medications:
• Levothyroxine starting doses: Neonates (0-3 months): 10-15 μg/kg/day
Infants (3-6 months): 8-10 μg/kg/day
Children (6 months-2 years): 6-8 μg/kg/day
Children (2-12 years): 4-6 μg/kg/day
Adolescents (12-18 years): 2-4 μg/kg/day, transitioning to adult dosing.
Formulations:
• Available strengths: 25, 50, 75, 88, 100, 112, 125, 137, 150, 175, 200 μg tablets
Liquid formulation available for infants and children with swallowing difficulties
Crushing tablets: Can be crushed and mixed with small amount of water, breast milk, or formula (not soy-based).
Safety Considerations:
• Drug interactions: Iron supplements, calcium, soy products reduce absorption (separate by 4 hours)
Overtreatment risks: Tachycardia, irritability, sleep disturbances, accelerated bone maturation
Undertreatment: Growth failure, developmental delays, intellectual disability.
Monitoring:
• Growth parameters: Weight, length/height, head circumference plotted on growth charts
Developmental assessment: Milestone achievements, cognitive testing
Laboratory monitoring: TSH, free T4 levels
Cardiac assessment: Heart rate, blood pressure
Bone age assessment if growth concerns.
Prevention & Follow-up
Prevention Strategies:
• Primary prevention: Adequate maternal iodine intake during pregnancy
Universal newborn screening programs for early detection
Public health measures: Iodized salt programs, population iodine supplementation
Genetic counseling for families with hereditary forms.
Vaccination Considerations:
• No specific vaccine modifications required
Follow routine immunization schedule
Thyroid hormone replacement does not affect vaccine efficacy or safety
Live vaccines can be given normally
Monitor for intercurrent illnesses affecting thyroid hormone requirements.
Follow Up Schedule:
• First year: Every 2-4 weeks until stable, then every 2-3 months
Childhood: Every 3-4 months with interim visits for dose adjustments
Adolescence: Every 4-6 months
Sick visits: During illnesses that may affect absorption or metabolism
Pre-conception counseling for females.
Monitoring Parameters:
• Laboratory: TSH, free T4 levels targeting normal ranges
Growth: Linear growth velocity, weight gain patterns
Development: Milestone achievements, IQ testing at school age
Compliance: Medication adherence assessment
Quality of life: School performance, social functioning.
Complications
Acute Complications:
• Overtreatment: Hyperthyroidism symptoms (tachycardia, irritability, sleep disturbances), accelerated bone maturation, craniosynostosis in infants
Undertreatment: Developmental delays, intellectual disability, growth failure
Medication errors: Wrong dosing, formulation issues.
Chronic Complications:
• Intellectual disability: If treatment delayed beyond 2-4 weeks or inadequately treated
Growth failure: Final height compromise with late or inadequate treatment
Learning difficulties: Subtle cognitive deficits even with early treatment
Behavioral problems: ADHD-like symptoms, social difficulties.
Warning Signs:
• Signs of overtreatment: Rapid heart rate, irritability, excessive activity, sleep problems
Signs of undertreatment: Lethargy, poor growth, developmental delays, persistent symptoms
Medication absorption issues: Vomiting, diarrhea, drug interactions.
Emergency Referral:
• Immediate pediatric endocrinology referral for: Diagnostic uncertainty, treatment resistance, severe hypothyroidism
Cardiology referral for cardiac complications
Developmental assessment for delays
Genetics referral for familial forms or associated syndromes.
Parent Education Points
Counseling Points:
• Congenital hypothyroidism is treatable condition with excellent prognosis if treated early and adequately
Lifelong medication required but allows normal development
Importance of medication compliance and regular monitoring
Early treatment prevents intellectual disability.
Home Care:
• Medication administration: Give on empty stomach, same time daily, avoid mixing with soy, iron, calcium
Store medication in cool, dry place
Monitor for signs of over/under treatment
Maintain medication supply, refill prescriptions timely
Keep medication diary.
Medication Administration:
• Levothyroxine timing: 30-60 minutes before first feeding
Crushing tablets: Mix with small amount of water, give immediately
Avoid grapefruit juice, high-fiber foods near medication time
Consistency in timing and administration method important for stable levels.
When To Seek Help:
• Contact healthcare provider for: Signs of overtreatment (rapid heartbeat, irritability), undertreatment (lethargy, poor growth), missed doses for several days
Illness affecting medication absorption
Concerns about growth or development
Medication supply issues or side effects.