What is the best course of action for a patient with elevated TSH and normal Free T4 levels who is currently taking levothyroxine (75 mcg)?

Increase Levothyroxine Dose Immediately

Your current levothyroxine dose of 75 mcg is insufficient—increase to 87.5-100 mcg daily and recheck TSH in 6-8 weeks. 1, 2

Why This Dose Adjustment is Necessary

Your TSH of 5.390 mIU/L exceeds the normal reference range (0.450-4.500 mIU/L) while your Free T4 remains normal at 1.46 ng/dL, indicating subclinical hypothyroidism with inadequate levothyroxine replacement. 1, 2

• Patients already on levothyroxine therapy with TSH in the 4.5-10 mIU/L range require dose adjustment to normalize TSH into the reference range (0.5-4.5 mIU/L). 1
• Recent evidence demonstrates that hypothyroid patients with TSH values outside the normal range have increased mortality risk, making normalization of TSH crucial even when Free T4 appears normal. 2, 3
• Your TSH of 5.39 mIU/L indicates the current 75 mcg dose is providing inadequate thyroid hormone replacement, and failure to adjust risks persistent hypothyroid symptoms, adverse cardiovascular effects, and abnormal lipid metabolism. 1

Specific Dose Adjustment Protocol

Increase levothyroxine by 12.5-25 mcg based on your current dose and clinical characteristics: 1, 2

• For patients under 70 years without cardiac disease: Increase by 25 mcg to 100 mcg daily (more aggressive titration is appropriate). 1
• For patients over 70 years or with cardiac disease/multiple comorbidities: Increase by 12.5 mcg to 87.5 mcg daily (smaller increments prevent cardiac complications). 1, 2

The recommended increment of 12.5-25 mcg prevents overtreatment while effectively normalizing thyroid function—larger adjustments risk iatrogenic hyperthyroidism, especially in elderly or cardiac patients. 1

Monitoring Timeline After Dose Adjustment

• Recheck TSH and Free T4 in exactly 6-8 weeks after increasing the dose, as this represents the time needed to reach steady state. 1, 2
• Target TSH: 0.5-4.5 mIU/L with normal Free T4 levels. 1, 2
• If TSH remains elevated after 6-8 weeks, continue adjusting by 12.5-25 mcg increments every 6-8 weeks until TSH normalizes. 1, 2
• Once TSH is stable in the target range, monitor annually or sooner if symptoms change. 1

Critical Pitfalls to Avoid

• Never wait longer than 6-8 weeks between dose adjustments—adjusting too frequently before steady state leads to inappropriate dosing. 1
• Avoid excessive dose increases—approximately 25% of patients on levothyroxine are unintentionally overtreated with fully suppressed TSH, increasing risks for atrial fibrillation (especially in elderly), osteoporosis, fractures, and cardiac complications. 1, 4
• Do not ignore persistent TSH elevation—even subclinical hypothyroidism in treated patients carries approximately 5% annual risk of progression to overt hypothyroidism and is associated with cardiovascular dysfunction. 1

Drug Interactions That May Affect Your Dose

Ensure levothyroxine is taken properly to maximize absorption: 5

• Take levothyroxine at least 30-60 minutes before breakfast on an empty stomach. 1
• Separate by at least 4 hours from calcium supplements, iron, antacids, proton pump inhibitors, or bile acid sequestrants—these medications bind levothyroxine and reduce absorption. 5
• If taking any enzyme-inducing medications (phenobarbital, rifampin, carbamazepine), you may require higher levothyroxine doses due to increased hepatic metabolism. 5

Special Considerations

• If you have cardiac disease or atrial fibrillation: Use the more conservative 12.5 mcg increment and consider repeating testing within 2 weeks rather than waiting 6-8 weeks. 1
• If planning pregnancy: More aggressive TSH normalization is warranted, targeting TSH <2.5 mIU/L, as subclinical hypothyroidism during pregnancy is associated with adverse outcomes including preeclampsia and low birth weight. 1
• If you have positive TPO antibodies: This confirms autoimmune thyroiditis (Hashimoto's) and predicts higher progression risk to overt hypothyroidism (4.3% per year vs 2.6% in antibody-negative individuals), further justifying prompt dose adjustment. 1