Clinical meaning
Thyroid hormone therapy centers on replacing or supplementing endogenous T4 (thyroxine) and T3 (triiodothyronine) to restore euthyroid status. Levothyroxine (synthetic T4) is the mainstay of therapy because T4 serves as a prohormone that is peripherally converted to active T3 by type 1 and type 2 deiodinase enzymes in target tissues (liver, kidney, skeletal muscle, brain), providing a stable and physiologic T3 supply. The hypothalamic-pituitary-thyroid axis regulates this process: TRH from the hypothalamus stimulates TSH release from the anterior pituitary, which stimulates the thyroid. Exogenous T4 suppresses TSH through negative feedback, making TSH the primary monitoring parameter. Levothyroxine has a long half-life of 6-7 days, allowing once-daily dosing and stable serum levels. Bioavailability is approximately 70-80% when taken fasting, but decreases significantly with concurrent food, calcium, iron, aluminum-containing antacids, proton pump inhibitors, and soy products. Dose requirements are influenced by body weight (1.6 mcg/kg/day for full replacement), age, pregnancy (30-50% dose increase needed), and concurrent medications affecting thyroid hormone metabolism (phenytoin, carbamazepine, rifampin increase hepatic clearance; estrogen increases TBG requiring dose adjustment). In hypothyroid patients with coexisting adrenal insufficiency, glucocorticoid replacement...