What is the recommended dose of levothyroxine (T4) for treating hypothyroidism?

Levothyroxine Dosing for Hypothyroidism

Initial Dosing Strategy

For adults under 70 years without cardiac disease, start with the full replacement dose of 1.6 mcg/kg/day, as this approach safely achieves euthyroidism faster without increasing cardiac risk. 1, 2, 3

Age and Cardiac Risk-Based Dosing

Adults <70 years without cardiac disease:

• Start with full replacement dose of 1.6 mcg/kg/day 1, 2
• Most patients require 100-150 mcg/day (median 125 mcg/day) 1, 4
• A prospective randomized trial demonstrated that full-dose initiation is safe and reaches euthyroidism significantly faster than low-dose titration (13 vs 1 patient euthyroid at 4 weeks, p=0.005) without any cardiac events 3

Adults >70 years or with cardiac disease/multiple comorbidities:

• Start with lower dose of 25-50 mcg/day 5, 1, 2
• Titrate more slowly every 6-8 weeks to avoid cardiac decompensation 1, 2
• Older patients require significantly less thyroxine (often 100 mcg/day or less, with some needing only 50 mcg/day) 6

Patients at risk for atrial fibrillation:

• Use lower starting doses (<1.6 mcg/kg/day) 2
• Titrate cautiously every 6-8 weeks 1, 2

Dose Titration Protocol

Adjust levothyroxine by 12.5-25 mcg increments every 4-6 weeks based on TSH and free T4 levels until the patient is euthyroid. 1, 2

• For younger patients without cardiac disease, use 25 mcg increments 1
• For elderly or cardiac patients, use smaller 12.5 mcg increments 1
• The peak therapeutic effect requires 4-6 weeks to manifest 2
• Larger adjustments risk overtreatment and should be avoided 1

Monitoring Guidelines

Check TSH every 6-8 weeks during dose titration, then every 6-12 months once stable. 1, 2

• For primary hypothyroidism, titrate until TSH normalizes (0.5-4.5 mIU/L) and patient is clinically euthyroid 1, 2
• For secondary/tertiary hypothyroidism, use free T4 (target upper half of normal range) rather than TSH for monitoring 2
• Free T4 helps interpret ongoing abnormal TSH during therapy, as TSH may lag behind 1

Special Population Considerations

Pregnant patients:

• Increase dose by 25-50% above pre-pregnancy requirements as soon as pregnancy is confirmed 1
• Monitor TSH and free T4 each trimester, maintaining TSH in trimester-specific reference range 2
• Inadequate treatment increases risk of preeclampsia, low birth weight, and neurodevelopmental effects 1

Pediatric patients (0-3 months):

• Start with 10-15 mcg/kg/day 2
• For those at risk for cardiac failure, use lower starting dose and increase every 4-6 weeks 2
• Titrate every 2 weeks based on TSH/free T4 2

Patients with TSH >10 mIU/L:

• Initiate treatment regardless of symptoms 1
• This threshold carries ~5% annual progression risk to overt hypothyroidism 1
• Confirm with repeat testing after 3-6 weeks, as 30-60% of elevations normalize spontaneously 1

Critical Pitfalls to Avoid

Never start levothyroxine before ruling out adrenal insufficiency in patients with suspected central hypothyroidism or hypophysitis, as this can precipitate life-threatening adrenal crisis. 5, 1

• Approximately 25% of patients are unintentionally overtreated with TSH suppression, increasing risks for atrial fibrillation, osteoporosis, and cardiac complications 1
• Avoid treating based on a single elevated TSH value without confirmation 1
• Do not adjust doses more frequently than every 4-6 weeks before reaching steady state 1
• Administer at least 4 hours before or after drugs that interfere with absorption 2

Treatment Goals and Overtreatment Risks

Target TSH of 0.5-4.5 mIU/L for primary hypothyroidism; TSH suppression (<0.1 mIU/L) indicates overtreatment requiring immediate dose reduction. 1

• Prolonged TSH suppression increases risk for atrial fibrillation (especially in elderly), osteoporosis, fractures, and cardiovascular mortality 1
• Overtreatment occurs in 14-21% of treated patients 1
• If TSH becomes suppressed, reduce dose by 12.5-25 mcg 1