At what level of Thyroid-Stimulating Hormone (TSH) can we initiate levothyroxine (thyroxine) therapy?

When to Start Levothyroxine Based on TSH Levels

Levothyroxine therapy should be initiated in patients with TSH levels consistently above 10 mIU/L, even without symptoms, while patients with TSH between 4.5-10 mIU/L generally do not require routine treatment unless specific risk factors are present. 1, 2

Definite Indications for Levothyroxine Treatment

• Start levothyroxine in patients with TSH >10 mIU/L, even if asymptomatic, due to higher risk of progression to overt hypothyroidism (approximately 5% per year) 1, 2
• Treat all pregnant women or those planning pregnancy with levothyroxine regardless of TSH level to restore TSH to reference range, due to possible associations with fetal complications and neuropsychological issues in offspring 1, 2

TSH 4.5-10 mIU/L: Selective Treatment Approach

• Routine levothyroxine treatment is NOT recommended for patients with TSH 4.5-10 mIU/L who have normal free T4 levels 1, 2
• Consider a trial of levothyroxine in patients with TSH 4.5-10 mIU/L who have:
  • Symptoms compatible with hypothyroidism 1, 2
  • Positive thyroid peroxidase antibodies (anti-TPO), indicating autoimmune etiology and higher risk of progression to overt hypothyroidism (4.3% vs 2.6% per year) 2

Diagnostic Confirmation Before Treatment

• Confirm elevated TSH with repeat testing along with free T4 measurement within 2-3 months of initial assessment 1, 2
• This confirmation step is crucial as 30-60% of high TSH levels normalize spontaneously on repeat testing 3, 4

Age-Specific Considerations

• For elderly patients (>80-85 years) with TSH ≤10 mIU/L, a wait-and-see approach is generally preferred 5, 4
• Treatment may be harmful in elderly patients with subclinical hypothyroidism 4
• Consider age-specific TSH reference ranges: upper limit of normal is 3.6 mIU/L for patients under 40, and 7.5 mIU/L for patients over 80 4

Treatment Monitoring and Management

• When initiating therapy, start with 1.6 μg/kg/day in young adults (typically 75-100 μg/day for women and 100-150 μg/day for men) 6
• Use lower starting doses (12.5-50 μg/day) in elderly patients and those with coronary artery disease 3
• Recheck TSH 2 months after starting therapy and adjust dosage accordingly 5
• Target a stable serum TSH in the lower half of the reference range (0.4-2.5 mIU/L) for most adults 5
• Monitor TSH at least annually after stabilization 5

Common Pitfalls and Caveats

• Distinguishing true therapeutic effect from placebo effect in mild subclinical hypothyroidism can be challenging 1, 2
• Overzealous treatment of subclinical hypothyroidism may contribute to patient dissatisfaction, as symptoms rarely respond to treatment when hypothyroidism is minimal 4
• Even slight levothyroxine overdose carries risks of osteoporotic fractures and atrial fibrillation, especially in elderly patients 3
• Some medications (iron, calcium) reduce levothyroxine absorption, while enzyme inducers reduce its efficacy 3