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 and cardiac status. 1, 2, 3

Confirming the Diagnosis

Before initiating treatment, confirm the diagnosis with appropriate testing:

• Measure both TSH and free T4 to distinguish between overt hypothyroidism (elevated TSH with low free T4) and subclinical hypothyroidism (elevated TSH with normal free T4). 1, 2
• Repeat testing after 3-6 weeks if initial TSH is elevated, as 30-60% of elevated TSH values normalize spontaneously. 1
• Check anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk (4.3% vs 2.6% per year in antibody-negative patients). 1

Levothyroxine Dosing Strategy

For Younger Patients (<70 years) Without Cardiac Disease

• Start with full replacement dose of 1.6 mcg/kg/day to rapidly normalize thyroid function. 1, 4, 5
• This approach prevents prolonged exposure to hypothyroid symptoms and metabolic complications. 1

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

• Start with a lower dose of 25-50 mcg/day and titrate gradually to avoid cardiac complications. 1, 6, 3
• Elderly patients with coronary disease are at increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic levothyroxine doses. 1
• Atrial fibrillation is the most common arrhythmia observed with levothyroxine overtreatment in elderly patients. 6

Monitoring and Dose Adjustment

• Recheck TSH and free T4 every 6-8 weeks during dose titration until target TSH is achieved (0.5-4.5 mIU/L). 1, 2, 3
• Adjust dose in increments of 12.5-25 mcg based on current dose and patient characteristics. 1
• Use smaller increments (12.5 mcg) for elderly patients or those with cardiac disease; larger increments (25 mcg) may be appropriate for younger patients without comorbidities. 1
• Once stable, monitor TSH annually or sooner if symptoms change. 1, 2

Treatment Thresholds Based on TSH Level

TSH >10 mIU/L

• Initiate levothyroxine therapy regardless of symptoms, as this level carries approximately 5% annual risk of progression to overt hypothyroidism. 1, 3
• Treatment may improve symptoms, lower LDL cholesterol, and prevent cardiovascular complications. 1

TSH 4.5-10 mIU/L (Subclinical Hypothyroidism)

• Routine treatment is NOT recommended for most patients in this range. 1, 3
• Consider treatment in specific situations: symptomatic patients, pregnant women or those planning pregnancy, patients with positive anti-TPO antibodies, or those with goiter. 1, 3, 5
• Monitor thyroid function every 6-12 months without treatment if asymptomatic. 1

Special Populations

Pregnant Women

• Treat any degree of TSH elevation promptly, as maternal hypothyroidism is associated with preeclampsia, low birth weight, and potential neurodevelopmental effects in offspring. 1, 6
• Increase levothyroxine dose by 30% (take one extra dose twice weekly) as soon as pregnancy is confirmed. 6, 5
• Monitor TSH monthly during pregnancy and adjust dose to maintain TSH in normal range. 6
• Return to pre-pregnancy dose immediately after delivery. 6

Patients on Immunotherapy

• Consider treatment even for subclinical hypothyroidism if fatigue or other hypothyroid symptoms are present, as thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy. 1
• Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption. 1

Critical Safety Considerations

Rule Out Adrenal Insufficiency First

• In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, start corticosteroids BEFORE levothyroxine to prevent precipitating adrenal crisis. 1, 6

Avoid Overtreatment

• Approximately 25% of patients on levothyroxine are unintentionally maintained on excessive doses that fully suppress TSH. 1
• Overtreatment increases risk for atrial fibrillation (especially in elderly), osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy. 1, 6, 3
• TSH suppression (<0.1 mIU/L) significantly increases cardiovascular and bone risks and should be avoided unless treating thyroid cancer. 1

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH value without confirmation testing. 1
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism. 1
• Avoid excessive dose increases that could lead to iatrogenic hyperthyroidism. 1
• Do not adjust doses more frequently than every 6-8 weeks, as steady state is not reached before this time. 1
• Check for drug interactions that may affect levothyroxine absorption (calcium, iron, proton pump inhibitors, bile acid sequestrants) and administer levothyroxine at least 4 hours apart from these agents. 6

Administration Guidelines

• Take levothyroxine on an empty stomach, ideally 30-60 minutes before breakfast, for optimal absorption. 6
• Maintain consistent timing of administration to ensure stable thyroid hormone levels. 6