What is the initial treatment for hypothyroidism?

Initial Treatment for Hypothyroidism

Levothyroxine (T4) monotherapy is the first-line treatment for hypothyroidism, with dosing tailored to age and cardiac status. 1, 2, 3, 4, 5

Diagnostic Confirmation Before Treatment

• Confirm the diagnosis with both TSH and free T4 levels to distinguish overt hypothyroidism (elevated TSH with low free T4) from subclinical hypothyroidism (elevated TSH with normal free T4). 1, 2
• In patients with suspected central hypothyroidism (low TSH with low free T4), evaluate for concurrent adrenal insufficiency before starting levothyroxine, as thyroid hormone can precipitate adrenal crisis. 6, 1
• If central hypothyroidism or hypophysitis is suspected, always initiate corticosteroids (hydrocortisone 15-20 mg in divided doses) several days before starting levothyroxine. 6

Initial Levothyroxine Dosing Algorithm

For Patients <70 Years Without Cardiac Disease

• Start with full replacement dose of 1.6 mcg/kg/day (or 1.5-1.8 mcg/kg/day). 1, 2, 4, 5
• This approach is appropriate for young, healthy patients without significant comorbidities. 6, 1
• Most patients can tolerate starting at the full calculated dose without gradual titration. 3, 5

For Patients >70 Years OR With Cardiac Disease

• Start with a lower dose of 25-50 mcg/day and titrate gradually. 6, 1, 5
• This conservative approach prevents cardiac decompensation, as levothyroxine can unmask or worsen cardiac ischemia in elderly patients with underlying coronary disease. 1, 7
• Patients with atrial fibrillation, coronary artery disease, or multiple comorbidities require the lower starting dose. 1, 3, 5

For Patients With Long-Standing Severe Hypothyroidism

• Start at lower doses (25-50 mcg/day) even in younger patients, as rapid correction can precipitate cardiac complications. 3

Monitoring and Dose Adjustment

• Recheck TSH and free T4 in 6-8 weeks after initiating therapy or changing the dose. 6, 1, 7, 2
• Target TSH should be within the reference range of 0.4-4.5 mIU/L (or 0.5-2.0 mIU/L for optimal control). 1, 3
• If TSH remains above the reference range, increase levothyroxine dose by 12.5-25 mcg. 6, 1
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize. 1, 7

Long-Term Monitoring

• Once adequately treated with a stable dose, monitor TSH annually or every 6-12 months. 6, 1, 7, 2
• Recheck sooner if symptoms change or new medications are started that may affect thyroid hormone absorption or metabolism. 1, 8

Critical Safety Considerations

Drug Interactions to Avoid

• Administer levothyroxine at least 4 hours apart from phosphate binders (calcium carbonate, ferrous sulfate), bile acid sequestrants (cholestyramine, colesevelam), and ion exchange resins. 8
• Proton pump inhibitors, antacids, and sucralfate may reduce levothyroxine absorption by affecting gastric acidity. 8
• Phenobarbital, rifampin, phenytoin, and carbamazepine increase hepatic metabolism of levothyroxine, potentially requiring higher doses. 8

Monitoring for Overtreatment

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiac complications. 1, 3
• Development of low TSH (<0.1 mIU/L) on therapy indicates overtreatment; reduce dose by 12.5-25 mcg. 1
• Overtreatment is particularly dangerous in elderly patients and postmenopausal women due to increased fracture risk. 1, 3

Adjustments for Diabetes

• Levothyroxine may worsen glycemic control in patients with diabetes mellitus, requiring increased antidiabetic agent or insulin doses. 8
• Monitor blood glucose closely when starting, changing, or discontinuing thyroid therapy. 8

Adjustments for Anticoagulation

• Levothyroxine increases the response to oral anticoagulants; closely monitor coagulation tests and consider decreasing anticoagulant dose when correcting hypothyroidism. 8

Special Populations

Pregnant Women

• Women with hypothyroidism who become pregnant should increase their weekly levothyroxine dosage by 30% (take one extra dose twice per week) immediately upon pregnancy confirmation. 5
• Levothyroxine requirements typically increase by 25-50% during pregnancy. 1
• Monitor TSH monthly during pregnancy with more aggressive normalization targets to prevent adverse pregnancy outcomes including preeclampsia, low birth weight, and neurodevelopmental effects. 1, 5

Patients on Immune Checkpoint Inhibitors

• For immune checkpoint inhibitor-related hypothyroidism, levothyroxine can be started at full dose (1.6 mcg/kg) in young, healthy patients. 6
• Consider holding immune checkpoint inhibitors for grade ≥3 hypothyroidism until symptoms resolve to grade 2 or better. 6
• High-dose corticosteroids are not routinely required for immune checkpoint inhibitor-related hypothyroidism. 6

Common Pitfalls to Avoid

• Never start thyroid hormone before ruling out adrenal insufficiency in patients with suspected central hypothyroidism or hypophysitis. 6, 1
• Do not adjust doses more frequently than every 6-8 weeks, as steady state is not reached before this time. 1
• Avoid using combination levothyroxine plus liothyronine (T3) therapy, as there is no evidence of benefit even in patients with persistent symptoms. 5
• Do not treat based on a single elevated TSH value; 30-60% of elevated TSH levels normalize on repeat testing after 3-6 weeks. 1
• Failure to recognize transient hypothyroidism (such as after thyroiditis) may lead to unnecessary lifelong treatment. 1