How to treat subclinical hypothyroidism?

Treatment of Subclinical Hypothyroidism

Levothyroxine therapy should be initiated for patients with subclinical hypothyroidism and TSH levels consistently above 10 mIU/L due to higher risk of progression to overt hypothyroidism (5% per year). 1

Treatment Recommendations Based on TSH Levels

Definite Indications for Treatment:

• TSH consistently >10 mIU/L: Treat with levothyroxine regardless of symptoms 1, 2
• All pregnant women with subclinical hypothyroidism: Treat regardless of TSH level to reduce risks of pregnancy complications and potential adverse effects on fetal neurocognitive development 1, 3
• Patients with positive TPO antibodies and TSH >10 mIU/L: Treat due to higher risk of progression to overt hypothyroidism (4.3% vs 2.6% per year in antibody-negative individuals) 1, 2

Consider Treatment in TSH 4.5-10 mIU/L with:

• Symptomatic patients with symptoms compatible with hypothyroidism 1, 2
• Patients with positive TPO antibodies 1, 2
• Women planning pregnancy 2
• Patients with goiter or infertility 4

Monitoring Without Treatment (TSH 4.5-10 mIU/L):

• For patients with TSH between 4.5-10 mIU/L without risk factors, monitor thyroid function tests at 6-12 month intervals 1, 5
• Approximately 30-60% of elevated TSH levels may normalize spontaneously on repeat testing 6, 5

Treatment Protocol

Diagnostic Confirmation:

• Confirm diagnosis with repeat TSH and FT4 measurement after 2-3 months before initiating treatment 1, 2
• Measure both TSH and free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 2

Levothyroxine Dosing:

• For patients <70 years without cardiac disease: Start with full replacement dose of approximately 1.6 mcg/kg/day 2
• For patients >70 years or with cardiac disease: Start with a lower dose of 25-50 mcg/day and titrate gradually 2, 6
• For pregnant patients: Increase levothyroxine dosage by 12.5 to 25 mcg per day and monitor TSH every 4 weeks 3

Monitoring Protocol:

• Monitor TSH every 6-8 weeks while titrating hormone replacement 2
• Once adequately treated, repeat testing every 6-12 months or if symptoms change 2
• Target TSH level: 0.5-2.0 mIU/L for most patients 4
• For elderly patients, TSH goals are age-dependent with upper limits increasing with age (up to 7.5 mIU/L for patients over age 80) 6

Special Considerations

Elderly Patients:

• Treatment of subclinical hypothyroidism in patients >70 years with TSH <10 mIU/L should be approached cautiously 6
• Treatment may be harmful in elderly patients with subclinical hypothyroidism 6, 7
• For patients over 85 years, treatment should probably be avoided if TSH is <10 mIU/L 4

Pregnant Women:

• Treat all pregnant women with subclinical hypothyroidism 1, 3
• Monitor serum TSH and free-T4 at minimum during each trimester of pregnancy 3
• Return to pre-pregnancy levothyroxine dosage immediately after delivery 3

Common Pitfalls to Avoid

• Overtreatment risks development of subclinical hyperthyroidism in 14-21% of treated patients 1
• Iatrogenic hyperthyroidism increases risk for osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 2, 5
• About 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH 2
• Attributing non-specific symptoms to slightly elevated TSH may lead to unnecessary lifelong treatment 5
• Failure to recognize transient hypothyroidism may lead to unnecessary lifelong treatment 2, 5

Treatment Effectiveness

• In double-blinded randomized controlled trials, treatment does not improve symptoms or cognitive function if the TSH is less than 10 mIU/L 6
• Cardiovascular events may be reduced in patients under age 65 with subclinical hypothyroidism who are treated with levothyroxine 6, 7
• Limited evidence suggests that treatment of subclinical hypothyroidism in patients with TSH <10 mIU/L has tangible benefits 8, 5