What is the recommended dose of levothyroxine (T4) for a patient with subclinical hypothyroidism, considering factors such as age, cardiac disease, and history of adrenal insufficiency?

Levothyroxine Dosing for Subclinical Hypothyroidism

For patients under 70 years without cardiac disease or adrenal insufficiency, start levothyroxine at 1.6 mcg/kg/day; for those over 70 years or with cardiac disease, start at 25-50 mcg/day and titrate gradually every 6-8 weeks. 1, 2

Age and Cardiac Status Determine Starting Dose

Younger Patients (<70 years) Without Cardiac Disease

• Start with full replacement dose of approximately 1.6 mcg/kg/day 1, 2
• This aggressive approach is safe in younger patients without cardiovascular comorbidities 1
• Titrate by 12.5-25 mcg increments every 4-6 weeks based on TSH response 1, 2

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

• Start with 25-50 mcg/day to avoid unmasking cardiac ischemia or precipitating arrhythmias 1, 3, 2
• Use smaller increments (12.5 mcg) when titrating to avoid cardiac complications 1
• Titrate every 6-8 weeks rather than 4-6 weeks for added safety 1, 3
• Elderly patients with coronary disease face increased risk of cardiac decompensation even with therapeutic levothyroxine doses 1

Critical Safety Consideration: Adrenal Insufficiency

Before initiating levothyroxine in any patient with suspected central hypothyroidism or history of adrenal insufficiency, you must start corticosteroids first—waiting at least 1 week before adding thyroid hormone—to prevent life-threatening adrenal crisis. 1, 4

• Thyroid hormone increases cortisol metabolism, which can precipitate adrenal crisis if cortisol reserves are inadequate 1
• This applies particularly to patients with pituitary disease, autoimmune polyendocrine syndromes, or those on immunotherapy 1
• Check morning cortisol and ACTH if adrenal insufficiency is suspected 1

TSH-Based Treatment Thresholds

TSH >10 mIU/L

• Treat regardless of symptoms or age 1, 4, 5
• 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

• Treatment decisions require individualization based on specific factors 1, 5
• Treat if: pregnant or planning pregnancy, symptomatic with hypothyroid complaints, positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk), or presence of goiter 1, 4, 5
• Monitor without treatment if: asymptomatic, elderly (>80-85 years), and antibody-negative 1, 5

Monitoring and Titration Protocol

Initial Titration Phase

• Recheck TSH and free T4 every 6-8 weeks after each dose adjustment 1, 3, 2
• Peak therapeutic effect takes 4-6 weeks to manifest 3, 2
• Target TSH: 0.5-4.5 mIU/L with normal free T4 1, 5

Maintenance Phase

• Once stable, monitor TSH every 6-12 months 1
• Monitor sooner if symptoms change or new medications are started 1

Common Pitfalls to Avoid

Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, and cardiac complications. 1

• Never treat based on a single elevated TSH—30-60% normalize on repeat testing after 3-6 weeks 1
• Avoid excessive dose increases that could cause iatrogenic hyperthyroidism (occurs in 14-21% of treated patients) 1
• Do not adjust doses more frequently than every 6-8 weeks before steady state is reached 1, 3
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism 1, 4

Special Population: Pregnancy

• Women planning pregnancy require treatment at any TSH elevation, targeting TSH <2.5 mIU/L in first trimester 1, 6
• Increase pre-pregnancy levothyroxine dose by 25-50% immediately upon pregnancy confirmation 1, 6
• Monitor TSH every 4 weeks during pregnancy until stable, then each trimester 1, 6