What is the treatment for hypothyroidism?

Treatment of Hypothyroidism

First-Line Treatment

Levothyroxine (synthetic T4) monotherapy is the definitive treatment for hypothyroidism, regardless of etiology. 1, 2, 3

• Levothyroxine is the only FDA-approved thyroid hormone replacement and remains the standard of care for both primary and central hypothyroidism 4, 5
• This synthetic preparation is chemically identical to endogenous thyroxine produced by the thyroid gland 4
• Combination therapy with levothyroxine plus liothyronine (T3) has not demonstrated clear advantages over monotherapy and should not be routinely used 6

Initial Dosing Strategy

For Patients Under 70 Years Without Cardiac Disease

• Start with full replacement dose of 1.6 mcg/kg/day to rapidly normalize thyroid function 1, 3
• This approach prevents prolonged exposure to hypothyroid state and its cardiovascular consequences 1

For Elderly Patients (>70 Years) or Those With Cardiac Disease

• Start with 25-50 mcg/day and titrate gradually to avoid cardiac complications 1, 4, 2
• Elderly patients with coronary disease are at increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic levothyroxine doses 7, 1
• Atrial fibrillation is the most common arrhythmia observed with levothyroxine overtreatment in the elderly 4

Critical Safety Consideration

• In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, always initiate corticosteroids BEFORE starting levothyroxine to prevent adrenal crisis 1

Monitoring and Dose Adjustment

Initial Titration Phase

• Recheck TSH and free T4 every 6-8 weeks after initiating therapy or changing doses 1, 2, 5
• Adjust dose in increments of 12.5-25 mcg based on current dose and patient characteristics 1
• Larger adjustments risk overtreatment, particularly in elderly or cardiac patients 1

Target TSH Levels

• Goal TSH: 0.5-4.5 mIU/L for most patients with primary hypothyroidism 1, 5
• For central hypothyroidism, monitor free T4 levels (maintain in upper half of normal range) rather than TSH 5

Maintenance Monitoring

• Once TSH is stable at goal, recheck every 6-12 months or sooner if symptoms change 1, 2
• Approximately 25% of patients are inadvertently maintained on doses high enough to suppress TSH completely, increasing risks for osteoporosis, fractures, and cardiac complications 7, 1

Treatment Thresholds Based on TSH Levels

TSH >10 mIU/L with Normal Free T4 (Subclinical Hypothyroidism)

• Initiate levothyroxine therapy regardless of symptoms 1, 5
• This threshold carries approximately 5% annual risk of progression to overt hypothyroidism 1
• Treatment may prevent cardiovascular complications and improve lipid profiles 1

TSH 4.5-10 mIU/L with Normal Free T4

• Routine treatment is NOT recommended for asymptomatic patients 1
• Consider treatment in specific situations: 1, 5
  • Symptomatic patients (fatigue, weight gain, cognitive issues)
  • Women planning pregnancy or currently pregnant
  • Positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk) 1
  • Infertility or goiter present 5
• Monitor TSH at 6-12 month intervals if not treating 1

Overt Hypothyroidism (Elevated TSH + Low Free T4)

• Immediate treatment with levothyroxine is mandatory 2, 3
• Untreated overt hypothyroidism causes serious complications including heart failure, cardiovascular events, and myxedema coma (30% mortality) 2

Special Populations

Pregnancy and Women Planning Pregnancy

• Treat any degree of TSH elevation in pregnant women or those planning pregnancy 1, 4, 5
• Untreated hypothyroidism during pregnancy is associated with spontaneous abortion, preeclampsia, stillbirth, premature delivery, and impaired fetal neurocognitive development 4
• Levothyroxine requirements typically increase 25-50% during pregnancy 1
• Monitor TSH more frequently during pregnancy and adjust doses promptly 4
• Return to pre-pregnancy dose immediately after delivery 4

Patients on Immune Checkpoint Inhibitors

• Consider treatment for subclinical hypothyroidism if fatigue or hypothyroid symptoms present 1
• Thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy and 16% with combination immunotherapy 1
• Continue checkpoint inhibitor therapy in most cases; high-dose corticosteroids rarely required 1

Pediatric Patients

• Initiate levothyroxine immediately upon diagnosis of congenital hypothyroidism 4
• Rapid restoration of normal T4 is essential to prevent adverse effects on cognitive development and physical growth 4
• Monitor closely during first 2 weeks for cardiac overload and arrhythmias 4

Critical Pitfalls to Avoid

Overtreatment Risks

• Overtreatment occurs in 14-21% of treated patients and increases risk for: 1
  • Atrial fibrillation and cardiac arrhythmias (especially elderly)
  • Osteoporosis and fractures (especially postmenopausal women)
  • Ventricular hypertrophy and abnormal cardiac output 7, 1
• TSH suppression below 0.1 mIU/L significantly increases these risks 1

Undertreatment Risks

• Persistent hypothyroid symptoms including fatigue, weight gain, and cognitive impairment 1
• Adverse cardiovascular effects and abnormal lipid metabolism 1
• Increased risk of heart failure and cardiovascular mortality 2

Common Dosing Errors

• Never treat based on single elevated TSH value - 30-60% normalize on repeat testing after 3-6 weeks 1
• Avoid adjusting doses more frequently than every 6-8 weeks before reaching steady state 1
• Do not fail to distinguish between patients requiring TSH suppression (thyroid cancer) versus those who don't (primary hypothyroidism) 1

Drug Interactions and Absorption Issues

• If TSH remains elevated despite adequate replacement dose, evaluate for: 5
  • Poor medication compliance
  • Malabsorption issues
  • Drug interactions affecting levothyroxine absorption

Evidence Quality Considerations

The recommendation for levothyroxine as first-line therapy is supported by decades of clinical experience and FDA approval 4, though the 2000 FDA approval process did not include studies evaluating long-term adverse effects 7. The evidence for treating subclinical hypothyroidism with TSH >10 mIU/L is rated as "fair" by expert panels 1, while evidence for treating TSH 4.5-10 mIU/L remains less consistent, requiring individualized decision-making 1.