When should levothyroxine (thyroid hormone replacement medication) be initiated in patients with hypothyroidism?

When to Start Levothyroxine Therapy in Hypothyroidism

Levothyroxine therapy should be initiated immediately in patients with elevated TSH whose free T4 concentration is below the reference range (overt hypothyroidism), while patients with subclinical hypothyroidism (elevated TSH with normal free T4) should be treated based on TSH levels, age, and clinical factors. 1, 2

Decision Algorithm for Initiating Levothyroxine

Overt Hypothyroidism

• Immediate treatment required when:
  • TSH is elevated AND free T4 is below reference range (0.8-2.0 ng/dL) 1
  • Hypothyroidism diagnosed during pregnancy 3
  • Congenital hypothyroidism (to prevent adverse effects on cognitive development) 3

Subclinical Hypothyroidism

• TSH >10 mIU/L:

  • Treatment recommended for patients under 65-70 years 4
  • Consider individual factors for patients >70 years

• TSH 4.5-10 mIU/L:

  • Treatment generally not routinely recommended 1
  • Consider treatment in:
    • Symptomatic patients (trial of therapy with clear symptom assessment)
    • Pregnant women or women planning pregnancy
    • Presence of thyroid antibodies (higher risk of progression)
    • Patients with cardiovascular risk factors or dyslipidemia

• Elderly patients (>80-85 years) with TSH ≤10 mIU/L:

  • Generally avoid treatment and use a wait-and-see approach 4
  • Start with lower doses if treatment is necessary 3

Monitoring After Diagnosis

• If initial TSH is elevated but free T4 is normal, repeat both measurements along with thyroid peroxidase antibodies after 2-3 months 4
• Monitor thyroid function tests at 6-12 month intervals in untreated subclinical hypothyroidism (TSH 4.5-10 mIU/L) 1

Special Populations

Pregnancy

• Hypothyroidism diagnosed during pregnancy should be promptly treated 3
• Monitor TSH and adjust dosage during pregnancy as requirements may increase 3
• Return to pre-pregnancy dose immediately after delivery 3

Elderly

• Start with lower doses (25-50 mcg/day) due to increased risk of cardiovascular disease 2, 3
• Target higher TSH range (1.0-4.0 mIU/L) compared to younger patients 2
• Monitor for atrial arrhythmias, which are more common with overtreatment 3

Cardiac Disease

• Start with lower doses (25-50 mcg/day) 2
• Target TSH range of 1.0-4.0 mIU/L 2

Important Considerations

• Before starting therapy:

  • Rule out or treat adrenal insufficiency to prevent precipitating adrenal crisis 2
  • Check for signs/symptoms of hypothyroidism, thyroid enlargement, family history 1
  • Review lipid profiles 1

• Administration guidelines:

  • Take on empty stomach, 30-60 minutes before breakfast with full glass of water 2
  • Avoid taking within 4 hours of calcium supplements, iron, or antacids 2

• Dosing approach:

  • Standard starting dose for most adults without cardiac disease: 1.6 mcg/kg/day 5
  • Women typically need 75-100 mcg/day, men 100-150 mcg/day 5
  • Lower starting doses for elderly or those with cardiac conditions 2, 3

• Target TSH ranges:

  • General population: 0.5-2.0 mIU/L 2
  • Elderly or cardiac patients: 1.0-4.0 mIU/L 2

• Follow-up:

  • Recheck TSH 6-8 weeks after starting therapy 2
  • If started for symptoms of subclinical hypothyroidism, reassess symptom improvement after 3-4 months of normalized TSH 4
  • If no symptom improvement, consider discontinuing therapy 4
  • Once stable, monitor TSH annually 4

Common Pitfalls to Avoid

• Overtreatment: Can cause thyrotoxicosis symptoms and atrial arrhythmias, especially in elderly 3
• Medication interactions: Separate administration from calcium, iron supplements, and antacids 2
• Poor adherence: About 28% of patients are non-adherent, missing at least 73 days per year 6
• Incorrect timing: Only 39% of patients take levothyroxine ≥30 minutes before eating as recommended 6
• Drug interactions: Beta-blockers (especially propranolol >160 mg/day) may decrease T4 to T3 conversion 2

By following this evidence-based approach to initiating levothyroxine therapy, clinicians can optimize treatment outcomes while minimizing risks of under- or over-treatment in patients with hypothyroidism.