Overview
Definition:
Congenital hypothyroidism (CH) is a condition characterized by inadequate production of thyroid hormones by the thyroid gland in infants from birth
It is a leading cause of preventable intellectual disability.
Epidemiology:
The incidence of CH varies by screening method and population, typically ranging from 1 in 2,000 to 1 in 4,000 live births
Permanent CH accounts for the majority of cases, with transient forms being less common.
Clinical Significance:
Early diagnosis and prompt treatment of CH are crucial to prevent irreversible neurodevelopmental deficits and ensure normal physical and cognitive growth
Untreated CH can lead to severe intellectual disability, growth failure, and characteristic dysmorphic features.
Diagnostic Approach
History Taking:
A detailed family history for thyroid disease or autoimmune disorders is important
Maternal history of iodine deficiency or exposure to antithyroid medications during pregnancy is relevant
In infants not screened, history of prolonged jaundice, poor feeding, constipation, hypothermia, lethargy, and respiratory distress may be present.
Physical Examination:
Key findings may include prolonged jaundice, hypothermia, poor sucking/feeding, lethargy, hypotonia, a large fontanelle, umbilical hernia, hoarse cry, dry skin, constipation, and characteristic facial features (e.g., puffy face, flattened nasal bridge).
Investigations:
Confirmatory testing involves measuring serum TSH and free T4
Elevated TSH (>10-20 mIU/L, depending on lab reference range and age) with low free T4 (<1.0-1.5 ng/dL or <13-20 nmol/L) confirms diagnosis
Repeat testing is essential to rule out transient elevations or laboratory errors
Thyroid imaging (ultrasound or radionuclide scan) may be used to determine the cause (e.g., thyroid dysgenesis vs
dyshormonogenesis) and location of the thyroid gland.
Differential Diagnosis:
Differential diagnosis for elevated TSH and low T4 includes primary hypothyroidism (most common), secondary hypothyroidism (pituitary or hypothalamic dysfunction), transient hypothyroidism due to maternal factors, and laboratory inaccuracies.
Management
Initial Management:
Treatment should be initiated as soon as diagnosis is confirmed, ideally within the first few weeks of life
The goal is to normalize thyroid hormone levels and promote normal growth and development.
Medical Management:
Levothyroxine (L-T4) is the medication of choice
The initial dose is typically 10-15 mcg/kg/day orally.
Age Specific Dosing:
Initial dosing for CH is usually 10-15 mcg/kg/day
Dosing is adjusted based on TSH and free T4 levels, aiming for TSH <5 mIU/L and free T4 in the upper half of the normal range for age
Infants on L-T4 require frequent monitoring and dose adjustments, especially during the first 2-3 years of life as their weight and metabolic needs change.
Monitoring:
Regular follow-up is essential
Thyroid function tests (TSH and free T4) should be checked at 2 weeks, 4 weeks, 8 weeks, and then every 3-6 months until 3 years of age, and then annually
Monitoring of growth (height and weight) and neurodevelopment is also crucial.
Complications
Early Complications:
If untreated or inadequately treated, infants can develop symptoms of severe hypothyroidism, including failure to thrive, respiratory distress, feeding difficulties, and neurological impairment.
Late Complications:
Long-term complications of untreated CH include severe intellectual disability, growth retardation, delayed puberty, and impaired hearing and vision
Even with treatment, subtle neurodevelopmental deficits can occur if treatment initiation or titration is delayed.
Prevention Strategies:
Universal newborn screening programs are the cornerstone of preventing severe outcomes
Prompt confirmatory testing and initiation of L-T4 therapy are critical
Adherence to medication and regular follow-up with endocrinology services are vital for optimal outcomes.
Key Points
Exam Focus:
Understand the screening process vs
confirmatory testing
Know the typical initial dose of levothyroxine and the target laboratory values for monitoring
Recognize the importance of early diagnosis for preventing intellectual disability.
Clinical Pearls:
Always recheck thyroid function tests if initial results are abnormal, especially in the context of a critical illness or sample collection issues
Ensure adequate absorption of levothyroxine by advising parents to administer it on an empty stomach
Counsel parents on the lifelong nature of treatment for permanent CH.
Common Mistakes:
Delaying confirmatory testing or treatment
Incorrect initial dosing or inadequate dose adjustments based on follow-up tests
Over-reliance on screening values without confirmatory testing
Incorrect interpretation of thyroid function tests in sick neonates.