When do you start a patient on levothyroxine (thyroid hormone replacement therapy)?

When to Start Levothyroxine Therapy

Levothyroxine therapy should be initiated for patients with TSH persistently >10 mIU/L regardless of symptoms, or for symptomatic patients with any degree of TSH elevation. 1

Diagnostic Confirmation Before Starting Treatment

• Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize on repeat testing 1
• Measure both TSH and free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 1, 2
• Consider testing for thyroid peroxidase (TPO) antibodies to identify autoimmune etiology, which predicts higher risk of progression to overt hypothyroidism 1

Treatment Algorithm Based on TSH Levels

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

• Initiate levothyroxine therapy regardless of symptoms 1, 2
• This level of elevation carries higher risk of progression to overt hypothyroidism (approximately 5% per year) 1
• Treatment prevents complications of hypothyroidism in patients who progress 1

TSH >10 mIU/L with Low Free T4 (Overt Hypothyroidism)

• Initiate levothyroxine therapy immediately 1, 2, 3
• Untreated overt hypothyroidism can lead to serious complications including heart failure and myxedema coma 3

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

• Consider treatment in the following situations:
  • Symptomatic patients (fatigue, weight gain, cognitive issues, etc.) 1, 4
  • Patients with positive TPO antibodies 1
  • Patients with goiter 5
  • Patients with infertility 5
  • Women planning pregnancy or currently pregnant 1, 2
  • Patients <65 years old 6
• For asymptomatic patients without these risk factors, monitoring without treatment is reasonable 1, 6

Special Populations

Pregnant Women or Those Planning Pregnancy

• Initiate levothyroxine for any degree of TSH elevation 1, 2
• Subclinical hypothyroidism during pregnancy is associated with adverse outcomes including preeclampsia and low birth weight 1
• Monitor TSH every 6-8 weeks during pregnancy and adjust dose as needed 2

Elderly Patients (>70 years)

• For patients with TSH >10 mIU/L, treatment is still recommended but with more cautious dosing 1, 2
• For patients with TSH 4.5-10 mIU/L without symptoms, consider observation rather than treatment, especially in those >80-85 years 6, 7
• Treatment may be harmful in elderly patients with mild subclinical hypothyroidism 6

Patients with Cardiac Disease

• Start with lower doses and titrate more gradually to avoid cardiac complications 1, 2
• Monitor closely for signs of overtreatment, which can increase risk for atrial fibrillation 8

Levothyroxine Dosing Guidelines

• For patients <70 years without cardiac disease: Start with full replacement dose of approximately 1.6 mcg/kg/day 1, 2
• For patients >70 years or with cardiac disease: Start with lower dose of 25-50 mcg/day and titrate gradually 1, 2, 8
• Dose adjustments should be made in increments of 12.5-25 mcg 1
• Target TSH in the lower half of the reference range (0.5-2.0 mIU/L) for most adults 1, 7

Monitoring Protocol

• Check TSH every 6-8 weeks after starting treatment or changing dose until stabilized 1, 2
• Once stabilized, monitor TSH annually or if symptoms change 1, 2
• For patients started on treatment for symptoms of subclinical hypothyroidism, reassess after 3-4 months; if no improvement, consider discontinuing therapy 7

Common Pitfalls to Avoid

• Overtreatment occurs in approximately 14-21% of patients and increases risk for osteoporosis, fractures, and cardiac complications 1, 5
• Undertreatment risks persistent symptoms and adverse effects on cardiovascular function and quality of life 1
• Failure to recognize transient hypothyroidism may lead to unnecessary lifelong treatment 1
• Failing to check both TSH and FT4 in symptomatic patients may miss central hypothyroidism 2