What is congenital hypothyroidism?

Congenital Hypothyroidism

Congenital hypothyroidism is a thyroid hormone deficiency present at birth that requires immediate treatment with levothyroxine to prevent permanent cognitive impairment and growth failure.

Definition and Epidemiology

• Occurs in approximately 1:2,000 to 1:4,000 newborns 1
• More common in females (2:1 female to male ratio) 2
• 85% of cases are sporadic, while 15% are hereditary 2

Etiology

Congenital hypothyroidism can be classified into several categories:

1. Thyroid Dysgenesis (85% of permanent cases) 1

   • Ectopic thyroid gland
   • Thyroid aplasia (complete absence)
   • Thyroid hypoplasia (underdeveloped)
   • Some cases linked to mutations in transcription factors PAX-8 and TTF-2 2

2. Dyshormonogenesis (10-15% of cases) 1

   • Inborn errors of thyroid hormone synthesis
   • Mutations in genes for sodium/iodide symporter, thyroid peroxidase, or thyroglobulin 2

3. Central/Secondary Hypothyroidism

   • Due to pituitary or hypothalamic dysfunction
   • Often part of congenital hypopituitarism 1

4. Transient Congenital Hypothyroidism

   • Common in preterm infants in iodine-deficient areas 1
   • Maternal thyrotropin receptor blocking antibodies (TRB-Ab) 2
   • Maternal medication exposure

Clinical Presentation

Clinical manifestations are often subtle or absent at birth due to:

• Transplacental passage of maternal thyroid hormone
• Residual thyroid function in some infants 1

Common signs and symptoms include:

• Decreased activity and increased sleep
• Feeding difficulties
• Constipation
• Prolonged jaundice
• Myxedematous facies (puffy face)
• Large fontanels
• Macroglossia (large tongue)
• Distended abdomen with umbilical hernia
• Hypotonia (decreased muscle tone) 1

Diagnosis

Newborn Screening

• Most cases are detected through mandatory newborn screening programs
• Methods include primary T4 with backup TSH or primary TSH test 2
• Positive screening results must be confirmed with serum thyroid function tests 1

Confirmatory Testing

• Elevated serum TSH and low T4 or free T4 levels 1
• Additional diagnostic tests to determine etiology:
  • Thyroid radionuclide uptake and scan (most accurate for detecting dysgenesis)
  • Thyroid ultrasound
  • Serum thyroglobulin determination 1

Treatment

Initial Management

• Levothyroxine is the treatment of choice with a recommended starting dose of 10-15 mcg/kg/day 1, 3
• Treatment should begin as soon as possible after confirmation of diagnosis, ideally within the first two weeks of life 1
• Goals of initial treatment:
  • Rapidly raise serum T4 above 130 nmol/L (10 μg/dL)
  • Normalize serum TSH levels 1

Monitoring

• Frequent laboratory monitoring is essential for optimal neurocognitive outcomes
• Check serum TSH and free T4 every 1-2 months in first 6 months of life
• Monitor every 3-4 months thereafter 1
• Adjust levothyroxine dose to maintain:
  • Free T4 in the upper half of the normal range
  • Normal TSH levels 1, 3

Administration Guidelines

• Levothyroxine should be taken as a single daily dose
• Administer on an empty stomach, 30-60 minutes before breakfast
• Take with a full glass of water
• Avoid medications that interfere with absorption 4

Prognosis and Outcomes

• Prognosis is excellent when detected by screening and treated early
• IQ scores similar to siblings or classmate controls when treatment is optimal 1
• Poorer neurocognitive outcomes may occur with:
  • Later treatment initiation (>30 days of age)
  • Lower levothyroxine doses than currently recommended
  • More severe hypothyroidism at diagnosis 1

Special Considerations

Pregnancy

• Maternal hypothyroidism during pregnancy is associated with:
  • Higher rates of spontaneous abortion
  • Gestational hypertension
  • Preeclampsia
  • Stillbirth
  • Premature delivery
  • Adverse effects on fetal neurocognitive development 3
• TSH levels should be monitored and levothyroxine dosage adjusted during pregnancy 3

Elderly Patients

• Start with lower doses of levothyroxine (25-50 mcg/day) for elderly patients
• Titrate slowly to avoid cardiac complications 4
• Monitor for atrial arrhythmias, which are more common in elderly patients with overtreatment 3

Complications of Untreated or Undertreated Congenital Hypothyroidism

• Permanent cognitive impairment
• Growth failure
• Delayed development
• In severe cases, cretinism (growth failure, mental retardation, and other neuropsychologic defects) 5

Complications of Overtreatment

• Subclinical hyperthyroidism
• Increased risk of atrial fibrillation
• Decreased bone mineral density and increased fracture risk in postmenopausal women 4

Early diagnosis and proper treatment of congenital hypothyroidism are critical to prevent permanent neurological damage and ensure normal growth and development.