When to start, stop, and follow up levothyroxine (thyroid hormone replacement therapy) therapy for hypothyroidism and what is the target Thyroid-Stimulating Hormone (TSH) level to aim for?

Levothyroxine Therapy: When to Start, Stop, Follow-up, and Target Goals

When to Start Levothyroxine

Start levothyroxine immediately for TSH >10 mIU/L regardless of symptoms, or for any TSH elevation with symptomatic hypothyroidism. 1

Confirmation Before Starting

• Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize spontaneously 1, 2
• Measure both TSH and free T4 to distinguish subclinical (normal free T4) from overt hypothyroidism (low free T4) 1

TSH-Based Treatment Algorithm

• TSH >10 mIU/L: Start treatment regardless of symptoms—this carries ~5% annual risk of progression to overt hypothyroidism 1, 3
• TSH 4.5-10 mIU/L: Start treatment if symptomatic, pregnant/planning pregnancy, or positive anti-TPO antibodies 1, 4
• TSH 4.5-10 mIU/L asymptomatic: Monitor without treatment in most cases, especially if age >80-85 years 1, 4

Initial Dosing

• Age <70 without cardiac disease: Start full replacement dose of 1.6 mcg/kg/day 1, 5
• Age >70 or cardiac disease: Start low at 25-50 mcg/day and titrate gradually 1, 5
• Pregnant patients with new hypothyroidism: 1.6 mcg/kg/day if TSH ≥10 mIU/L, or 1.0 mcg/kg/day if TSH <10 mIU/L 5

Critical Safety Consideration

Never start levothyroxine before ruling out adrenal insufficiency—this can precipitate adrenal crisis. Start corticosteroids first if concurrent adrenal insufficiency is suspected. 1

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Target TSH to Reach

The target TSH is 0.5-4.5 mIU/L for most adults, with optimal range in the lower half (0.5-2.5 mIU/L). 1, 4

Age-Specific Targets

• Age <40 years: Upper limit of normal is 3.6 mIU/L 6
• Age >80 years: Upper limit of normal is 7.5 mIU/L—slightly higher targets may be acceptable 6
• Pregnant patients: Maintain TSH in trimester-specific reference range (lower half preferred) 1, 5

Special Population Targets

• Thyroid cancer patients (high-risk): TSH <0.1 mIU/L 1, 7
• Thyroid cancer patients (intermediate-risk): TSH 0.1-0.5 mIU/L 1, 7
• Thyroid cancer patients (low-risk, disease-free): TSH 0.5-2.0 mIU/L 1, 7

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Follow-up and Monitoring Schedule

During Dose Titration

Recheck TSH and free T4 every 6-8 weeks after any dose change until target is reached. 1, 5

• Adjust dose by 12.5-25 mcg increments based on TSH response 1, 7
• Use smaller increments (12.5 mcg) for elderly or cardiac patients 1
• Wait full 6-8 weeks between adjustments—levothyroxine has long half-life 2

After Reaching Target (Stable Dose)

Once TSH is stable in target range, monitor every 6-12 months. 1, 5

• Recheck sooner if symptoms change 1
• Annual monitoring is minimum for stable patients 4

Special Monitoring Situations

• Pregnant patients: Check TSH every 4 weeks during pregnancy 5
• Cardiac disease/atrial fibrillation: Consider rechecking within 2 weeks if TSH severely suppressed 1
• Pediatric patients: Monitor at 2 and 4 weeks after initiation, then every 3-12 months 5

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When to Stop or Continue After Reaching Target

Do not stop levothyroxine once target TSH is reached—hypothyroidism typically requires lifelong treatment. 1, 8

Exceptions Where Stopping May Be Considered

• Transient hypothyroidism: If TSH normalized spontaneously on repeat testing before treatment started 1, 2
• Drug-induced hypothyroidism: May resolve after discontinuing causative medication 1
• Post-partum thyroiditis: May be transient—recheck 4-6 weeks after acute phase 1
• Recovery of thyroid function: If TSH becomes suppressed (<0.1 mIU/L) without dose increase, consider dose reduction or trial off therapy with close monitoring 1

Trial Discontinuation Protocol (If Considering)

• Only attempt in patients with subclinical hypothyroidism who were started on treatment for TSH 4.5-10 mIU/L 1
• Recheck TSH 4-6 weeks after discontinuation 1
• If TSH remains elevated >10 mIU/L, resume treatment 1

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Dose Adjustment When Target Not Reached

If TSH Remains Elevated on Treatment

• TSH >10 mIU/L on therapy: Increase dose by 25 mcg 7
• TSH 4.5-10 mIU/L on therapy: Increase dose by 12.5-25 mcg 1, 7
• First verify medication adherence and proper administration (take on empty stomach, 30-60 minutes before food) 1
• Check for interfering medications (iron, calcium, proton pump inhibitors) 1, 2

If TSH Becomes Suppressed (<0.1 mIU/L)

Reduce dose by 25-50 mcg immediately to avoid complications of iatrogenic hyperthyroidism. 1

• Prolonged TSH suppression increases risk of atrial fibrillation, osteoporosis, and cardiovascular mortality 1
• Recheck TSH in 6-8 weeks after dose reduction 1
• Exception: Thyroid cancer patients may require intentional TSH suppression—consult endocrinology 1, 7

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Common Pitfalls to Avoid

• Treating single elevated TSH without confirmation: 30-60% normalize spontaneously 1, 2
• Adjusting doses too frequently: Must wait 6-8 weeks for steady state 1
• Over-treatment: 25% of patients are maintained on excessive doses causing TSH suppression 1
• Ignoring age-specific targets: Elderly patients tolerate slightly higher TSH 6
• Starting thyroid hormone before addressing adrenal insufficiency: Can cause adrenal crisis 1
• Assuming all hypothyroidism is permanent: Some cases are transient and don't require lifelong treatment 1, 2