What is the typical dosing of levothyroxine (T4) for primary hypothyroidism?

Levothyroxine Dosing for Primary Hypothyroidism

Initial Dosing Strategy

For adults under 70 years without cardiac disease, start levothyroxine at the full replacement dose of 1.6 mcg/kg/day, as this approach is safe, reaches euthyroidism faster, and is more cost-effective than gradual titration. 1, 2

Age and Cardiac Risk-Based Dosing

Younger adults (<50-70 years) without cardiac disease:

• Start at full replacement dose of 1.6 mcg/kg/day 3, 4, 1
• This typically translates to 100-150 mcg/day for most patients 5
• A prospective randomized trial demonstrated this full-dose approach is safe even in cardiac asymptomatic patients and achieves euthyroidism significantly faster (13/25 patients at 4 weeks vs 1/25 with low-dose approach) 2

Older adults (>50-70 years) or those with cardiac disease:

• Start with 25-50 mcg/day 3, 4, 1
• This cautious approach prevents exacerbation of underlying coronary artery disease and arrhythmias 4, 6
• Elderly patients with coronary disease face increased risk of cardiac decompensation even with therapeutic doses 3

Patients at risk for atrial fibrillation:

• Use lower starting doses (25-50 mcg/day) 1
• Titrate more slowly at 6-8 week intervals rather than 4-6 weeks 1

Dose Titration Protocol

Adjust levothyroxine in 12.5-25 mcg increments based on TSH response:

• For younger patients without cardiac disease, use 25 mcg increments 3, 1
• For elderly or cardiac patients, use smaller 12.5 mcg increments to minimize cardiovascular risk 3, 4
• Wait 4-6 weeks between dose adjustments in most patients, as peak therapeutic effect takes 4-6 weeks 1, 6
• For elderly or high-risk cardiac patients, extend intervals to 6-8 weeks 3, 1

Monitoring and Target Goals

Monitor TSH every 6-8 weeks during titration until stable, then every 6-12 months:

• Target TSH range is 0.4-4.5 mIU/L for primary hypothyroidism 3, 7
• Free T4 can help interpret ongoing abnormal TSH levels, as TSH may take longer to normalize 3
• Once adequately treated, repeat testing every 6-12 months or if symptoms change 3

Critical Safety Considerations

Always start corticosteroids several days before thyroid hormone in patients with suspected adrenal insufficiency to prevent precipitating adrenal crisis 8, 4

Avoid overtreatment, which occurs in approximately 25% of patients:

• TSH suppression (<0.1 mIU/L) increases risk for atrial fibrillation, osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 3, 4
• Even slight overdose carries significant risk, especially in elderly and postmenopausal women 3
• If TSH becomes suppressed during therapy, reduce dose by 12.5-25 mcg 3

Predicting Optimal Dose

Pretreatment TSH levels can predict final levothyroxine requirements:

• Higher pretreatment TSH correlates with higher final levothyroxine dose requirements 9, 5
• Most patients (65%) require 100-150 mcg/day as maintenance dose 5
• Doses greater than 200 mcg/day are seldom required 1
• Inadequate response to doses >300 mcg/day suggests poor compliance, malabsorption, or drug interactions 1

Common Pitfalls to Avoid

Undertreatment risks:

• Persistent hypothyroid symptoms, adverse cardiovascular effects, abnormal lipid metabolism, and reduced quality of life 4
• TSH persistently >10 mIU/L despite treatment indicates insufficient replacement requiring dose escalation 3, 4

Drug and food interactions:

• Iron and calcium supplements reduce gastrointestinal absorption of levothyroxine 6
• Soybean-based formulas decrease absorption 1
• Enzyme inducers reduce efficacy 6
• Take levothyroxine on an empty stomach 6

Dosing frequency errors:

• Adjusting doses too frequently before reaching steady state (should wait 4-6 weeks minimum between adjustments) 3, 6