• Treatment adequacy is monitored by measuring serum free thyroxine (FT₄) & thyroid-stimulating hormone (TSH) levels
• T₄ dose adjusted by 25-50 mcg increments based on the serum TSH level measured 2-4 weeks after starting treatment & every 4-6 weeks thereafter until normal TSH is reached
  
  • In children, serum TSH & FT₄ levels should be assessed based on age-specific & method-specific reference ranges
• Once a target level of serum TSH is reached, measure TSH & FT₄ levels every 2-3 months, provided that no other medications are taken that may change the bioavailability or absorption of the T₄
  
  • When patient has to switch to a different T₄ brand, serum TSH must be checked 2-4 weeks later, then doses adjusted accordingly
  • Intake of other medications that may alter T₄ bioavailability warrants rechecking of serum TSH after 4-6 weeks & adjusting of T₄ doses if needed

Considerations

Central hypothyroidism

• TSH is not used as a marker of adequate treatment
• Serum FT₄ is a useful index

Congenital hypothyroidism

• Infants are monitored frequently in the first 2 years of life using serum TSH as primary parameter & FT₄ as the secondary parameter, employing age-appropriate reference intervals
• During the 1st year of life, total T₄ & FT₄ is maintained in the upper half of the normal reference range
• Monitoring:
  
  • Recheck T₄, TSH
  • 2-4 weeks after initial treatment has begun
  • Every 1-2 months in first 6 months of life
  • Every 3-4 months between 6 months-3 years of age
  • Every 6-12 months from 3 years of age until end of growth
  • For patients suspected of treatment noncompliance or w/ abnormal lab results, monitor more frequently
  • Obtain FT₄ & TSH measurements 4-6 weeks after T₄ dose adjustments
  • Blood samples for FT₄ & TSH measurements should be collected ≥4 hours after T₄ intake
• Several studies have suggested monthly monitoring for patients w/ the following:
  • Dose adjustment w/in 1 month from prior visit
  • Total T₄/FT₄ measurements w/in the lower half w/in 1 month from prior visit
  • TSH of 5-10 mU/ml & total T₄/FT₄ measurements w/in the lower half w/in 1 month from prior visit
  • TSH >10 mU/ml w/in 1 month from prior visit, even if total T₄/FT₄ levels are in the upper limit of normal
  • TSH <0.1 mU/ml
• Assess permanence of congenital hypothyroidism
  
  • If initial thyroid scan shows ectopic/absent gland, congenital hypothyroidism is permanent
  • If initial TSH is <50 mIU/L & no increase in TSH after newborn period, then trial off therapy at 3 years of age
  • If TSH increases off therapy, consider permanent congenital hypothyroidism
  • Should be performed in children >3 years
• If circulating T₄ levels remain persistently low & TSH remains high despite progressively larger replacement doses of T₄, it is important to determine the possibility of poor compliance
  
  • The most frequent reason for failure to respond to replacement therapy has been interference w/ adsorption by soy-based formulas or w/ medications that contain iron

Thyroid Re-evaluation

• Thyroid axis re-evaluation should be done 4-6 weeks after temporary withdrawal of treatment in patients ≥ 3 years of age
• May be performed in patients <3 years w/ occassional increased TSH levels (eg positive TSH receptor antibodies, eutopic thyroid gland seen on imaging)
• Indicated for the following:
  
  • If not done during infancy
  • Child was born preterm or ill during initial evaluation & treatment
  • Patients w/o known enzyme defects
  • Normal goiter w/ or w/o goiter at initial evaluation
  • Neonates w/ positive thyroid antibodies
  • Patients w/o dosage increase/adjustments since start of treatment
• Should be deferred for those:
  • W/ diagnosed thyroid ectopy, apparent athyreosis, or true athyreosis via imaging
  • Diagnosed w/ dyshormonogenesis via genetic testing