Thyroid and Antithyroid Drugs
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Direct answer
Hypothyroidism is treated with levothyroxine (T4) 1.5–1.6 microgram/kg daily on an empty stomach, 30–60 minutes before breakfast, with the dose increased by about 30 per cent in pregnancy. Hyperthyroidism is controlled by thionamides — carbimazole or methimazole once daily, or propylthiouracil which additionally blocks peripheral T4-to-T3 conversion: propylthiouracil in the first trimester (methimazole embryopathy), switching to carbimazole later because propylthiouracil causes fulminant hepatitis. Thyroid storm combines propylthiouracil, iodine (given an hour after the thionamide), propranolol and hydrocortisone; radioactive iodine I-131 suits definitive Graves therapy outside pregnancy.
What you must remember
- Levothyroxine has a half-life of seven days — steady state takes six weeks, so dose changes are assessed at that interval with TSH.
- Absorption is spoiled by food, calcium, iron, proton pump inhibitors and soy — the empty-stomach rule and drug-spacing counselling are examinable.
- Start at 25 microgram in the elderly or those with cardiac disease, titrating slowly; overtreatment provokes angina and atrial fibrillation.
- Pregnancy raises levothyroxine requirements about 30 per cent from the first trimester; untreated maternal hypothyroidism impairs fetal neurodevelopment, and TSH is checked each trimester.
- Agranulocytosis is the dangerous thionamide toxicity — any sore throat or fever on treatment demands an immediate blood count; it is dose-related with methimazole, idiosyncratic with propylthiouracil.
- Methimazole (and its prodrug carbimazole) embryopathy: aplasia cutis and choanal atresia — propylthiouracil is the first-trimester drug.
- Propylthiouracil carries a black-box warning for fulminant hepatic necrosis — the reason it yields to carbimazole after the first trimester.
- Thyroid storm sequence: propylthiouracil first, then Lugol's iodine or saturated potassium iodide one hour later (iodine given first would fuel new hormone synthesis), propranolol, hydrocortisone, cooling and treating the trigger.
- Radioactive iodine I-131 is contraindicated in pregnancy and breastfeeding; it can transiently worsen ophthalmopathy, so smokers and active eye disease are treated with caution.
- Beta-blockers (propranolol) control adrenergic symptoms in the first weeks before thionamides work.
How to work through a pregnant thyrotoxic patient
A 26-year-old at eight weeks with Graves disease, pulse 110, free T4 high, TSH suppressed. The reasoning runs trimester by trimester. First, confirm it is Graves and not gestational transient thyrotoxicosis (no eye signs, no thyroid-stimulating antibody, severe vomiting history favour the latter, which needs no thionamide). Second, choose propylthiouracil in the first trimester — the lowest dose controlling symptoms, because methimazole's aplasia cutis and choanal atresia risk is confined to weeks 6–10 of organogenesis. Third, plan the switch to carbimazole after the first trimester to protect the liver from propylthiouracil. Fourth, monitor free T4 (not TSH, which stays suppressed) every four weeks, keeping free T4 at the upper normal range for pregnancy — overtreatment causes fetal hypothyroidism and goitre, since both drugs cross the placenta. Fifth, expect the disease to ameliorate in the second half of pregnancy and anticipate postpartum flare. Sixth, breastfeeding is safe with low-dose thionamides (propylthiouracil preferred classically after feed). The case compresses every thionamide decision the exam asks.
Where students slip
The classic wrong answer is ordering iodine before the thionamide in thyroid storm — iodine given first becomes substrate for new hormone; one hour after propylthiouracil, it blocks release. The second slip is monitoring TSH instead of free T4 in pregnancy or early treatment, when TSH lags months behind. Third, forgetting levothyroxine's six-week steady state produces answers adjusting doses weekly. Fourth, the sore throat question: a patient on carbimazole with fever and throat ulceration needs an urgent white cell count, not antibiotics — agranulocytosis kills and both drug and answer must stop. Finally, calcium and iron tablets taken with levothyroxine appear repeatedly as a pharmacokinetics interaction stem.
Frequently asked questions
Why is propylthiouracil chosen in the first trimester of pregnancy?
Methimazole and carbimazole cause a specific embryopathy (aplasia cutis, choanal atresia) during organogenesis; propylthiouracil, despite its liver risk, is the safer first-trimester thionamide.
How is thyroid storm managed and in what order?
Propylthiouracil load, then iodine one hour later to block hormone release, propranolol for adrenergic control, hydrocortisone (blocks conversion and treats relative adrenal insufficiency), cooling, and treatment of the precipitant.
What counselling follows a levothyroxine prescription?
Take on an empty stomach 30–60 minutes before breakfast, separate calcium, iron and soy by four hours, allow six weeks between dose changes, and report angina or palpitations early in the elderly.
How does radioactive iodine fit Graves management?
It is definitive outpatient therapy for adults not planning pregnancy, contraindicated in pregnancy and breastfeeding, with a small risk of worsening ophthalmopathy — steroid cover is considered for active eye disease.
What is the warning sign of thionamide agranulocytosis?
Sore throat, fever or mouth ulceration demands an immediate differential count; if neutrophils are low, stop the drug, give broad-spectrum antibiotics and never rechallenge with either thionamide.