## Drug of Choice for Primary Hypothyroidism **Key Point:** Levothyroxine (synthetic T4) is the gold standard and first-line treatment for all forms of primary hypothyroidism. ### Why Levothyroxine? 1. **Peripheral conversion to T3**: Levothyroxine is converted peripherally to T3 by deiodinase enzymes, allowing physiologic regulation of hormone levels. 2. **Long half-life (~7 days)**: Permits once-daily dosing and stable serum levels. 3. **Predictable pharmacokinetics**: Consistent absorption and metabolism allow precise dose titration. 4. **Cost-effective**: Inexpensive and widely available. 5. **Excellent safety profile**: Minimal side effects when dosed appropriately. ### Dosing Strategy - **Initial dose**: 25–50 mcg daily (lower in elderly, cardiac disease). - **Titration**: Increase by 25–50 mcg every 6–8 weeks until TSH normalizes (target 0.5–2.5 mIU/L). - **Maintenance**: Usually 75–150 mcg daily. **High-Yield:** TSH is the most sensitive marker for dose adjustment in primary hypothyroidism. Recheck TSH 6–8 weeks after each dose change. ### Clinical Pearl Absorption is best on an empty stomach; advise the patient to take levothyroxine 30–60 minutes before breakfast. Avoid concurrent calcium, iron, and proton pump inhibitors, which impair absorption. | Feature | Levothyroxine | Liothyronine | Desiccated Extract | Liotrix | | --- | --- | --- | --- | --- | | **Half-life** | ~7 days | ~1.5 days | Variable | ~7 days (T4) | | **Dosing** | Once daily | 2–3 times daily | Variable | Once daily | | **Stability** | Excellent | Poor (fluctuations) | Inconsistent potency | Good | | **Preferred in** | All primary hypothyroidism | Post-thyroidectomy, acute myxedema | Rare (historical) | Not recommended | **Warning:** Liothyronine causes rapid T3 spikes and is reserved for acute myxedema coma or post-thyroidectomy; it is unsuitable for chronic replacement due to fluctuating levels and increased cardiac risk.
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