What is the initial treatment for hypothyroidism (underactive thyroid)?

Initial Treatment for Hypothyroidism

Levothyroxine monotherapy is the first-line treatment for hypothyroidism, with dosing tailored to patient age, cardiac status, and disease severity. 1, 2, 3

Diagnostic Confirmation Before Treatment

• Confirm the diagnosis with both elevated TSH and low free T4 to establish overt hypothyroidism 1, 2
• For elevated TSH alone, repeat testing after 3-6 weeks since 30-60% of elevated values normalize spontaneously 1
• Measure anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which accounts for up to 85% of cases in iodine-sufficient areas and predicts higher progression risk 1, 2
• In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, always start corticosteroids before levothyroxine to prevent adrenal crisis 1

Initial Levothyroxine Dosing Strategy

For Younger Patients (<70 years) Without Cardiac Disease

• Start with full replacement dose of 1.6 mcg/kg/day (approximately 1.5-1.8 mcg/kg/day) 1, 3, 4, 5
• This approach rapidly normalizes thyroid function and prevents prolonged exposure to hypothyroid complications 1
• Most young, otherwise healthy patients tolerate full-dose initiation without adverse effects 3

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

• Start with a lower dose of 25-50 mcg/day and titrate gradually 1, 3, 5
• Elderly patients and those with coronary artery disease risk cardiac decompensation, angina, or arrhythmias even with therapeutic levothyroxine doses 1
• Use smaller dose increments (12.5 mcg) in this population to avoid cardiac complications 1

For Patients With Long-Standing Severe Hypothyroidism

• Initiate at lower doses regardless of age due to increased sensitivity to thyroid hormone replacement 3
• Gradual titration prevents unmasking of underlying cardiac ischemia 1

Monitoring and Dose Adjustment

• Recheck TSH and free T4 every 6-8 weeks after initiating therapy or changing doses 1, 2, 5
• This 6-8 week interval represents the time needed to reach steady state 1
• Target TSH within the reference range of 0.5-4.5 mIU/L with normal free T4 levels 1, 3
• Adjust dose by 12.5-25 mcg increments based on patient characteristics and current dose 1
• Once stable, monitor TSH annually or sooner if symptoms change 1, 2

Treatment Thresholds Based on TSH Levels

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

• Initiate levothyroxine therapy regardless of symptoms 1, 3
• This threshold carries approximately 5% annual risk of progression to overt hypothyroidism 1
• Treatment may improve symptoms and lower LDL cholesterol 1

TSH 4.5-10 mIU/L with Normal Free T4 (Mild Subclinical Hypothyroidism)

• Routine treatment is not recommended; instead, monitor thyroid function every 6-12 months 1
• Consider treatment in specific situations: symptomatic patients, pregnancy or planning pregnancy, positive anti-TPO antibodies, or infertility 1, 3
• Evidence for treatment benefits in this range is less consistent, requiring individualized assessment 1

Special Populations

Pregnant Women or Those Planning Pregnancy

• Treat at any TSH elevation, as subclinical hypothyroidism is associated with preeclampsia, low birth weight, and potential neurodevelopmental effects in offspring 1, 5
• Women with pre-existing hypothyroidism should increase their levothyroxine dose by 30% (approximately two extra doses per week) upon pregnancy confirmation 1, 5
• Monitor monthly during pregnancy with more aggressive TSH normalization 1

Patients on Immune Checkpoint Inhibitors

• Thyroid dysfunction occurs in 5-10% with anti-PD-1/PD-L1 therapy and 20% with combination immunotherapy 1
• Consider treatment even for subclinical hypothyroidism if fatigue or other symptoms are present 1
• Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption 1

Critical Pitfalls to Avoid

• Never treat based on a single elevated TSH value without confirmation testing 1
• Never start levothyroxine before ruling out adrenal insufficiency in suspected central hypothyroidism 1
• Avoid overtreatment, which occurs in 14-21% of treated patients and increases risk for atrial fibrillation, osteoporosis, fractures, and cardiac complications 1, 3
• Approximately 25% of patients are unintentionally maintained on doses sufficient to fully suppress TSH, significantly increasing morbidity risks 1
• Do not assume hypothyroidism is permanent without reassessment; transient thyroiditis can cause temporary TSH elevation 1

Drug Interactions Requiring Dose Adjustment

• Separate levothyroxine from calcium, iron, phosphate binders, and bile acid sequestrants by at least 4 hours 6
• Proton pump inhibitors, sucralfate, and antacids may reduce absorption by decreasing gastric acidity 6
• Phenobarbital, rifampin, and phenytoin increase hepatic metabolism, requiring higher levothyroxine doses 6
• Monitor anticoagulation closely, as levothyroxine increases response to oral anticoagulants 6
• In patients with diabetes, monitor glycemic control closely as levothyroxine may worsen glucose control and increase insulin requirements 6

Long-Term Safety Considerations

• When properly dosed, levothyroxine is safe for lifelong use 1
• Primary risks stem from overtreatment rather than the medication itself at replacement doses 1
• Prolonged TSH suppression (<0.1 mIU/L) significantly increases risk for atrial fibrillation (especially in elderly), osteoporosis, fractures, and cardiovascular mortality 1
• Patients with chronically suppressed TSH should ensure adequate calcium (1200 mg/day) and vitamin D (1000 units/day) intake 1