What is the initial management for a patient with hypothyroidism (underactive thyroid), including the starting dose of levothyroxine (T4) and monitoring of thyroid-stimulating hormone (TSH) levels?

Initial Management of Hypothyroidism

Starting Levothyroxine Therapy

For newly diagnosed hypothyroid patients under 70 years without cardiac disease, start levothyroxine at the full replacement dose of 1.6 mcg/kg/day, taken on an empty stomach 30-60 minutes before breakfast. 1, 2, 3 This approach rapidly normalizes thyroid function and prevents complications such as cardiovascular dysfunction and adverse lipid profiles. 1

For patients over 70 years or those with cardiac disease, start with 25-50 mcg/day and titrate gradually every 6-8 weeks. 1, 2, 3 Rapid normalization can unmask or worsen cardiac ischemia, precipitate myocardial infarction, heart failure, or fatal arrhythmias in these high-risk populations. 1

Critical Safety Consideration Before Starting Treatment

Before initiating levothyroxine in any patient, rule out concurrent adrenal insufficiency—starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1, 2 If central hypothyroidism or hypophysitis is suspected, start physiologic dose steroids 1 week prior to thyroid hormone replacement. 1, 2

TSH Monitoring and Dose Titration

Recheck TSH and free T4 every 6-8 weeks after any dose adjustment until TSH normalizes within the reference range of 0.5-4.5 mIU/L. 1, 2, 3 The peak therapeutic effect of levothyroxine may not be attained for 4-6 weeks, making earlier testing inappropriate and likely to lead to incorrect dose adjustments. 1, 3

Adjust levothyroxine by 12.5-25 mcg increments based on TSH results and patient characteristics. 1, 2 Larger adjustments risk iatrogenic hyperthyroidism, which occurs in 14-21% of treated patients and increases risk for atrial fibrillation, osteoporosis, and cardiac complications. 1

Long-Term Monitoring

Once TSH is stable in the normal range, monitor annually or sooner if symptoms change. 1, 2 Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing serious complication risks. 1

Treatment Thresholds Based on TSH Level

Initiate levothyroxine therapy regardless of symptoms for patients with TSH >10 mIU/L, as this level carries approximately 5% annual risk of progression to overt hypothyroidism and is associated with increased cardiovascular risk. 1

For TSH 4.5-10 mIU/L with normal free T4 (subclinical hypothyroidism), treatment decisions should be individualized. 1 Consider treatment for:

• Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation 1
• Patients with positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk) 1
• Women planning pregnancy or currently pregnant 1

For TSH 4.5-10 mIU/L in asymptomatic patients without antibodies, monitor TSH every 6-12 months rather than treating. 1 Randomized controlled trials found no improvement in symptoms with levothyroxine therapy in this population. 1

Confirmation Testing Before Treatment

Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize spontaneously. 1, 4 Measure both TSH and free T4 to distinguish subclinical hypothyroidism (normal free T4) from overt hypothyroidism (low free T4). 1

Special Populations

Pregnant Patients

For pregnant patients with pre-existing hypothyroidism, increase levothyroxine by 25-50% immediately upon pregnancy confirmation. 1, 3, 5 Check TSH and free T4 as soon as pregnancy is confirmed and at minimum during each trimester, targeting TSH <2.5 mIU/L in the first trimester. 1, 3

Patients with Cardiac Disease

For patients with atrial fibrillation, cardiac disease, or serious medical conditions, consider more frequent monitoring within 2 weeks of dose adjustment rather than waiting 6-8 weeks. 1, 2 Start at 12.5-25 mcg/day in elderly patients with coronary disease to avoid cardiac decompensation. 1, 4, 5

Common Pitfalls to Avoid

Never treat based on a single elevated TSH value without confirmation, as transient elevations are common and may represent recovery from thyroiditis, acute illness, or medication effects. 1, 4

Avoid excessive dose increases that could lead to iatrogenic hyperthyroidism, which increases risk for osteoporosis, fractures, atrial fibrillation (5-fold increased risk in patients ≥45 years with TSH <0.4 mIU/L), and cardiovascular mortality. 1

Do not administer levothyroxine with foods that decrease absorption (soybean-based formulas, calcium, iron supplements, antacids)—maintain at least 4 hours separation. 1, 3