levothyroxine

Levothyroxine is the synthetic form of thyroxine (T4), the primary drug used for hormone replacement in primary and secondary hypothyroidism, as well as for TSH suppression therapy in patients with differentiated thyroid cancer or nodules. Mechanism: T4 is a prohormone that is deiodinated peripherally (primarily in liver and kidney) to the more active T3, which binds nuclear thyroid hormone receptors (TRα and TRβ), forming a complex with retinoid X receptor (RXR) that regulates gene transcription. This increases basal metabolic rate, stimulates Na+/K+-ATPase activity, enhances catecholamine sensitivity, and supports normal growth, CNS development, and cardiovascular function. Clinical use: Dosing is weight-based (~1.6 mcg/kg/day) and titrated based on serial TSH levels (in primary hypothyroidism) or free T4 (in central hypothyroidism, since TSH is unreliable). It should be taken on an empty stomach, typically 30-60 minutes before breakfast, to maximize absorption. Absorption is impaired by calcium, iron, proton pump inhibitors, and fiber supplements. Levothyroxine has a long half-life (~7 days), allowing once-daily dosing and even missed-dose catch-up. Monitoring: TSH should be rechecked 4-6 weeks after any dose change, since it takes time to reach steady state. Elderly patients and those with cardiac disease should be started on lower doses to avoid precipitating angina or arrhythmias due to increased myocardial oxygen demand. Overtreatment can cause iatrogenic hyperthyroidism, presenting with tachycardia, weight loss, osteoporosis (due to increased bone turnover), and atrial fibrillation risk, especially in the elderly. Levothyroxine requirements increase during pregnancy (due to increased thyroid-binding globulin from estrogen) and in patients with malabsorption syndromes (e.g., celiac disease). Drug interactions: Levothyroxine increases warfarin's anticoagulant effect (by increasing clearance of clotting factors) and can affect insulin/oral hypoglycemic dosing requirements.