Initial Levothyroxine Dosing for Hypothyroidism
For most adults under 60 years without cardiac disease, start levothyroxine at the full replacement dose of 1.6 mcg/kg/day, which safely achieves euthyroidism faster than low-dose titration regimens. 1, 2, 3
Age and Cardiac Risk-Based Dosing Algorithm
Younger adults (<60 years) without cardiac disease:
- Start at full replacement dose of 1.6 mcg/kg/day 1, 2, 4
- This approach is safe and reaches euthyroidism significantly faster than gradual titration (13 vs 1 patient euthyroid at 4 weeks in randomized trials) 3
- No increased cardiac events occur with full-dose initiation in cardiac asymptomatic patients 3
Elderly patients (>60-70 years) OR patients with cardiac disease:
- Start at 25-50 mcg/day 1, 5, 2, 4
- Titrate by 12.5-25 mcg increments every 6-8 weeks 1, 5
- Lower starting doses prevent unmasking or worsening cardiac ischemia, arrhythmias, or heart failure 1, 6, 4
- Elderly patients with coronary disease face increased risk of cardiac decompensation even with therapeutic levothyroxine doses 1
Patients with atrial fibrillation:
- Start at 25-50 mcg/day 5, 2
- Titrate more slowly (every 6-8 weeks) to avoid exacerbation of arrhythmias 1, 2
Monitoring and Titration Protocol
Initial monitoring:
- Check TSH and free T4 after 6-8 weeks of therapy 1, 5, 7, 4
- Adjust dose by 12.5-25 mcg increments every 4-6 weeks until euthyroid 1, 5, 2
- Peak therapeutic effect may not occur for 4-6 weeks after dose adjustment 2
Target TSH levels:
- For primary hypothyroidism: TSH 0.5-4.5 mIU/L with normal free T4 1, 8
- For central hypothyroidism: Use free T4 (not TSH) to guide therapy, targeting upper half of normal range 5, 2, 8
Long-term monitoring:
- Once stable, check TSH annually 1, 5, 7
- Recheck sooner if symptoms change or new medications are started 1
Critical Safety Considerations
Rule out adrenal insufficiency first:
- In patients with suspected central hypothyroidism or autoimmune disease, always start corticosteroids before levothyroxine to prevent life-threatening adrenal crisis 1
- Wait at least 1 week after starting steroids before initiating thyroid hormone 1
Avoid overtreatment:
- Approximately 25% of patients are unintentionally maintained on excessive doses that fully suppress TSH 1, 7
- Even slight overdose increases risk of atrial fibrillation (5-fold in patients ≥45 years with TSH <0.4 mIU/L) and osteoporotic fractures 1, 6
- TSH <0.1 mIU/L indicates overtreatment requiring immediate dose reduction by 25-50 mcg 1
Administration Instructions
Timing and absorption:
- Take on empty stomach, 30-60 minutes before breakfast 1, 2, 4
- Separate from iron, calcium supplements, or antacids by at least 4 hours 1
- Certain foods (soybean-based products) decrease absorption and may require dose adjustment 2
For patients who cannot swallow tablets:
- Crush tablet and suspend in 5-10 mL water 2
- Administer immediately by spoon or dropper 2
- Do not store suspension or mix with foods that decrease absorption 2
Special Populations
Pregnant patients:
- Increase pre-pregnancy dose by 25-50% immediately upon pregnancy confirmation 1, 4
- Target TSH <2.5 mIU/L in first trimester 1
- Monitor TSH every 4 weeks until stable, then at minimum once per trimester 1
- Untreated hypothyroidism increases risk of preeclampsia, low birth weight, and neurodevelopmental deficits 1, 4
Pediatric patients (0-3 months):
- Start at 10-15 mcg/kg/day 2
- For those at risk for cardiac failure, start lower and increase every 4-6 weeks 2
Common Pitfalls to Avoid
- Never treat based on single elevated TSH: 30-60% of elevated TSH values normalize spontaneously on repeat testing 1, 6
- Don't use standard doses in elderly cardiac patients: Starting at full replacement dose risks myocardial infarction, heart failure, or fatal arrhythmias 1
- Avoid adjusting doses too frequently: Wait full 6-8 weeks between adjustments to reach steady state 1
- Don't ignore inadequate response to >300 mcg/day: This suggests poor compliance, malabsorption, or drug interactions rather than need for higher doses 2, 8