What is the treatment for elevated Thyroid-Stimulating Hormone (TSH) levels?

Treatment for Elevated TSH

Initiate levothyroxine therapy for patients with TSH persistently >10 mIU/L or for symptomatic patients with any degree of TSH elevation. 1

Confirm the Diagnosis Before Treatment

• Repeat TSH testing after 3-6 weeks before initiating treatment, as 30-60% of elevated TSH levels normalize spontaneously on repeat testing 1, 2
• Measure both TSH and free T4 simultaneously to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 1, 3
• For patients with TSH 4.5-10 mIU/L and normal free T4, consider checking anti-TPO antibodies, as positive antibodies indicate higher progression risk (4.3% vs 2.6% per year) 1

Treatment Algorithm Based on TSH Level

TSH >10 mIU/L with Normal Free T4

• Start levothyroxine regardless of symptoms, as this level carries approximately 5% annual risk of progression to overt hypothyroidism 1, 4
• This threshold represents the clearest evidence for treatment benefit in preventing progression and complications 1

TSH 4.5-10 mIU/L with Normal Free T4

• Do not routinely treat asymptomatic patients in this range 1
• Consider treatment in specific situations: symptomatic patients with fatigue, weight gain, cold intolerance, or constipation; women planning pregnancy; patients with positive anti-TPO antibodies; or patients with goiter 1, 4
• Monitor TSH every 6-12 months without treatment if asymptomatic 1

Overt Hypothyroidism (Elevated TSH + Low Free T4)

• Initiate levothyroxine immediately for all patients with overt hypothyroidism 1, 3

Levothyroxine Dosing Strategy

For Patients <70 Years Without Cardiac Disease

• Start with full replacement dose of 1.6 mcg/kg/day based on ideal body weight 1, 5, 6
• Take on an empty stomach for optimal absorption 2

For Patients >70 Years OR With Cardiac Disease/Multiple Comorbidities

• Start with 25-50 mcg/day and titrate gradually to avoid cardiac decompensation 1, 5, 2
• Elderly patients with coronary disease are at increased risk of unmasking cardiac ischemia even with therapeutic levothyroxine doses 1
• Use smaller dose increments (12.5 mcg) in this population 1

For Pregnant Patients

• Treat any degree of TSH elevation in pregnancy, as subclinical hypothyroidism is associated with preeclampsia, low birth weight, and neurodevelopmental effects 1, 6
• For pre-existing hypothyroidism, increase levothyroxine dose by 25-50% as soon as pregnancy is confirmed 6
• Monitor TSH every 4 weeks during pregnancy to maintain trimester-specific reference ranges 6

Dose Adjustment and Monitoring

Initial Titration Phase

• Recheck TSH and free T4 every 6-8 weeks after starting therapy or changing dose 1, 6, 3
• Adjust dose by 12.5-25 mcg increments based on current dose and patient age 1
• Avoid larger adjustments that may lead to overtreatment, especially in elderly or cardiac patients 1

Maintenance Phase

• Once TSH is normalized (target 0.5-4.5 mIU/L), monitor TSH every 6-12 months 1, 6, 3
• Recheck sooner if symptoms change or new medications are started 1

Critical Pitfalls to Avoid

Do Not Treat Based on Single Elevated TSH

• 30-60% of elevated TSH levels normalize on repeat testing, representing transient thyroiditis in recovery phase 1, 2

Recognize and Avoid Overtreatment

• Approximately 25% of patients on levothyroxine are unintentionally overtreated with fully suppressed TSH 1
• Overtreatment increases risk for atrial fibrillation (especially in elderly), osteoporosis, fractures, and cardiac complications 1, 2, 4
• If TSH becomes suppressed (<0.1 mIU/L) on therapy, reduce dose by 25-50 mcg 1

Rule Out Adrenal Insufficiency First

• In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, start corticosteroids before levothyroxine to avoid precipitating adrenal crisis 1, 5

Account for Drug Interactions

• Iron, calcium, and proton pump inhibitors reduce levothyroxine absorption 2
• Enzyme inducers (phenytoin, carbamazepine, rifampin) increase levothyroxine metabolism 2
• Take levothyroxine at least 4 hours apart from these medications 1

Avoid Treating Elderly Patients Too Aggressively

• For patients >85 years with TSH ≤10 mIU/L, watchful waiting may be preferable to treatment 1
• Target slightly higher TSH ranges in very elderly patients to avoid overtreatment risks 1

Special Considerations

Patients on Immunotherapy

• Thyroid dysfunction occurs in 5-10% with anti-PD-1/PD-L1 therapy and 20% with combination immunotherapy 1
• Even subclinical hypothyroidism warrants treatment consideration if fatigue or other complaints are present 1

Patients with Cardiac Disease

• More frequent monitoring may be warranted—consider repeating TSH within 2 weeks of dose adjustment rather than waiting 6-8 weeks 1
• Start with lower doses (25-50 mcg/day) and titrate slowly 1, 2