What is the recommended starting dose of levothyroxine and titration schedule for a healthy adult (~60 kg) without cardiac disease, and how should the dosing be adjusted for patients over 65 years or with ischemic heart disease, arrhythmias, or heart failure?

Starting Dose of Levothyroxine

Healthy Adults Without Cardiac Disease (~60 kg)

For healthy adults under 65 years without cardiac disease, start levothyroxine at the full replacement dose of 1.6 mcg/kg/day (approximately 100 mcg daily for a 60 kg patient), as this rapidly normalizes thyroid function and prevents complications of untreated hypothyroidism. 1, 2

Initial Dosing Strategy

• Calculate the starting dose using actual body weight: 1.6 mcg/kg/day, which equals approximately 100 mcg daily for a 60 kg adult 1, 2
• Administer as a single daily dose on an empty stomach, 30–60 minutes before breakfast, to ensure optimal absorption 1, 2
• For obese patients, use ideal body weight rather than actual body weight for dose calculation 1

Titration Schedule

• Recheck TSH and free T4 at 6–8 weeks after initiating therapy, as this represents the time needed to reach steady-state concentrations 1, 2
• Adjust the dose by 12.5–25 mcg increments every 4–6 weeks based on TSH response until the patient is clinically euthyroid 1, 2
• Target TSH within the reference range of 0.5–4.5 mIU/L with normal free T4 levels 1
• Once stable, monitor TSH every 6–12 months or sooner if symptoms change 1

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Patients Over 65 Years or With Cardiac Disease

For patients over 65 years or those with ischemic heart disease, arrhythmias, or heart failure, start with a low dose of 25–50 mcg daily and titrate slowly by 12.5–25 mcg increments every 6–8 weeks to avoid precipitating myocardial infarction, heart failure, or life-threatening arrhythmias. 1, 2, 3

Modified Initial Dosing

• Begin at 25–50 mcg daily regardless of body weight in patients over 65 years 1, 2
• Use the same low starting dose (25–50 mcg daily) for any patient with cardiac disease, including those with ischemic heart disease, atrial fibrillation, heart failure, or coronary artery disease, regardless of age 1, 2
• For patients with recent acute coronary syndrome (e.g., NSTEMI), starting at 50 mcg carries unacceptable risk; begin at 25 mcg daily 1

Conservative Titration Approach

• Increase the dose by smaller increments of 12.5–25 mcg (preferably 12.5 mcg in very elderly or high-risk cardiac patients) every 6–8 weeks 1, 2
• Monitor TSH and free T4 at each dose adjustment interval (6–8 weeks) 1, 2
• Assess for new or worsening angina, palpitations, dyspnea, or arrhythmias at each follow-up visit 1
• Target TSH of 0.5–4.5 mIU/L; slightly higher targets (up to 5–6 mIU/L) may be acceptable in very elderly patients to reduce overtreatment risk 1

Physiologic Rationale

• Older adults require approximately one-third lower levothyroxine doses than younger populations (mean euthyroid dose of 1.09 mcg/kg actual body weight or 1.35 mcg/kg ideal body weight in those ≥65 years) 4
• Thyroid hormone metabolism slows with advancing age, reducing replacement requirements 5, 4
• Rapid normalization of thyroid hormone levels can unmask or worsen cardiac ischemia in patients with underlying coronary artery disease 1

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Critical Safety Considerations

• Before initiating levothyroxine in any patient, measure morning cortisol and ACTH to exclude adrenal insufficiency, as starting thyroid hormone before adequate corticosteroid coverage can precipitate life-threatening adrenal crisis 1
• Never start at full replacement dose in elderly patients or those with cardiac disease, as this can precipitate myocardial infarction, heart failure, or fatal arrhythmias 1
• Approximately 25% of patients on levothyroxine are unintentionally overtreated with suppressed TSH, increasing risks for atrial fibrillation (3–5 fold), osteoporosis, fractures, and cardiovascular mortality 1

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Common Pitfalls to Avoid

• Do not use the same starting dose for all patients; age and cardiac status mandate different approaches 1, 2
• Avoid adjusting doses more frequently than every 6–8 weeks, as steady-state is not reached before this interval 1, 2
• Do not treat based on a single elevated TSH value; confirm with repeat testing after 3–6 weeks, as 30–60% of elevated TSH levels normalize spontaneously 1
• Never assume that a normal-sized thyroid on examination excludes hypothyroidism; imaging has no role in diagnosis 1