## Why Propylthiouracil (PTU) is right PTU is the drug of choice in the first trimester of pregnancy because it inhibits thyroid peroxidase (TPO) — the enzyme marked **B** — blocking all three catalytic steps: iodide oxidation, organification (iodination of tyrosine residues to form MIT and DIT), and coupling (MIT + DIT → T3; DIT + DIT → T4). Critically, PTU also inhibits peripheral 5'-deiodinase, reducing conversion of T4 to T3 in peripheral tissues. Methimazole is teratogenic (associated with aplasia cutis and methimazole embryopathy) and is contraindicated in the first trimester. PTU is therefore the standard of care for thyrotoxicosis in early pregnancy (Harrison 21e Ch 384; KD Tripathi 9e Ch 19). ## Why each distractor is wrong - **Methimazole**: Although it does inhibit TPO and block all three enzymatic steps, it is teratogenic in the first trimester and causes aplasia cutis and congenital anomalies. It is reserved for the 2nd and 3rd trimesters when the risk of organogenesis is lower. - **Carbimazole**: While carbimazole is a prodrug converted to methimazole and does inhibit TPO, it carries the same teratogenic risk as methimazole in early pregnancy and is not preferred in the first trimester. - **Iodine solution (Lugol's)**: Although iodine inhibits TPO and reduces thyroid hormone release acutely, it is not suitable for long-term management in pregnancy. It can cross the placenta and cause fetal hypothyroidism and goiter, and its effect is transient (escape phenomenon). It is reserved for thyroid storm preparation, not chronic first-trimester management. **High-Yield:** PTU in 1st trimester (teratogenicity of methimazole); methimazole in 2nd/3rd trimester (hepatotoxicity of PTU); PTU also blocks peripheral T4→T3 conversion (advantage in thyroid storm). [cite: Harrison 21e Ch 384; KD Tripathi 9e Ch 19]
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