What is the initial treatment for hypothyroidism?

Initial Treatment for Hypothyroidism

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

Confirm the Diagnosis First

Before initiating treatment, confirm the diagnosis biochemically 1, 2:

• Overt primary hypothyroidism: Elevated TSH with low free T4 1, 2, 3
• Subclinical hypothyroidism: Elevated TSH (>4.5 mIU/L) with normal free T4 1, 4
• Repeat testing after 3-6 weeks if initial TSH is elevated, as 30-60% of elevated TSH levels normalize spontaneously 1

Critical safety step: Rule out concurrent adrenal insufficiency before starting levothyroxine, especially in suspected central hypothyroidism, as thyroid hormone can precipitate adrenal crisis 1, 2. Always start corticosteroids first if adrenal insufficiency is present 1, 2.

Initial Levothyroxine Dosing Strategy

For Patients <70 Years Without Cardiac Disease

• Start with full replacement dose: 1.6 mcg/kg/day based on ideal body weight 1, 2, 4, 5
• This approach rapidly normalizes thyroid function and prevents complications 1

For Patients >70 Years OR With Cardiac Disease OR Multiple Comorbidities

• Start low and go slow: 25-50 mcg/day 1, 2, 3, 6
• Titrate gradually every 6-8 weeks to avoid exacerbating angina, arrhythmias, or cardiac decompensation 1, 2, 6
• Elderly patients with coronary disease are at increased risk of cardiac complications even with therapeutic doses 1

For Pregnant Women or Those Planning Pregnancy

• Treat any degree of TSH elevation to prevent adverse pregnancy outcomes including preeclampsia, low birth weight, and neurodevelopmental effects 1
• Levothyroxine requirements increase by 25-50% during pregnancy 1
• More aggressive TSH normalization is warranted in this population 1

Monitoring and Dose Adjustment

• Recheck TSH and free T4 in 6-8 weeks after starting treatment or changing dose 1, 2, 3, 6
• Target TSH: 0.5-4.5 mIU/L with normal free T4 1, 4, 5
• Adjust dose in 12.5-25 mcg increments based on patient characteristics 1
• Use smaller increments (12.5 mcg) for elderly or cardiac patients 1
• Once stable, monitor TSH annually or sooner if symptoms change 1, 3

Treatment Thresholds Based on TSH Level

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

• Treat regardless of symptoms 1, 4
• This level 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)

• Do not routinely treat 1, 4
• Monitor TSH every 6-12 months 1
• Consider treatment in specific situations 1, 4:
  • Symptomatic patients (fatigue, weight gain, cold intolerance, constipation)
  • Positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk) 1
  • Women planning pregnancy 1
  • Patients with goiter 4

Critical Pitfalls to Avoid

• Never start thyroid hormone before corticosteroids in patients with suspected adrenal insufficiency—this can precipitate life-threatening adrenal crisis 1, 2
• Avoid treating based on a single elevated TSH without confirmation, as 30-60% normalize spontaneously 1
• Do not overtreat: 14-21% of treated patients develop iatrogenic hyperthyroidism, increasing risk for atrial fibrillation, osteoporosis, fractures, and cardiac complications 1
• Approximately 25% of patients on levothyroxine are unintentionally maintained on excessive doses that fully suppress TSH 1, 3
• Avoid excessive starting doses in elderly or cardiac patients—this can unmask or worsen cardiac ischemia 1

Drug Interactions Requiring Dose Adjustment

Levothyroxine absorption is reduced by 7:

• Phosphate binders (calcium carbonate, ferrous sulfate): Separate by at least 4 hours 7
• Bile acid sequestrants (cholestyramine, colesevelam): Separate by at least 4 hours 7
• Proton pump inhibitors, antacids, sucralfate: Monitor TSH appropriately 7

Levothyroxine metabolism is increased by 7:

• Phenobarbital, rifampin: May require increased levothyroxine dose 7

Monitor glycemic control closely when starting levothyroxine in patients with diabetes, as thyroid hormone may worsen glycemic control and increase insulin requirements 7.

Monitor anticoagulation closely when starting levothyroxine in patients on warfarin, as thyroid hormone increases anticoagulant response and may require dose reduction 7.

Why Levothyroxine Monotherapy?

• Levothyroxine (T4) is converted to the active hormone T3 in peripheral tissues 4, 5
• Adding T3 (liothyronine) is not recommended, even in patients with persistent symptoms and normal TSH 6
• Levothyroxine monotherapy remains the standard of care for both primary and central hypothyroidism 4