When to start levothyroxine (T4) in subclinical hypothyroidism?

When to Start Levothyroxine in Subclinical Hypothyroidism

Levothyroxine treatment should be initiated in subclinical hypothyroidism when TSH is >10 mIU/L, when symptoms of hypothyroidism are present with TSH <10 mIU/L, in pregnant women or those planning pregnancy, or when TPO antibodies are significantly elevated (>500 IU/mL). 1

Definition and Diagnosis

Subclinical hypothyroidism is defined as:

• Elevated TSH above reference range (typically >4.5 mIU/L)
• Normal free T4 levels
• May be asymptomatic or present with mild symptoms

Treatment Algorithm

Definite Treatment Indications (Start Levothyroxine)

1. TSH >10 mIU/L regardless of symptoms 1, 2, 3
2. Pregnant women or planning pregnancy (any TSH elevation) 1, 4
3. Significant TPO antibody elevation (>500 IU/mL) 1

Consider Treatment (Trial of Levothyroxine)

1. TSH 4.5-10 mIU/L with hypothyroid symptoms 1, 5
   • Evaluate response after 3-4 months
   • Discontinue if no symptom improvement
2. TSH 4.5-10 mIU/L with infertility 2
3. TSH 4.5-10 mIU/L with goiter 6
4. TSH 4.5-10 mIU/L with elevated lipids or other cardiovascular risk factors 6

Observation Without Treatment

1. Elderly patients (>80-85 years) with TSH ≤10 mIU/L 5
   • Use age-specific reference ranges
   • "Wait-and-see" approach recommended
2. Asymptomatic patients with TSH 4.5-10 mIU/L without risk factors 3, 7
   • Monitor TSH annually

Treatment Approach

Initial Dosing

• Young adults without cardiovascular disease: 1.5-1.8 μg/kg/day 1, 3
• Elderly patients (>60 years) or those with coronary artery disease: Start low at 12.5-50 μg/day 1, 3
• Pregnant patients with new-onset hypothyroidism:
  • TSH ≥10 IU/L: 1.6 mcg/kg/day
  • TSH <10 IU/L: 1.0 mcg/kg/day 4

Monitoring and Dose Adjustment

• Check TSH 6-8 weeks after starting treatment or dose change 1, 4
• Adjust dose in 12.5-25 mcg increments 1
• Target TSH in lower half of normal range (0.5-2.5 mIU/L) 1, 5
• Once stable, monitor TSH annually 1, 5

Special Considerations

Pregnancy

• Increase levothyroxine dose by 30% as soon as pregnancy is confirmed 4, 3
• Monitor TSH every trimester and maintain within trimester-specific reference ranges 1, 4
• Return to pre-pregnancy dose immediately after delivery 4

Elderly Patients

• More likely to progress to overt hypothyroidism 1
• Higher risk of adverse effects from overtreatment (atrial fibrillation, decreased bone mineral density) 1, 7
• Use lower starting doses and titrate more slowly 3

Common Pitfalls

1. Overtreatment risks:

   • Subclinical hyperthyroidism occurs in 14-21% of treated patients 1
   • Increased risk of atrial fibrillation and osteoporosis 1, 7

2. Transient TSH elevation:

   • 30-60% of elevated TSH levels normalize on repeat testing 7
   • Always confirm abnormal TSH with repeat testing after 2-3 months 5

3. Treating based on TSH alone:

   • Consider complete clinical picture including symptoms 1
   • Normal or elevated T3 does not exclude hypothyroidism 1

4. Inadequate monitoring:

   • Failure to check for drug interactions (iron, calcium supplements reduce absorption) 7
   • Poor compliance or malabsorption may cause persistently elevated TSH 2

5. Failure to recognize adrenal insufficiency:

   • Screen for adrenal insufficiency in autoimmune thyroid disease 1
   • Untreated adrenal insufficiency is a contraindication to levothyroxine 4