What is the proper dosing for levothyroxine (T4) therapy?

Levothyroxine Dosing Guidelines

The recommended starting dose of levothyroxine for hypothyroidism in adults is 1.6 mcg/kg/day, with dose titration by 12.5-25 mcg increments every 4-6 weeks until the patient is euthyroid and TSH normalizes. 1, 2

Initial Dosing Strategy

• For adults without cardiac disease or significant comorbidities, start with the full replacement dose of 1.6 mcg/kg/day 1, 2
• For patients >70 years or with cardiac disease/multiple comorbidities, start with a lower dose of 25-50 mcg/day 1, 2
• For patients at risk of atrial fibrillation or with underlying cardiac disease, use a lower starting dose (less than 1.6 mcg/kg/day) and titrate more slowly to avoid exacerbation of cardiac symptoms 2
• For pediatric patients, dosing is age-dependent, ranging from 10-15 mcg/kg/day for infants 0-3 months to 1.6 mcg/kg/day for adolescents with complete growth and puberty 2

Dose Titration and Monitoring

• Titrate dosage by 12.5-25 mcg increments every 4-6 weeks until the patient is euthyroid 1, 3, 2
• For elderly patients or those with cardiac disease, use smaller increments (12.5 mcg) and titrate every 6-8 weeks 1, 2
• Monitor TSH every 6-8 weeks while titrating hormone replacement 1
• Once adequately treated, repeat testing every 6-12 months or if symptoms change 1
• The peak therapeutic effect of a given dose may not be attained for 4-6 weeks 2

Special Populations

Pregnancy

• For pregnant patients with pre-existing hypothyroidism, measure TSH and free T4 as soon as pregnancy is confirmed and during each trimester 2
• Increase levothyroxine dosage by 12.5-25 mcg per day if TSH is above the normal trimester-specific range 2
• Women who become pregnant should increase their weekly dosage by 30% (take one extra dose twice per week) 4

Secondary or Tertiary Hypothyroidism

• Do not use serum TSH to monitor therapy 2
• Use serum free-T4 levels to titrate dosing until the patient is clinically euthyroid and free-T4 is restored to the upper half of the normal range 2

TSH Suppression for Thyroid Cancer

• Dosing is based on the target level of TSH suppression for the stage and clinical status of thyroid cancer 2
• Target TSH levels may be intentionally suppressed (0.1-0.5 mIU/ml) for patients with biochemical incomplete or indeterminate responses to treatment 1

Administration Guidelines

• Administer levothyroxine at least 4 hours before or after drugs known to interfere with absorption 2
• Take on an empty stomach, at least 30 minutes before breakfast 5
• For pediatric patients who cannot swallow tablets, crush the tablet and suspend in a small amount of water for immediate administration 2

Common Pitfalls to Avoid

• Undertreatment risks include persistent hypothyroid symptoms, adverse effects on cardiovascular function, lipid metabolism, and quality of life 1
• Overtreatment can lead to iatrogenic hyperthyroidism, increasing risk for osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 1
• About 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH 1
• Dosages greater than 200 mcg/day are seldom required; inadequate response to daily dosages greater than 300 mcg/day may indicate poor compliance, malabsorption, or drug interactions 2
• Adjusting doses too frequently before reaching steady state (should wait 4-6 weeks between adjustments) 1

Factors Affecting Dosing Requirements

• Age and body weight 2
• Cardiovascular status 2
• Concomitant medical conditions including pregnancy 2
• Concomitant medications that may interfere with absorption 2, 5
• Co-administered food that may affect absorption 2
• Residual thyroid function 5, 6

By following these evidence-based guidelines for levothyroxine dosing, clinicians can effectively manage hypothyroidism while minimizing the risks of under or overtreatment.