Overview

Definition:
-Congenital hypothyroidism (CH) is a condition characterized by inadequate production of thyroid hormone by the infant's thyroid gland from birth
-It is a leading preventable cause of intellectual disability.
Epidemiology:
-The incidence of CH varies globally but is generally reported as 1 in 1500 to 4000 live births
-Transient CH can occur due to maternal factors or medications, but permanent CH is more common.
Clinical Significance:
-Early diagnosis and prompt treatment of CH are crucial to prevent irreversible neurological damage and ensure normal growth and development
-Untreated CH leads to severe developmental delays, impaired cognitive function, and characteristic physical features.

Clinical Presentation

Symptoms:
-Many newborns with CH are asymptomatic at birth
-Symptoms may become apparent within the first few weeks or months of life and can include: Prolonged jaundice
-Poor feeding and weight gain
-Constipation
-Hypotonia and lethargy
-Cool, mottled skin
-Umbilical hernia
-Enlarged fontanelles
-Respiratory distress.
Signs:
-Physical examination may reveal: Bradycardia
-Hypotonia
-Macroglossia (large tongue)
-Coarse facial features
-Dry skin
-Deep tendon reflexes with delayed relaxation
-Shortening of the long bones (visible on X-ray)
-Abdominal distension.
Diagnostic Criteria:
-Diagnosis is primarily based on elevated TSH and low T4 levels in newborn screening tests
-Confirmatory testing includes measurement of serum TSH, free T4 (fT4), and sometimes total T4
-Ultrasound of the thyroid gland and thyroid scintigraphy may be used to assess thyroid anatomy and function, identifying the cause (e.g., dysgenesis, dyshormonogenesis).

Diagnostic Approach

History Taking: Key history points include maternal thyroid status and treatment during pregnancy, family history of thyroid disorders or autoimmune diseases, exposure to iodinated contrast agents or certain medications during gestation, and birth history (prematurity, birth weight, birth asphyxia).
Physical Examination:
-A thorough physical examination focusing on signs of hypothyroidism is essential
-This includes assessing vital signs, general appearance, neurological status (tone, reflexes), facial features, skin condition, abdomen (hernias), and cardiac auscultation.
Investigations:
-Newborn screening typically involves measuring TSH or T4 on a blood spot collected from the heel
-Confirmatory tests include: Serum TSH: Elevated (>10-20 mIU/L depending on assay and cutoff) is the primary indicator of primary hypothyroidism
-Serum Free T4 (fT4): Low (<1.0-1.5 ng/dL or <10-15 pmol/L) confirms primary hypothyroidism
-Serum Total T4: Can be used but is affected by binding protein levels
-Thyroid Ultrasound: To assess gland size, location, and morphology
-Thyroid Scintigraphy with Iodine-123 or Technetium-99m: To evaluate thyroid uptake and identify ectopic or absent thyroid tissue.
Differential Diagnosis:
-Transient hypothyroidism (maternal antibodies, excess iodine exposure, prematurity, sick euthyroid syndrome) must be distinguished from permanent CH
-Central hypothyroidism (pituitary or hypothalamic defects) presents with low TSH and low fT4.

Management

Initial Management:
-Treatment should be initiated as soon as CH is diagnosed, ideally within the first few weeks of life
-The goal is to normalize thyroid hormone levels as quickly as possible to prevent neurodevelopmental deficits.
Medical Management:
-Levothyroxine (L-T4) sodium is the drug of choice for CH
-The initial dose is typically 10-15 mcg/kg/day, administered orally once daily
-The dose should be adjusted based on serial thyroid function tests (TSH and fT4) to maintain TSH within the normal range for age and fT4 in the upper half of the normal range
-Regular monitoring is crucial.
Surgical Management: Surgery is generally not indicated for congenital hypothyroidism itself, unless there are co-existing structural abnormalities of the thyroid gland (e.g., thyroglossal duct cyst requiring excision) or very rarely for managing iodine-refractory congenital goiter in specific circumstances.
Supportive Care:
-Supportive care includes ensuring proper administration of medication, monitoring for side effects, nutritional support, and addressing any associated developmental or growth issues
-Parents require extensive education and support.

Age Specific Dosing

Initial Dosing: Recommended starting dose for permanent CH: 10-15 mcg/kg/day of levothyroxine.
Infants 0 3 Months:
-Target TSH: <10 mIU/L
-Target fT4: Upper half of normal range (e.g., 1.2-1.7 ng/dL or 15-22 pmol/L)
-Dose adjustments based on TSH and fT4 levels.
Infants 3 12 Months:
-Target TSH: <5 mIU/L
-Target fT4: Upper half of normal range
-Dose adjustments as needed, considering growth.
Children 1 To 12 Years:
-Target TSH: 0.5-5 mIU/L
-Target fT4: Upper half of normal range
-Dose adjustments based on growth and puberty.
Adolescents:
-Target TSH: 0.5-5 mIU/L
-Target fT4: Upper half of normal range
-Dosing may need adjustment during puberty due to increased thyroid hormone requirements.

Monitoring And Follow Up

Initial Monitoring:
-Within 1-2 weeks of starting therapy, check TSH and fT4
-Adjust levothyroxine dose to achieve target levels within 1 month.
Routine Monitoring:
-In the first year of life, monitor TSH and fT4 every 1-3 months
-Subsequently, monitor every 3-6 months until 3 years of age, then annually
-During puberty, monitoring every 6 months may be necessary.
Long Term Follow Up:
-Lifelong monitoring of thyroid function is required
-Assess growth, neurodevelopmental status, and bone age periodically
-Monitor for potential complications and adherence to medication.

Complications

Early Complications:
-If treatment is delayed or inadequate: Severe cognitive impairment and developmental delay
-Poor growth
-Constipation
-Jaundice
-Cardiac dysfunction (e.g., bradycardia).
Late Complications:
-Long-term consequences of inadequately treated CH can include: Persistent developmental delays
-Learning disabilities
-Short stature
-Pubertal delays
-Potential effects on cardiovascular health and metabolic function.
Prevention Strategies:
-Early and accurate newborn screening is paramount
-Prompt initiation of appropriate levothyroxine therapy and meticulous monitoring to achieve and maintain biochemical euthyroidism are key to preventing complications.

Key Points

Exam Focus:
-Importance of newborn screening for CH
-Typical initial levothyroxine dose (10-15 mcg/kg/day)
-Target TSH and fT4 levels for different age groups
-Causes of permanent CH (dysgenesis vs
-dyshormonogenesis)
-Long-term monitoring requirements.
Clinical Pearls:
-Always consider maternal thyroid status in pregnant women
-Levothyroxine is best absorbed on an empty stomach, ideally 30-60 minutes before feeding
-Pill crushing and mixing with water or breast milk is acceptable
-avoid mixing with soy formula or iron supplements, which can interfere with absorption.
Common Mistakes:
-Delaying treatment initiation or dose adjustment
-Using incorrect target values for TSH/fT4
-Inadequate monitoring leading to undertreatment or overtreatment
-Poor patient/parent education regarding medication adherence and administration.