Thyroxine Dose Adjustment in Hypothyroidism
Initial Dosing Strategy
For patients under 50-70 years without cardiac disease, start levothyroxine at full replacement dose of approximately 1.6-1.7 mcg/kg/day (typically 100-125 mcg/day for a 70 kg adult), which safely achieves euthyroidism faster without cardiac risk. 1, 2, 3
For patients over 50-70 years OR with any cardiovascular disease, start at 25-50 mcg/day and increase gradually every 6-8 weeks. 1, 2, 4
- For elderly patients with cardiac disease specifically, the FDA recommends an even lower starting dose of 12.5-25 mcg/day with gradual increments at 4-6 week intervals 2, 5
- In severe hypothyroidism regardless of age, start at 12.5-25 mcg/day with increases of 25 mcg every 2-4 weeks 2
Critical Safety Consideration Before ANY Dose Initiation
Always rule out concurrent adrenal insufficiency before starting or increasing levothyroxine, as thyroid hormone can precipitate life-threatening adrenal crisis—if suspected, start corticosteroids at least 1 week before levothyroxine. 1, 6
Dose Adjustment Protocol
Adjust levothyroxine in 12.5-25 mcg increments based on TSH results, using smaller increments (12.5 mcg) for elderly or cardiac patients and larger increments (25 mcg) for younger healthy patients. 1, 2
Monitoring Timeline
- Recheck TSH and free T4 every 6-8 weeks after any dose change until TSH normalizes to 0.5-4.5 mIU/L 1, 2, 4
- For patients with cardiac disease or atrial fibrillation, consider more frequent monitoring within 2 weeks 1, 6
- Once stable, monitor TSH annually or sooner if symptoms change 1
Target TSH Levels
- Primary hypothyroidism: TSH 0.5-4.5 mIU/L with normal free T4 1, 2
- Pregnant women or planning pregnancy: TSH <2.5 mIU/L in first trimester 1, 4
- Elderly patients (>70 years): TSH up to 5-6 mIU/L may be acceptable to avoid overtreatment risks 1
Special Population Considerations
Cardiovascular Disease
Patients with known or suspected ischemic heart disease require conservative dosing starting at 12.5-25 mcg/day, as rapid normalization can unmask cardiac ischemia, precipitate angina, or trigger arrhythmias. 2, 5, 4
- Monitor closely for new or worsening angina, palpitations, dyspnea, or arrhythmias at each follow-up 1
- Obtain baseline ECG to screen for arrhythmias before initiating therapy 1
Pregnancy
Women with hypothyroidism who become pregnant should immediately increase their levothyroxine dose by 25-50% (take one extra dose twice weekly for total of 9 doses per week), followed by monthly TSH monitoring. 4, 7
- Levothyroxine requirements increase during pregnancy in nearly all women with pre-existing hypothyroidism 1, 4
- Target TSH <2.5 mIU/L in first trimester to prevent adverse pregnancy outcomes including preeclampsia, low birth weight, and neurodevelopmental effects 1, 4
Elderly Patients (>70 years)
Start at 25-50 mcg/day maximum, increase by 12.5 mcg increments every 6-8 weeks, and accept slightly higher TSH targets to minimize cardiac and bone risks. 1, 2, 5
- Elderly patients may require less than 1 mcg/kg/day for full replacement 2
- Age-adjusted TSH reference ranges shift upward, with upper limit reaching 7.5 mIU/L in patients over 80 1
Treatment Thresholds Based on TSH Level
TSH >10 mIU/L
Initiate levothyroxine therapy immediately regardless of symptoms or free T4 level, as this carries ~5% annual risk of progression to overt hypothyroidism and is associated with cardiovascular dysfunction. 1, 5
TSH 4.5-10 mIU/L (Subclinical Hypothyroidism)
Do NOT routinely treat, but consider treatment if: 1, 5
- Patient is symptomatic with fatigue, weight gain, cold intolerance, or constipation
- Positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk)
- Pregnant or planning pregnancy
- Patient preference after discussing uncertain benefits
Monitor TSH every 6-12 months without treatment if asymptomatic. 1
TSH <0.1 mIU/L (Overtreatment)
Reduce levothyroxine dose immediately by 25-50 mcg, as TSH suppression significantly increases risk of atrial fibrillation (3-5 fold), osteoporosis, fractures, and cardiovascular mortality. 1, 5, 4
- For TSH 0.1-0.45 mIU/L, reduce by 12.5-25 mcg, particularly in elderly or cardiac patients 1
Critical Pitfalls to Avoid
Do not treat based on a single elevated TSH—30-60% normalize spontaneously on repeat testing after 3-6 weeks. 1, 5
Approximately 25% of patients on levothyroxine are unintentionally overtreated with fully suppressed TSH, dramatically increasing serious complication risks. 1, 4
Never adjust doses more frequently than every 6-8 weeks, as levothyroxine requires 4-6 weeks to reach steady state. 1, 2
Avoid assuming hypothyroidism is permanent without reassessment—transient thyroiditis can cause elevated TSH that resolves spontaneously. 1, 5
Do not use combination T4/T3 therapy routinely, as levothyroxine monotherapy remains the standard of care with no proven benefit from adding T3. 4, 7
Administration and Drug Interactions
Take levothyroxine on an empty stomach, 30-60 minutes before breakfast, and at least 4 hours apart from iron, calcium supplements, or antacids which reduce absorption. 1, 2