What is the recommended treatment for congenital hypothyroidism?

Congenital Hypothyroidism Treatment Guidelines

Immediate Treatment Initiation

Levothyroxine therapy must be started immediately upon diagnosis confirmation, without waiting for imaging studies, to prevent irreversible neurocognitive damage. 1, 2

• Treatment should begin as soon as elevated TSH and low thyroid hormone levels confirm the diagnosis 1
• Diagnostic imaging (ultrasonography, scintigraphy, thyroglobulin measurement) should not delay treatment initiation 1
• Therapy commenced within the first 2 weeks of life prevents mental retardation in >90% of children with congenital hypothyroidism 1

Initial Levothyroxine Dosing

The recommended starting dose is 10-15 mcg/kg/day of levothyroxine, administered orally once daily. 2

Dose Selection Based on Severity

• For infants with TSH >100 μIU/L at diagnosis: start with 10-11.9 mcg/kg/day 3
• For infants with TSH <100 μIU/L at diagnosis: start with 8-10 mcg/kg/day 3
• Doses of 10-14 mcg/kg/day safely restore clinical and biochemical euthyroidism within the first week 4

Critical Dosing Considerations

• Starting doses >12 mcg/kg/day frequently cause overtreatment at 1 month follow-up 3
• In one study, 75% of infants receiving 12-15 mcg/kg/day were overtreated at 1 month 3
• Lower doses (10-11.9 mcg/kg/day) achieved target thyroid levels in 55% of patients, with 30% overtreated and 15% undertreated 3

Treatment Goals and Monitoring

Maintain TSH in the normal range with free T4 in the upper half of the age-specific reference range during the first 3 years of life. 2

Biochemical Response Timeline

• Serum total T4 and free T4 normalize within 1 week of starting therapy in all patients 4
• TSH suppression occurs more rapidly in infants with dyshormonogenesis compared to thyroid dysgenesis 4

Monitoring Schedule

• Monitor infants closely during the first 2 weeks of therapy for cardiac overload and arrhythmias 5
• Measure serum TSH and free T4 at regular intervals to guide dose adjustments 2
• Overtreatment is defined as T4 >16 μg/dL or free T4 >2.3 ng/dL with TSH <0.5 μIU/L 3
• Undertreatment is defined as TSH >6 μIU/L at 1 month 3

Long-Term Dose Requirements

Levothyroxine requirements progressively decrease during childhood, regardless of etiology. 6

Age-Specific Dosing

• Pre-school children (ages 1-5 years): 3-4 mcg/kg/day (70-90 mcg/m²/day) 6
• School-age children (ages 6-12 years): 2-3 mcg/kg/day (60-80 mcg/m²/day) 6
• The dose required at 6 months of age predicts requirements until 12 years of age 6

Etiology-Based Differences

• Infants with in situ thyroid glands require significantly lower doses than those with athyreosis throughout childhood 6
• Infants with in situ glands require less frequent dose adjustments (36%) compared to ectopic glands (41.4%) or athyreosis (43.6%) 6

Special Populations

Pregnancy and Maternal Hypothyroidism

• Untreated maternal hypothyroidism causes spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, and premature delivery 7, 5
• Maternal hypothyroidism adversely affects fetal neurocognitive development 7, 5
• Levothyroxine should never be discontinued during pregnancy 5
• TSH levels increase during pregnancy, requiring dose adjustments 5
• Postpartum levothyroxine dose should return to pre-pregnancy levels immediately after delivery 5

Neonatal Screening Limitations

• Clinical symptoms of hypothyroidism (large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, hypothermia) warrant thyroid function testing regardless of normal newborn screening results 2
• Newborn screening alone is insufficient to prevent all adverse outcomes from congenital hypothyroidism 2
• 70% of neonates worldwide do not undergo newborn screening 2

Critical Safety Considerations

Cardiac Monitoring

• Elderly patients and those with cardiovascular disease require lower starting doses due to increased risk of cardiac complications 5
• Atrial fibrillation is the most common arrhythmia with levothyroxine overtreatment in elderly patients 5
• Rapid restoration of thyroid hormone levels in infants requires close cardiac monitoring during the first 2 weeks 5

Adrenal Insufficiency

• In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, corticosteroids must be started before levothyroxine to prevent adrenal crisis 8

Overtreatment Risks

• Levothyroxine overtreatment increases risk for osteoporosis, fractures, atrial fibrillation, and cardiac complications 8
• Approximately 25% of patients are inadvertently maintained on excessive doses that fully suppress TSH 8

Lifelong Treatment

Levothyroxine therapy is generally continued for life in patients with permanent congenital hypothyroidism. 5

• Treatment ensures normal growth and neuropsychological development throughout childhood 6
• Consistent euthyroidism during the first 3 years of life is critical for optimal neurocognitive outcomes 2