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

Treatment for Elevated TSH Levels

For patients with elevated TSH, initiate levothyroxine therapy if TSH is persistently >10 mIU/L or if the patient is symptomatic at any TSH level, but always confirm the elevation with repeat testing after 3-6 weeks first, as 30-60% of elevated TSH levels normalize spontaneously. 1

Initial Diagnostic Confirmation

• Repeat TSH and free T4 testing after 3-6 weeks before making treatment decisions, since up to 62% of initially elevated TSH levels revert to normal without intervention 1, 2
• Measure both TSH and free T4 simultaneously to distinguish subclinical hypothyroidism (normal free T4) from overt hypothyroidism (low free T4) 1
• Check thyroid peroxidase (TPO) antibodies, as positive antibodies indicate autoimmune etiology with higher progression risk (4.3% per year vs 2.6% in antibody-negative patients) 1, 3

Treatment Algorithm Based on TSH Levels

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, as randomized controlled trials show no improvement in symptoms or cognitive function with treatment 1, 2
• Consider a 3-4 month trial of levothyroxine only if the patient has: 1
  • Clear hypothyroid symptoms (fatigue, weight gain, cold intolerance, constipation)
  • Positive TPO antibodies
  • Infertility concerns
  • Pregnancy planning or current pregnancy
• Discontinue levothyroxine if no symptom improvement after 3-4 months at target TSH 1, 3

Overt Hypothyroidism (Low Free T4)

• Treat immediately with levothyroxine regardless of TSH level 1

Levothyroxine Dosing Strategy

For Patients <70 Years Without Cardiac Disease

• Start with full replacement dose of 1.6 mcg/kg/day taken on empty stomach 1, 5
• This allows faster achievement of euthyroid state in low-risk patients 1

For Patients >70 Years OR With Cardiac Disease

• Start with 25-50 mcg/day and titrate gradually 1, 5
• Use smaller increments (12.5 mcg) to avoid precipitating cardiac complications, particularly atrial fibrillation 1
• Elderly patients have age-adjusted TSH reference ranges, with upper limit of normal reaching 7.5 mIU/L by age 80 2

Dose Adjustments

• Increase by 12.5-25 mcg based on current dose and patient age/comorbidities 1
• Larger adjustments risk iatrogenic hyperthyroidism with serious complications 1

Monitoring Protocol

During Dose Titration

• Recheck TSH and free T4 every 6-8 weeks after any dose change, given levothyroxine's long half-life 1, 5
• Target TSH in the lower half of reference range (0.4-2.5 mIU/L) for most adults 3
• Free T4 helps interpret discordant results, as TSH may lag behind T4 normalization 1

After Stabilization

• Monitor TSH every 6-12 months once stable dose achieved 1, 5
• Recheck sooner if symptoms change or new medications are started 1

Special Population Considerations

Pregnant Women or Planning Pregnancy

• Treat at any TSH elevation, as subclinical hypothyroidism increases risk of preeclampsia, low birth weight, and neurodevelopmental effects 1
• Pre-pregnancy levothyroxine dose typically increases 25-50% during pregnancy 5
• Monitor TSH every 4 weeks during pregnancy to maintain trimester-specific targets 5

Elderly Patients (>80-85 Years)

• Avoid treatment for TSH ≤10 mIU/L in the oldest patients, as treatment may cause more harm than benefit 1, 3
• Use "wait-and-see" strategy with monitoring every 6-12 months 3
• Treatment in elderly with subclinical hypothyroidism may increase cardiovascular events rather than reduce them 2

Critical Pitfalls to Avoid

Overtreatment Risks

• Approximately 25% of patients on levothyroxine are unintentionally overtreated with fully suppressed TSH 1
• TSH suppression (<0.1 mIU/L) significantly increases risk of: 1
  • Atrial fibrillation, especially in elderly
  • Osteoporosis and fractures, particularly in postmenopausal women
  • Left ventricular hypertrophy
  • Increased cardiovascular mortality

Treatment of Transient Hypothyroidism

• Many cases of elevated TSH represent transient thyroiditis in recovery phase that resolves spontaneously 6
• Failure to recognize transient hypothyroidism leads to unnecessary lifelong treatment 1
• This is why repeat testing before treatment initiation is mandatory 1, 2

Medication Interactions

• Iron and calcium supplements reduce levothyroxine absorption—separate by 4 hours 6
• Enzyme inducers (phenytoin, carbamazepine, rifampin) increase levothyroxine metabolism 6
• Proton pump inhibitors may impair absorption 7

Adrenal Insufficiency

• Never start levothyroxine before ruling out adrenal insufficiency, as thyroid hormone can precipitate adrenal crisis 1
• In patients with suspected central hypothyroidism, initiate corticosteroids first 1

When NOT to Treat

• Single elevated TSH without confirmation 1, 2
• TSH 4.5-10 mIU/L in asymptomatic patients without risk factors 1, 2
• Elderly patients (>80 years) with TSH <10 mIU/L 3, 2
• During acute non-thyroidal illness—recheck after recovery 1
• Recent iodine exposure (CT contrast)—wait 6-8 weeks and retest 1

Refractory Cases

If TSH remains elevated despite apparently adequate levothyroxine dose: 4

• First assess medication adherence—most common cause of treatment failure
• Verify patient takes levothyroxine on empty stomach, 30-60 minutes before food
• Review for interfering medications or supplements
• Consider malabsorption disorders (celiac disease, atrophic gastritis, inflammatory bowel disease)
• Alternative formulations (liquid levothyroxine) may improve absorption in select cases 7