At what dose should thyroxine (levothyroxine) be initiated for treatment of hypothyroidism?

Levothyroxine Initiation and Dosing for Hypothyroidism

When to Start Levothyroxine

Start levothyroxine immediately for patients with TSH persistently >10 mIU/L or for symptomatic patients with any degree of TSH elevation, as this threshold carries approximately 5% annual risk of progression to overt hypothyroidism. 1

Confirmation Before Treatment

• Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize spontaneously 1
• Measure both TSH and free T4 to distinguish subclinical hypothyroidism (normal free T4) from overt hypothyroidism (low free T4) 1
• Check anti-TPO antibodies to identify autoimmune etiology, which predicts higher progression risk (4.3% vs 2.6% per year in antibody-negative individuals) 1

Treatment Thresholds by TSH Level

• TSH >10 mIU/L: Initiate levothyroxine regardless of symptoms 1
• TSH 4.5-10 mIU/L: Consider treatment if symptomatic, pregnant/planning pregnancy, or positive anti-TPO antibodies 1
• Overt hypothyroidism (elevated TSH + low free T4): Start immediately without delay 1

Initial Levothyroxine Dosing

For patients <70 years without cardiac disease, start with full replacement dose of approximately 1.6 mcg/kg/day (typically 100-125 mcg/day for a 70 kg adult). 1, 2

Age and Cardiac Risk-Based Dosing Algorithm

Healthy patients <50 years:

• Start at full replacement dose: 1.6-1.8 mcg/kg/day 1, 2, 3
• This approach is safe and reaches euthyroidism faster than gradual titration 4

Patients 50-70 years OR <50 years with cardiac disease:

• Start at 25-50 mcg/day 1, 2
• Increase gradually at 6-8 week intervals 1, 2

Patients >70 years OR with significant cardiac disease:

• Start at 12.5-25 mcg/day 1, 2
• Increase gradually at 4-6 week intervals 2
• Older patients typically require less than 1 mcg/kg/day for maintenance 2, 5

Severe hypothyroidism (any age):

• Start at 12.5-25 mcg/day 2
• Increase by 25 mcg every 2-4 weeks with clinical and laboratory monitoring 2

Dose Adjustment Strategy

• Adjust in 12.5-25 mcg increments based on patient characteristics 1
• Use smaller increments (12.5 mcg) for elderly or cardiac patients 1
• Use larger increments (25 mcg) for younger patients without cardiac disease 1

Monitoring Protocol

Recheck TSH and free T4 every 6-8 weeks during dose titration until TSH normalizes to 0.5-4.5 mIU/L. 1, 2

• Once stable, monitor TSH every 6-12 months or if symptoms change 1
• For patients with cardiac disease or atrial fibrillation, consider more frequent monitoring within 2 weeks of dose adjustment 1

Critical Safety Considerations

Before Starting Levothyroxine

Always rule out concurrent adrenal insufficiency before initiating levothyroxine, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1

• In suspected central hypothyroidism or hypophysitis, start physiologic dose steroids 1 week prior to thyroid hormone 1

Risks of Overtreatment

• Approximately 25% of patients are inadvertently maintained on doses that fully suppress TSH 1
• Overtreatment increases risk for atrial fibrillation (especially in elderly), osteoporosis, fractures, and cardiac complications 1
• TSH suppression <0.1 mIU/L significantly increases cardiovascular and bone risks 1

Special Populations

Pregnancy

• Women with hypothyroidism who become pregnant should increase weekly dosage by 30% (take one extra dose twice per week) 3
• More aggressive TSH normalization is warranted, as subclinical hypothyroidism is associated with preeclampsia, low birth weight, and neurodevelopmental effects 1
• Monitor monthly during pregnancy 3

Patients on Immunotherapy

• Thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy and 16% with combination immunotherapy 1
• Consider treatment even for subclinical hypothyroidism if fatigue or other symptoms present 1
• Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption 1

Elderly with Cardiac Disease

• Elderly patients with coronary disease are at increased risk of cardiac decompensation even with therapeutic doses 1
• Start at 12.5-25 mcg/day and titrate slowly 1, 2
• Target TSH 0.5-4.5 mIU/L, though slightly higher targets may be acceptable in very elderly patients to avoid overtreatment risks 1

Common Pitfalls to Avoid

• Never treat based on single elevated TSH: 30-60% normalize on repeat testing 1
• Never assume hypothyroidism is permanent: Consider transient thyroiditis, especially in recovery phase 1
• Avoid excessive dose increases: Can lead to iatrogenic hyperthyroidism in 14-21% of patients 1
• Don't adjust doses too frequently: Wait 6-8 weeks between adjustments to reach steady state 1
• Never overlook adrenal insufficiency: Always rule out before starting levothyroxine 1