Antithyroid Medicine Prescribing

Antithyroid drugs (thionamides) block thyroid hormone synthesis and are used in Graves disease, toxic nodular goitre and before definitive therapy. Carbimazole (converted to methimazole) and methimazole are first line; propylthiouracil is reserved for the first trimester of pregnancy, thyroid storm and intolerance of the other drugs, because of liver toxicity. Treatment of Graves disease usually lasts 12 to 18 months, and about half relapse.

Onset. Clinical effect takes 2 to 6 weeks, since stored hormone must be used up. Beta blockers give early symptom control.

Biochemical monitoring. TSH stays suppressed for months, so dose changes are set by free T4 (and free T3).

First line. Carbimazole or methimazole.

Propylthiouracil. First trimester of pregnancy, thyroid storm, and reactions to carbimazole.

Symptom control. Propranolol or another beta blocker; use verapamil or diltiazem if beta blockers are contraindicated.

Definitive therapy. Radioiodine or thyroidectomy for relapse, large goitre, severe eye disease considerations, and patient preference.

Contraindications. Prior agranulocytosis or severe reaction to a thionamide, and propylthiouracil in liver disease.

Carbimazole titration regimen. 20 to 40 mg orally once daily until euthyroid (usually 4 to 8 weeks), then reduce stepwise to a maintenance dose of 5 to 15 mg once daily for 12 to 18 months. Methimazole doses are two thirds of the carbimazole dose (carbimazole 10 mg is about methimazole 6 mg).

Block and replace. Carbimazole 40 mg orally once daily plus levothyroxine 50 to 150 micrograms daily for 6 months; fewer dose changes but more adverse effects.

Propylthiouracil. 100 mg orally three times daily, reduced to 50 mg two or three times daily; usual maximum 300 mg daily (up to 600 mg in severe disease).

Beta blocker. Propranolol 10 to 40 mg orally three to four times daily, up to 160 mg daily, until the hormones are controlled.

Thyroid storm.

• Propylthiouracil 500 to 1000 mg orally or by tube as a load, then 250 mg every 4 hours; or methimazole 20 mg every 4 to 6 hours.
• Propranolol 60 to 80 mg orally every 4 hours, or 1 mg intravenously slowly with monitoring; esmolol when intravenous control is needed.
• Hydrocortisone 100 mg intravenously every 8 hours.
• Potassium iodide or Lugol solution (about 5 drops, or 250 mg every 6 hours) at least 1 hour after the first thionamide dose.
• Cholestyramine 4 g orally every 6 hours if available.
• Treat the precipitant and give cooling and fluids in intensive care.

Pregnancy. Use propylthiouracil in the first trimester (carbimazole and methimazole are linked to embryopathy), then change to carbimazole or methimazole from the second trimester, using the lowest dose to keep free T4 in the upper normal range. Avoid block and replace.

Breastfeeding. Methimazole up to 20 mg daily (carbimazole up to 30 mg) is compatible with infant thyroid checks; propylthiouracil up to 300 mg daily is an alternative.

Special groups. - Liver disease: avoid propylthiouracil; use carbimazole with monitoring. - Kidney impairment: no routine adjustment. - Older adults and cardiac disease: control rate early with a beta blocker and consider early definitive therapy. - Children: weight-based doses by paediatric endocrinology.

Baseline. Full blood count with neutrophils, liver tests, free T4, free T3, TSH, and TSH receptor antibodies.

Monitoring. Free T4 and free T3 every 4 to 6 weeks until stable, then every 2 to 3 months; TSH receptor antibodies near the end of treatment. During pregnancy, free T4 every 2 to 4 weeks. Liver tests every 2 to 4 weeks for the first 3 months of propylthiouracil, and as needed afterwards.

Agranulocytosis. Rare (about 0.2 to 0.5%) and abrupt. Warn every patient to stop the drug and have an urgent blood count for sore throat, mouth ulcers or fever. Stop for neutrophils under 1.0 x 10^9/L.

Stopping. Stop for agranulocytosis, jaundice or liver injury (ALT over 3 times the upper limit of normal with symptoms), severe rash, vasculitis, or pancreatitis. Do not re-challenge after agranulocytosis.

Referral and escalation. Refer to endocrinology for all new Graves disease, pregnancy, thyroid eye disease, thyroid storm, relapse, or any serious reaction. Treat suspected storm as an emergency with admission to intensive care.