When should thyroxine (T4) be initiated in a patient with hypothyroidism?

When to Initiate Thyroxine (Levothyroxine) Therapy

Initiate levothyroxine immediately for all patients with TSH persistently >10 mIU/L, regardless of symptoms, and for symptomatic patients with any degree of TSH elevation. 1

Confirmation Testing Before Treatment

• Always confirm elevated TSH with repeat testing after 2-3 months, as 30-62% of initially elevated TSH levels normalize spontaneously. 1, 2
• Measure both TSH and free T4 simultaneously to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4). 1
• For patients with cardiac disease, atrial fibrillation, or serious medical conditions, consider repeating testing within 2 weeks rather than waiting the full interval. 1

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L

• Start levothyroxine therapy immediately regardless of age, symptoms, or free T4 levels. 1, 3, 4
• This threshold carries approximately 5% annual risk of progression to overt hypothyroidism. 1
• Treatment prevents complications including cardiovascular dysfunction, metabolic derangements, and progression to myxedema coma. 1, 5

TSH 4.5-10 mIU/L (Subclinical Hypothyroidism)

• Treatment is NOT routinely recommended for asymptomatic patients in this range. 1, 6, 2
• DO treat if any of the following are present: 1, 4, 6
  • Symptomatic patients with fatigue, weight gain, cold intolerance, or cognitive complaints
  • Women who are pregnant or planning pregnancy
  • Positive anti-TPO antibodies (indicating autoimmune thyroiditis with 4.3% annual progression risk vs 2.6% without antibodies)
  • Presence of goiter
  • Infertility concerns
• For patients >80-85 years with TSH ≤10 mIU/L, avoid treatment and use watchful waiting strategy instead. 1, 6

TSH <4.5 mIU/L

• No treatment indicated unless secondary (central) hypothyroidism is suspected based on low free T4. 7

Initial Dosing Strategy

Young, Healthy Adults (<50-70 years without cardiac disease)

• Start with full replacement dose of 1.6 mcg/kg/day (typically 100-125 mcg/day for 70 kg adult). 1, 3, 7
• This approach is appropriate for otherwise healthy individuals recently treated for hyperthyroidism or hypothyroid for only a short time. 3

Elderly Patients (>70 years) or Those with Cardiac Disease

• Start with low dose of 25-50 mcg/day and titrate gradually every 6-8 weeks. 1, 3, 7
• For elderly patients with cardiac disease, consider even lower starting dose of 12.5-25 mcg/day. 3
• Titrate more slowly to avoid exacerbating cardiac symptoms, atrial fibrillation, or precipitating cardiac events. 3, 7, 5

Severe Hypothyroidism

• Start with 12.5-25 mcg/day with increases of 25 mcg every 2-4 weeks, accompanied by clinical and laboratory assessment. 3

Pregnant Patients

• For new-onset hypothyroidism with TSH ≥10 mIU/L: start 1.6 mcg/kg/day immediately. 7
• For pre-existing hypothyroidism, increase pre-pregnancy dose by 12.5-25 mcg/day as soon as pregnancy is confirmed. 7
• Monitor TSH every 4 weeks during pregnancy to maintain levels within trimester-specific reference ranges. 7

Critical Monitoring Parameters

• Recheck TSH and free T4 at 6-8 weeks after initiating therapy or changing dose, as peak therapeutic effect takes 4-6 weeks to manifest. 1, 3, 7
• Once stable, monitor TSH every 6-12 months or if symptoms change. 1
• Target TSH for primary hypothyroidism: 0.4-2.5 mIU/L (lower half of reference range). 6
• For secondary/tertiary hypothyroidism, target free T4 in upper half of normal range (TSH is unreliable). 3, 7

Critical Pitfalls to Avoid

• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism, as this can precipitate adrenal crisis. 1
• Avoid treating based on single elevated TSH value without confirmation testing. 1, 2
• Do not overtreat: approximately 25% of patients on levothyroxine are inadvertently maintained on excessive doses causing TSH suppression, increasing risks for atrial fibrillation (especially in elderly), osteoporosis, fractures, and cardiac complications. 1, 4
• Recognize that 14-21% of treated patients develop iatrogenic subclinical hyperthyroidism from overtreatment. 1
• Dosages >200 mcg/day are seldom required; inadequate response to ≥300 mcg/day suggests poor compliance, malabsorption, or drug interactions rather than need for higher dose. 3, 7

Special Populations Requiring Treatment

Pregnancy

• Treat all pregnant women with TSH above trimester-specific reference ranges to prevent preeclampsia, low birth weight, and neurodevelopmental effects in offspring. 1
• Levothyroxine requirements typically increase by 30-50% during pregnancy. 1

Positive Anti-TPO Antibodies

• Presence of anti-TPO antibodies with TSH >10 mIU/L is absolute indication for treatment due to higher progression risk (4.3% vs 2.6% annually). 1, 4

Cardiac Disease

• Subclinical hypothyroidism can cause delayed cardiac relaxation and abnormal cardiac output; treatment may improve cardiac function. 1
• However, use extreme caution with lower starting doses and slower titration to avoid exacerbating arrhythmias. 3, 7