OnePin Peptide Library · Metabolic
T4 (Levothyroxine / Synthroid)
T4 · Synthroid · Levothroid · Levothyroxine Sodium
Levothyroxine sodium (T4) is the synthetic form of thyroxine, the primary storage hormone produced by the thyroid gland. It is converted peripherally in the liver, kidneys, and other tissues to the biologically active form, triiodothyronine (T3), via the deiodinase enzymes. Levothyroxine is one of the most prescribed medications in the world and is the first-line treatment for primary hypothyroidism. It is FDA-approved under brand names including Synthroid, Levoxyl, Tirosint, Euthyrox, and Unithroid.
Take in the morning on an empty stomach, 30-60 minutes before breakfast, calcium, iron supplements, or antacids, as these dramatically reduce absorption. Starting dose is typically 25-50 mcg/day for adults without cardiac disease, with 12.5 mcg increments every 4-6 weeks based on TSH response. Do not expect to feel a change for the first 1-2 weeks - T4 takes 4-6 weeks to reach new steady state.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
How it works
Levothyroxine is identical to endogenous T4. It serves as the circulating storage form of thyroid hormone and is converted to the active T3 by peripheral deiodinase enzymes (predominantly type 1 and type 2 deiodinases) in the liver, kidneys, pituitary, thyroid, skeletal muscle, and brain. The resulting T3 binds nuclear thyroid hormone receptors (TR-alpha and TR-beta), regulating transcription of genes controlling basal metabolic rate, oxygen consumption, protein turnover, carbohydrate and lipid metabolism, and thermogenesis.
Levothyroxine is identical to endogenous T4. It serves as the circulating storage form of thyroid hormone and is converted to the active T3 by peripheral deiodinase enzymes (predominantly type 1 and type 2 deiodinases) in the liver, kidneys, pituitary, thyroid, skeletal muscle, and brain. The resulting T3 binds nuclear thyroid hormone receptors (TR-alpha and TR-beta), regulating transcription of genes controlling basal metabolic rate, oxygen consumption, protein turnover, carbohydrate and lipid metabolism, and thermogenesis.
The long plasma half-life (approximately 7 days) reflects high-affinity binding to thyroxine-binding globulin (TBG), transthyretin, and albumin. This binding pool buffers daily fluctuations and produces the stable circulating levels that make T4 the preferred replacement hormone. A dose change requires 4-6 weeks (five half-lives) to reach new steady state, which is why TSH should not be re-measured earlier than six weeks after a dose adjustment.
Food, calcium, iron, aluminum-containing antacids, bile acid sequestrants, and soy proteins reduce absorption significantly - hence the 30-60 minute empty-stomach dosing convention. Peripheral T4-to-T3 conversion is reduced by glucocorticoids, propranolol at high doses, amiodarone, and certain illnesses (for example severe systemic illness, 'low T3 syndrome').
What to expect
First 1-2 weeks: minimal perceptible change. Plasma T4 is climbing toward new steady state but peripheral T3 levels lag.
Weeks 3-6: clinical improvement in fatigue, cold intolerance, constipation, dry skin, and mood. TSH begins to drop. Recheck TSH at week 6 and adjust dose accordingly.
Months 2-4: full steady state and symptomatic benefit. Subsequent dose changes take another 6 weeks to equilibrate. Maintenance dosing is typically lifelong in primary hypothyroidism.
Evidence
Interactions & stacking
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Side effects & safety
Commonly reported
- Typically no side effects at correct replacement dose - T4 replaces a deficient hormone
- Symptoms of overdose: tachycardia, palpitations, tremor, heat intolerance, insomnia, weight loss, diarrhea
- Symptoms of underdose: fatigue, cold intolerance, constipation, dry skin, weight gain, brain fog
- Transient hair shedding early in therapy is common and self-limiting
Less common & notes
- Chronic over-replacement increases the risk of atrial fibrillation (especially in older patients) and accelerates bone turnover (osteoporosis risk).
- Rare allergic reactions to tablet excipients (dyes, lactose) - hypoallergenic formulations like Tirosint are available.
- Angina or myocardial ischemia can be precipitated by starting too high a dose in patients with underlying coronary disease - hence the lower 25 mcg starting dose in cardiac patients.
- Pregnancy dose requirement increases ~30% - requires close TSH monitoring.
Pharmacokinetics
Storage. Store at controlled room temperature (20-25°C / 68-77°F). Protect from light and moisture. Keep in original container. Shelf life typically 2-3 years from manufacture date. Moisture can degrade potency - do not transfer to humid pill organizers long-term. Keep out of reach of children.
Regulatory status
FDA-approved under brand names including Synthroid (AbbVie), Levoxyl (Pfizer), Tirosint (IBSA), Euthyrox (Merck KGaA), and Unithroid (Jerome Stevens). Generic levothyroxine is widely available. Prescription-only in the United States; not a controlled substance. Not prohibited by WADA - thyroid hormones are not on the current WADA prohibited list, though monitored in athletes. Internationally available under various brand names.
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