How should levothyroxine (synthetic thyroxine) maintenance dose be initiated and titrated in a healthy adult, in patients over 65 or with coronary artery disease or heart failure, and in pregnant patients?

Levothyroxine Maintenance Dosing

Healthy Adults (Age <65–70, No Cardiac Disease)

Start levothyroxine at the full replacement dose of 1.6 mcg/kg/day in otherwise healthy adults under age 65–70 without cardiac disease 1, 2. This approach is safe, reaches euthyroidism faster, and avoids prolonged symptomatic hypothyroidism 3.

• Calculate the dose based on actual body weight (or ideal body weight in obese patients) 1
• A prospective randomized trial demonstrated that full-dose initiation in cardiac-asymptomatic patients caused no cardiac events and achieved euthyroidism significantly faster than low-dose titration (13 vs 1 patient euthyroid at 4 weeks, p=0.005) 3
• The typical full replacement dose ranges from 100–200 mcg/day, with doses >200 mcg/day rarely required 2

Monitor TSH and free T4 at 6–8 weeks after initiation, as levothyroxine requires 4–6 weeks to reach steady state 1, 2, 4. Adjust the dose by 12.5–25 mcg increments based on TSH results 1, 2. Once TSH normalizes to 0.5–4.5 mIU/L with normal free T4, recheck annually or sooner if symptoms change 1, 4.

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Patients Over Age 65–70 or With Coronary Artery Disease/Heart Failure

In elderly patients (>65–70 years) or those with any cardiac disease—including coronary artery disease, heart failure, or atrial fibrillation—start levothyroxine at a low dose of 25–50 mcg/day 1, 2, 4. Rapid normalization of thyroid hormone can unmask or worsen cardiac ischemia, precipitate myocardial infarction, trigger arrhythmias, or cause heart failure decompensation 1, 5.

• The lower starting dose applies regardless of age if cardiac disease is present 2
• Titrate slowly by 12.5–25 mcg increments every 6–8 weeks (not every 4 weeks as in younger patients) to minimize cardiovascular risk 1, 6, 2
• Elderly patients with underlying coronary disease are at increased risk of cardiac decompensation even with therapeutic levothyroxine doses 1
• Hypothyroidism itself causes cardiac dysfunction (delayed relaxation, reduced cardiac output, increased systemic vascular resistance), and in older patients with pre-existing heart disease, untreated hypothyroidism can worsen heart failure 1

Monitor TSH and free T4 every 6–8 weeks during titration 1, 6. For patients with atrial fibrillation, severe cardiac disease, or other serious medical conditions, consider repeating testing within 2 weeks of dose adjustment rather than waiting the full 6–8 weeks 1. Target TSH 0.5–4.5 mIU/L with normal free T4 1, 6, 4. Once stable, monitor annually 1, 4.

Critical Safety Consideration

Avoid TSH suppression (<0.1 mIU/L) in elderly and cardiac patients, as this increases the risk of atrial fibrillation 3–5 fold, accelerates bone loss, and raises cardiovascular mortality 1, 4. Approximately 25% of patients on levothyroxine are unintentionally overtreated with fully suppressed TSH 1, 4.

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Pregnant Patients

For women with pre-existing hypothyroidism who become pregnant, increase the levothyroxine dose by 25–50% immediately upon pregnancy confirmation 1, 2. Levothyroxine requirements typically rise during early pregnancy due to increased thyroid hormone metabolism and transfer to the fetus 1.

• Measure TSH and free T4 as soon as pregnancy is confirmed and at minimum once per trimester 1, 2
• Target TSH <2.5 mIU/L in the first trimester and within trimester-specific reference ranges thereafter 1, 2
• Adjust levothyroxine by 12.5–25 mcg increments based on TSH results 1
• Check TSH and free T4 every 4 weeks until stable, then at least once per trimester 1

For newly diagnosed hypothyroidism during pregnancy (TSH ≥10 mIU/L), start levothyroxine at 1.6 mcg/kg/day 1. Untreated maternal hypothyroidism increases the risk of preeclampsia, low birth weight, miscarriage, and permanent neurodevelopmental deficits in the child 1.

Use levothyroxine monotherapy only during pregnancy—do not use combination T4/T3 therapy, as T3 does not adequately cross the placenta to support fetal brain development 1.

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Common Pitfalls Across All Populations

• Never start levothyroxine before ruling out adrenal insufficiency in patients with suspected central hypothyroidism or hypophysitis, as thyroid hormone can precipitate life-threatening adrenal crisis 1, 6. If adrenal insufficiency is present, start hydrocortisone at least 1 week before levothyroxine 1
• Do not recheck TSH before 6–8 weeks after dose adjustment (4–6 weeks minimum), as steady state has not been reached 1, 2, 4
• Avoid excessive dose increases, which lead to iatrogenic hyperthyroidism in 14–21% of treated patients and increase risks of atrial fibrillation, osteoporosis, fractures, and cardiovascular mortality 1
• Confirm persistent TSH elevation with repeat testing after 3–6 weeks before initiating therapy, as 30–60% of elevated TSH values normalize spontaneously 1