Clinical meaning
Levothyroxine (synthetic T4) is the standard of care for hypothyroidism replacement therapy. Thyroxine (T4) is a prohormone that is peripherally converted to the active hormone triiodothyronine (T3) by type 1 and type 2 deiodinase enzymes in liver, kidney, and other tissues. T3 binds to nuclear thyroid hormone receptors with 10-15 times greater affinity than T4, activating gene transcription that regulates basal metabolic rate, thermogenesis, cardiac function, bone metabolism, and neurological development.
Full replacement dose of levothyroxine is approximately 1.6 mcg/kg/day of ideal body weight in adults, though individual requirements vary based on age, weight, degree of residual thyroid function, absorption factors, and concurrent medications. In the elderly (over 65) and patients with cardiovascular disease, the starting dose should be low (12.5-25 mcg daily) and titrated slowly every 6-8 weeks to avoid precipitating angina, arrhythmia, or myocardial infarction from the metabolic demands of thyroid hormone restoration.
Absorption of levothyroxine occurs primarily in the jejunum and ileum and requires an acidic gastric environment. Bioavailability is 60-80% on an empty stomach but decreases significantly with food, calcium supplements, iron supplements, proton pump inhibitors, sucralfate, and cholestyramine. The drug has a long half-life of 6-7 days, allowing once-daily dosing and providing stable serum levels.
TSH is the primary monitoring parameter because it reflects the integrated thyroid hormone effect on the hypothalamic-pituitary axis. The negative feedback loop works as follows: low T3/T4 levels stimulate TRH from the hypothalamus, which stimulates TSH from the anterior pituitary; adequate thyroid hormone levels suppress both TRH and TSH. TSH should be checked 6-8 weeks after any dose change (this interval allows the pituitary to equilibrate to the new thyroid hormone level). The goal TSH for most adults is 0.5-2.5 mIU/L, though the target may be higher (4-6 mIU/L) in elderly patients over 75 to avoid overreplacement.