When and what dosage of medication, such as levothyroxine (thyroid hormone replacement) or methimazole (antithyroid medication), should be started in a patient with thyroid dysfunction, based on their thyroid function tests, including Thyroid-Stimulating Hormone (TSH) levels, age, and weight?

Managing Thyroid Dysfunction: When to Start Medication and Dosing Guidelines

Hypothyroidism: When to Start Levothyroxine

Start levothyroxine immediately for TSH >10 mIU/L regardless of symptoms, or for any TSH elevation with low free T4, or for symptomatic patients with any degree of TSH elevation. 1

Treatment Thresholds Based on TSH Levels

TSH >10 mIU/L:

• Initiate levothyroxine therapy regardless of age or symptoms 1
• This threshold 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 (Subclinical Hypothyroidism):

• Do NOT routinely treat - monitor TSH every 6-12 months instead 1
• Consider treatment if:
  • Pregnant or planning pregnancy (treat any TSH elevation, target <2.5 mIU/L in first trimester) 1, 2
  • Positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk) 1
  • Symptomatic with fatigue, weight gain, cold intolerance, or constipation 1
  • Infertility or goiter present 3

Critical First Step:

• Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% normalize spontaneously 1, 4
• Measure both TSH and free T4 to distinguish subclinical from overt hypothyroidism 1

Levothyroxine Dosing for Hypothyroidism

Age <70 years without cardiac disease:

• Start with full replacement dose: 1.6 mcg/kg/day 1, 5
• Titrate by 12.5-25 mcg increments every 6-8 weeks until TSH normalizes 1
• Target TSH: 0.5-4.5 mIU/L 1

Age >70 years OR cardiac disease OR multiple comorbidities:

• Start with 25-50 mcg/day 1, 5
• Titrate more slowly every 6-8 weeks 1
• Use smaller increments (12.5 mcg) to avoid cardiac complications 1

Pregnant patients with pre-existing hypothyroidism:

• Increase pre-pregnancy dose by 25-50% immediately upon pregnancy confirmation 1, 5
• Check TSH every 4 weeks until stable, then minimum once per trimester 1
• Target TSH <2.5 mIU/L in first trimester 1

Pediatric dosing (by age):

• 0-3 months: 10-15 mcg/kg/day 5
• 3-6 months: 8-10 mcg/kg/day 5
• 6-12 months: 6-8 mcg/kg/day 5
• 1-5 years: 5-6 mcg/kg/day 5
• 6-12 years: 4-5 mcg/kg/day 5

• 12 years (growth incomplete): 2-3 mcg/kg/day 5

• Growth complete: 1.6 mcg/kg/day 5

Monitoring Protocol

During dose titration:

• Recheck TSH and free T4 every 6-8 weeks after any dose adjustment 1
• Wait full 6-8 weeks before adjusting again - levothyroxine requires this time to reach steady state 1

Once stable:

• Monitor TSH every 6-12 months 1
• Recheck sooner if symptoms change 1

Critical Safety Considerations

Before starting levothyroxine:

• Rule out adrenal insufficiency - starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 1, 3
• In suspected central hypothyroidism, always start physiologic dose steroids 1 week prior to levothyroxine 1

Elderly patients with cardiac disease:

• Start at 12.5-25 mcg/day if recent cardiac events 1
• Obtain baseline ECG to screen for arrhythmias 1
• Monitor closely for angina, palpitations, or worsening heart failure 1

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Hyperthyroidism: When to Start Methimazole

Refer all patients with overt hyperthyroidism (suppressed TSH with elevated free T4/T3) for specialist management. 6

Methimazole Dosing (Adult)

Initial dosing based on severity:

• Mild hyperthyroidism: 15 mg/day divided into 3 doses at 8-hour intervals 7
• Moderately severe: 30-40 mg/day divided into 3 doses 7
• Severe hyperthyroidism: 60 mg/day divided into 3 doses 7

Maintenance dosing:

• 5-15 mg/day once control achieved 7

Pediatric dosing:

• Initial: 0.4 mg/kg/day divided into 3 doses at 8-hour intervals 7
• Maintenance: approximately half of initial dose 7

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Common Pitfalls to Avoid

Overtreatment risks:

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses that fully suppress TSH 1
• TSH <0.1 mIU/L increases risk of atrial fibrillation (3-5 fold), osteoporosis, fractures, and cardiovascular mortality 1
• If TSH <0.1 mIU/L: reduce levothyroxine by 25-50 mcg immediately 1
• If TSH 0.1-0.45 mIU/L: reduce by 12.5-25 mcg, especially in elderly or cardiac patients 1

Do NOT treat based on single abnormal TSH:

• 30-60% of elevated TSH values normalize on repeat testing 1, 4
• Always confirm with repeat testing after 3-6 weeks 1

Avoid treating elderly patients with mild TSH elevation:

• 12% of persons aged 80+ with no thyroid disease have TSH >4.5 mIU/L 4
• TSH reference range shifts upward with age 4
• For TSH 4.5-10 mIU/L in elderly: observe rather than treat unless symptomatic 4

Never adjust doses too frequently:

• Must wait 6-8 weeks between adjustments for levothyroxine to reach steady state 1
• Adjusting sooner leads to inappropriate dosing 1