Primary Hypothyroidism: Diagnosis and Treatment
Diagnosis
Low T3 with high TSH indicates primary hypothyroidism, where the thyroid gland is failing to produce adequate thyroid hormone. 1, 2
The diagnostic pattern shows:
- Elevated TSH (the pituitary is working overtime trying to stimulate the failing thyroid gland) 1, 2
- Low T3 (reflecting inadequate thyroid hormone production) 2
- Typically also low free T4, though you should measure this to distinguish overt from subclinical hypothyroidism 1, 3
Confirm the diagnosis by repeating TSH and measuring free T4 after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously. 1, 4 This critical step prevents unnecessary lifelong treatment for transient thyroiditis. 1
Consider measuring anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk (4.3% vs 2.6% per year in antibody-negative patients). 1, 2
Treatment Algorithm
When to Treat
Initiate levothyroxine therapy immediately for:
- TSH >10 mIU/L regardless of symptoms 1, 2, 3
- Any TSH elevation with low free T4 (overt hypothyroidism) 1, 2
- Symptomatic patients with any degree of TSH elevation 1, 3
- Pregnant women or those planning pregnancy with any TSH elevation 1, 2, 3
For TSH 4.5-10 mIU/L with normal free T4 (subclinical hypothyroidism), treatment decisions require individualization based on symptoms, positive anti-TPO antibodies, pregnancy plans, or infertility. 1, 2, 3
Levothyroxine Dosing
For patients <70 years without cardiac disease:
- Start with full replacement dose of 1.6 mcg/kg/day 1, 5, 2
- Titrate by 12.5-25 mcg increments every 4-6 weeks based on TSH 1, 5
For patients >70 years or with cardiac disease:
- Start with 25-50 mcg/day 1, 5, 2, 3
- Titrate more slowly every 6-8 weeks to avoid cardiac complications 1, 5
- Rapid normalization can unmask or worsen cardiac ischemia 1
Critical administration instructions:
- Take on empty stomach, 30-60 minutes before breakfast with full glass of water 1, 5
- Administer at least 4 hours apart from iron, calcium supplements, or antacids 1, 5
Monitoring Strategy
Recheck TSH and free T4 every 6-8 weeks during dose titration until TSH normalizes to 0.5-4.5 mIU/L. 1, 5, 2 The 6-8 week interval is critical because levothyroxine requires this time to reach steady state. 1, 4
Once stable, monitor TSH every 6-12 months or sooner if symptoms change. 1, 5
Free T4 helps interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize. 1
Critical Safety Considerations
Before initiating levothyroxine, rule out concurrent adrenal insufficiency (especially in suspected central hypothyroidism or hypophysitis), as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 6, 1, 2 Start physiologic dose steroids 1 week prior to thyroid hormone replacement if adrenal insufficiency is present. 6, 1
Avoid overtreatment: Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiovascular mortality. 1, 2, 4 Even slight overdose carries significant risk, especially in elderly and postmenopausal women. 1, 4
Common Pitfalls
Do not treat based on a single elevated TSH value without confirmation testing, as transient elevations are common. 1, 4 This prevents unnecessary lifelong treatment for transient thyroiditis. 1
Do not adjust doses too frequently before reaching steady state—wait the full 6-8 weeks between adjustments. 1, 4
Do not assume hypothyroidism is permanent without reassessment—consider transient causes like recovery from thyroiditis, acute illness, or medication effects. 1, 4
For elderly patients with cardiac disease, never start at full replacement dose, as this can precipitate myocardial infarction, heart failure, or fatal arrhythmias. 1, 3