How should levothyroxine (L‑T4) dosage be determined in hypothyroidism based on TSH and free T4 levels, taking into account the patient’s age, weight, and cardiac status?

Levothyroxine Dosing in Hypothyroidism Based on Thyroid Function Tests

For adults under 70 years without cardiac disease, start levothyroxine at the full replacement dose of approximately 1.6 mcg/kg/day, targeting a TSH of 0.5-4.5 mIU/L; for those over 70 or with cardiac disease, start at 25-50 mcg/day and titrate slowly by 12.5-25 mcg every 6-8 weeks based on TSH levels. 1, 2

Initial Dosing Strategy Based on Patient Characteristics

Younger Adults (<70 years) Without Cardiac Disease

• Start at full replacement dose: 1.6 mcg/kg/day of actual body weight 1, 2
• This aggressive approach is safe in this population and achieves target TSH faster 1
• For obese patients, consider using ideal body weight rather than actual weight, starting conservatively at 100-125 mcg daily 3

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

• Start low: 25-50 mcg/day regardless of TSH level 1, 2
• Rapid normalization can unmask cardiac ischemia, precipitate myocardial infarction, or trigger arrhythmias 1
• Even therapeutic doses carry risk in this population due to increased cardiac workload 1

Patients With Multiple Comorbidities

• Use the conservative 25-50 mcg/day starting dose 1
• Titrate more slowly (every 6-8 weeks rather than 4-6 weeks) 1

Dose Titration Algorithm Based on TSH Values

When TSH Remains Elevated (>4.5 mIU/L)

• Increase by 12.5-25 mcg increments 1, 2
• Use 25 mcg increments for younger patients without cardiac disease 1
• Use 12.5 mcg increments for elderly or cardiac patients 1
• Recheck TSH and free T4 after 6-8 weeks (the time required to reach steady state) 1

When TSH is Suppressed (<0.1 mIU/L)

• Decrease immediately by 25-50 mcg 1
• This indicates overtreatment and increases risk of atrial fibrillation (3-5 fold), osteoporosis, and cardiovascular mortality 1
• Approximately 25% of patients are unintentionally overtreated with fully suppressed TSH 1

When TSH is Low-Normal (0.1-0.45 mIU/L)

• Decrease by 12.5-25 mcg, especially in elderly or cardiac patients 1
• This range carries intermediate risk for atrial fibrillation and bone loss 1

When TSH is in Target Range (0.5-4.5 mIU/L)

• No dose adjustment needed 1
• Monitor TSH every 6-12 months once stable 1
• Check sooner if symptoms change or new medications are started 1

Special Considerations for Free T4 Interpretation

When TSH is Elevated but Free T4 is Normal

• This defines subclinical hypothyroidism 1
• If TSH >10 mIU/L: Treat regardless of symptoms (5% annual progression risk to overt hypothyroidism) 1
• If TSH 4.5-10 mIU/L: Consider treatment only if symptomatic, pregnant, or anti-TPO antibody positive 1

When TSH is Elevated and Free T4 is Low

• This defines overt hypothyroidism 1
• Always treat immediately with levothyroxine 1
• Start at full replacement dose in young adults, low dose in elderly/cardiac patients 1, 2

When Free T4 Helps Interpret Abnormal TSH During Therapy

• Free T4 can clarify ongoing abnormal TSH levels during dose titration, as TSH may take longer to normalize than free T4 1
• In central hypothyroidism, TSH is unreliable—use free T4 to guide dosing, targeting the upper half of normal range 2

Critical Safety Precautions Before Starting Levothyroxine

Rule Out Adrenal Insufficiency First

• Always check morning cortisol and ACTH before initiating levothyroxine in suspected central hypothyroidism 1
• Starting thyroid hormone before adequate glucocorticoid coverage can precipitate life-threatening adrenal crisis 1
• If adrenal insufficiency is present, start hydrocortisone at least 1 week before levothyroxine 1

Confirm Persistent TSH Elevation

• Repeat TSH and free T4 after 3-6 weeks before starting treatment 1
• 30-60% of elevated TSH values normalize spontaneously 1, 4
• Transient causes include acute illness, recovery from thyroiditis, iodine exposure, or certain medications 1

Monitoring Protocol

During Dose Titration

• Recheck TSH and free T4 every 6-8 weeks after each dose adjustment 1, 2
• Do not adjust doses more frequently—levothyroxine requires this interval to reach steady state 1
• Measure both TSH and free T4 to distinguish adequate replacement from over/undertreatment 1

After Achieving Target TSH

• Monitor TSH every 6-12 months once stable 1
• Check sooner if symptoms develop, weight changes significantly, or new medications are started 1
• For pregnant women, check TSH every trimester as requirements typically increase 25-50% 1

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH—confirm with repeat testing 1
• Never start at full replacement dose in elderly or cardiac patients—this can cause myocardial infarction or fatal arrhythmias 1
• Never ignore suppressed TSH (<0.1 mIU/L)—this dramatically increases fracture and atrial fibrillation risk, especially in elderly patients 1
• Never adjust doses before 6-8 weeks—premature adjustments lead to inappropriate dosing 1
• Never assume hypothyroidism is permanent—37% of subclinical hypothyroidism cases normalize spontaneously 1, 4