Levothyroxine — Thyroid hormone / T4 replacement
Levothyroxine (synthetic L-thyroxine, T4) is the primary secretory product of the thyroid gland. T4 itself is largely inactive — it requires peripheral deiodination (by type 1 and type 2 deiodinase enzymes, DIO1/DIO2) to the active T3 (triiodothyronine) in liver, kidneys, and target tissues. T3 binds thyroid hormone receptors (TRα and TRβ) — nuclear receptors that regulate basal metabolic rate, cardiovascular function, neurological development, and thermogenesis. In hypothyroidism, insufficient T4/T3 leads to: fatigue, weight gain, bradycardia, constipation, cold intolerance, depression, hyperlipidemia, myopathy, and cognitive impairment. Levothyroxine monotherapy remains standard of care per ATA 2014, as peripheral T4→T3 conversion is highly efficient in most patients (though ~15% are poor DIO2 converters due to Thr92Ala polymorphism who may prefer T3 addition).
Overview
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Compound Class
Thyroid hormone / T4 replacement
Mechanism of Action
Levothyroxine (synthetic L-thyroxine, T4) is the primary secretory product of the thyroid gland. T4 itself is largely inactive — it requires peripheral deiodination (by type 1 and type 2 deiodinase enzymes, DIO1/DIO2) to the active T3 (triiodothyronine) in liver, kidneys, and target tissues. T3 binds thyroid hormone receptors (TRα and TRβ) — nuclear receptors that regulate basal metabolic rate, cardiovascular function, neurological development, and thermogenesis. In hypothyroidism, insufficient T4/T3 leads to: fatigue, weight gain, bradycardia, constipation, cold intolerance, depression, hyperlipidemia, myopathy, and cognitive impairment. Levothyroxine monotherapy remains standard of care per ATA 2014, as peripheral T4→T3 conversion is highly efficient in most patients (though ~15% are poor DIO2 converters due to Thr92Ala polymorphism who may prefer T3 addition).
Regulatory Status
FDA-approved (NDA 021200 and others). Multiple branded (Synthroid, Tirosint, Levoxyl) and generic formulations. Note: brand-to-generic switches can affect TSH — maintain consistent formulation.
Evidence Level
Very High — decades of clinical use, multiple large RCTs. ATA 2014 guidelines designate as standard of care. Consistently one of the most prescribed medications in the world.