Thyroid & Antithyroid
When a vignette puts you on a thyroid drug, the exam is testing dosing, monitoring intervals, and the pregnancy switch. Levothyroxine replaces T4 in hypothyroidism; dose by weight (~1.6 mcg/kg/day in healthy adults, lower in elderly and cardiac patients), take on an empty stomach, separate from calcium, iron, and PPIs by four hours, and recheck TSH at 6–8 weeks after any change. For hyperthyroidism, methimazole is first-line — except in the first trimester of pregnancy, where propylthiouracil (PTU) is preferred to avoid methimazole embryopathy; switch back to methimazole in the second trimester to avoid PTU hepatotoxicity. Both agents carry agranulocytosis warnings — fever and sore throat means stop and check a CBC.
📖 Overview
Levothyroxine is synthetic T4, first-line for all causes of hypothyroidism. Methimazole blocks thyroid hormone synthesis and is first-line for hyperthyroidism (Graves, toxic adenoma). Propylthiouracil (PTU) is preferred only in the 1st trimester of pregnancy (methimazole → aplasia cutis) and in thyroid storm (blocks peripheral T4→T3 conversion).
⚙️ Mechanism of Action
Levothyroxine = T4 replacement. Methimazole / PTU = thioamides — block thyroid peroxidase → ↓ T3/T4 synthesis. PTU additionally inhibits peripheral T4→T3 conversion.
💎 Board Pearls
- 🕐 Levothyroxine: empty stomach, 30–60 min before breakfast, separate from calcium/iron/coffee by 4 hours.
- 📊 Recheck TSH 6–8 weeks after dose change (long half-life).
- 🤰 Pregnancy: levothyroxine needs ↑ ~30%; TSH goal <2.5 in first trimester.
- 🔄 1st trimester = PTU; 2nd/3rd trimester = switch to methimazole (PTU hepatotoxicity).
- 🔥 Thyroid storm: PTU + beta-blocker + iodine + glucocorticoid.
- ⚠️ Methimazole → agranulocytosis (rare) — warn patients about fever/sore throat.
- 💡 Elderly or CAD: start levothyroxine LOW (12.5–25 mcg) and titrate slowly (cardiac stress).
💊 Drugs in This Class
- Levothyroxine — Synthroid, Levoxyl, TirosintHypothyroidism (all causes), thyroid cancer suppression, myxedema coma.
- Methimazole — TapazoleHyperthyroidism (Graves, toxic adenoma), preparation for thyroidectomy or RAI, 2nd-3rd trimester pregnancy.
- Propylthiouracil — PTUHyperthyroidism in 1st-trimester pregnancy, thyroid storm, methimazole intolerance.
Practice Questions
A 29-year-old woman with Graves disease, currently managed on methimazole 10 mg daily, presents at 8 weeks gestation after a positive home pregnancy test. TSH is suppressed, free T4 mildly elevated. She is asymptomatic. Which medication adjustment is MOST appropriate at this visit?
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