What is the recommended initial dose and titration schedule of levothyroxine (LT4) for hypothyroidism in adults, elderly patients with cardiac disease, children, and pregnant women?

Levothyroxine Dosing in 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 to achieve rapid normalization of thyroid function. 1, 2, 3

Adults Without Cardiac Disease (Age <70 years)

• Start at 1.6 mcg/kg/day as a single daily dose on an empty stomach, 30-60 minutes before breakfast 1, 2, 3
• This full replacement approach is safe in cardiac asymptomatic patients and achieves euthyroidism faster than low-dose titration (13 vs 1 patient euthyroid at 4 weeks) 3
• Adjust dose by 12.5-25 mcg increments every 6-8 weeks based on TSH response until TSH normalizes to 0.5-4.5 mIU/L 1, 2
• No cardiac events were documented with full-dose initiation in prospective trials of cardiac asymptomatic patients 3

Elderly Patients (Age >70) or Those With Cardiac Disease

For elderly patients or those with cardiac disease, start at 25-50 mcg/day and titrate slowly by 12.5-25 mcg increments every 6-8 weeks to avoid precipitating cardiac ischemia or arrhythmias. 1, 2, 4, 5

• The conservative approach is mandatory because rapid normalization can unmask or worsen cardiac ischemia, precipitate myocardial infarction, heart failure, or fatal arrhythmias 1, 5, 6
• Use 12.5 mcg increments (not 25 mcg) in very elderly or high cardiac risk patients 1
• Elderly patients with coronary disease are at increased risk of cardiac decompensation even with therapeutic levothyroxine doses 5
• Monitor closely for new or worsening angina, palpitations, dyspnea, or arrhythmias at each follow-up 5

Pediatric Dosing

Pediatric dosing is weight-based and decreases with age: 1, 2

• 0-3 months: 10-15 mcg/kg/day 1, 2
• 3-6 months: 8-10 mcg/kg/day 1, 2
• 6-12 months: 6-8 mcg/kg/day 1, 2
• 1-5 years: 5-6 mcg/kg/day 1, 2
• 6-12 years: 4-5 mcg/kg/day 1, 2
• >12 years (growth incomplete): 2-3 mcg/kg/day 1, 2
• Growth complete: 1.6 mcg/kg/day 1, 2

For infants 0-3 months at risk for cardiac failure, start at a lower dose and increase every 4-6 weeks 2

For children at risk for hyperactivity, start at one-fourth the recommended dose and increase weekly by one-fourth increments until full dose is reached 2

Pregnant Women

For pregnant women with pre-existing hypothyroidism, increase the levothyroxine dose by 25-50% immediately upon pregnancy confirmation. 1, 2

• Levothyroxine requirements increase by 25-50% during pregnancy in women with pre-existing hypothyroidism 1
• Target TSH <2.5 mIU/L in the first trimester and maintain within trimester-specific reference ranges 1, 2
• Check TSH and free T4 as soon as pregnancy is confirmed and at minimum during each trimester 2
• Monitor TSH every 4 weeks until stable, then at minimum once per trimester 1
• Untreated or inadequately treated maternal hypothyroidism increases risk of preeclampsia, low birth weight, and permanent neurodevelopmental deficits in the child 1

Monitoring and Titration Schedule

Recheck TSH and free T4 every 6-8 weeks after any dose adjustment until TSH reaches target range, as levothyroxine requires this interval to reach steady state. 1, 2

• The peak therapeutic effect of a given dose may not be attained for 4-6 weeks 2
• Once adequately treated, repeat TSH testing every 6-12 months or if symptoms change 1
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1

Target TSH Ranges

For primary hypothyroidism, target TSH within the reference range of 0.5-4.5 mIU/L with normal free T4. 1, 2

• For secondary or tertiary hypothyroidism, TSH is not reliable—use serum free T4 to titrate, targeting the upper half of the normal range 2
• For thyroid cancer patients, TSH targets vary by risk stratification and require endocrinologist consultation 1, 7

Critical Safety Considerations

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

• In patients with suspected central hypothyroidism or hypophysitis, start physiologic dose steroids 1 week prior to thyroid hormone replacement 1
• This is particularly important in patients on immune checkpoint inhibitors who may have hypophysitis 1

Common Pitfalls to Avoid

• Never adjust doses more frequently than every 6-8 weeks before reaching steady state 1
• Avoid excessive dose increases that could lead to iatrogenic hyperthyroidism, which occurs in 14-21% of treated patients and increases risk for atrial fibrillation, osteoporosis, and cardiac complications 1, 4
• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing serious complication risks 1
• Do not treat based on a single elevated TSH value—30-60% of elevated TSH levels normalize spontaneously on repeat testing 1, 4, 8
• For subclinical hypothyroidism (TSH 4.5-10 mIU/L with normal free T4), confirm diagnosis with repeat testing after 3-6 weeks, as 62% may revert to normal spontaneously 8

Special Populations Requiring Modified Approach

Subclinical Hypothyroidism

• Treat if TSH >10 mIU/L regardless of symptoms, as this carries approximately 5% annual risk of progression to overt hypothyroidism 1, 4
• For TSH 4.5-10 mIU/L, treatment is generally not recommended unless patient is symptomatic, pregnant, or has positive anti-TPO antibodies 1, 4, 8
• In double-blinded randomized controlled trials, treatment does not improve symptoms or cognitive function if TSH is less than 10 mIU/L 8

Patients on Immune Checkpoint Inhibitors

• 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 are present 1
• Monitor TSH every 4-6 weeks for the first 3 months, then every second cycle thereafter 1