A 38-year-old woman presents with fatigue, weight gain, and cold intolerance for 3 months. Laboratory investigations show TSH 8.2 mIU/L (normal 0.4–4.0) and free T4 0.8 ng/dL (normal 0.8–1.8). She has no history of iodine deficiency or autoimmune disease. What is the drug of choice for her hypothyroidism?

Explanation

## First-Line Treatment of Primary Hypothyroidism **Key Point:** Levothyroxine (synthetic T4) is the gold standard and first-line agent for all forms of primary hypothyroidism, including autoimmune thyroiditis, iodine deficiency, and post-thyroidectomy hypothyroidism. ### Why Levothyroxine? 1. **Stable, predictable pharmacokinetics** - Long half-life (~7 days) allows once-daily dosing - Steady-state achieved in 4–6 weeks - Minimal fluctuations in serum T4 and T3 levels 2. **Peripheral conversion to T3** - T4 is converted peripherally to active T3 by deiodinase enzymes - Maintains physiologic T3/T4 ratio - Allows tissue-specific regulation of thyroid hormone action 3. **Ease of titration** - Dose adjusted based on TSH response - Initial dose: 25–50 mcg daily; increase by 25–50 mcg every 4–6 weeks - Target TSH: 0.5–2.5 mIU/L in most patients 4. **Cost-effectiveness and availability** - Inexpensive and widely available - Multiple formulations (tablet, liquid, IV) **High-Yield:** Levothyroxine is absorbed best on an empty stomach (30–60 min before food). Absorption is reduced by iron, calcium, and PPIs—separate dosing by ≥4 hours. **Clinical Pearl:** In this patient with primary hypothyroidism (elevated TSH, low-normal T4), levothyroxine monotherapy is sufficient. Combined T4/T3 therapy is reserved for select cases (post-thyroidectomy, central hypothyroidism, or persistent symptoms despite adequate TSH suppression). ### Dosing in This Case - Initial dose: 50 mcg daily - Recheck TSH in 6 weeks - Titrate to achieve TSH 0.5–2.5 mIU/L [cite:Harrison 21e Ch 397]