Antithyroid Drugs

Antithyroid drugs reduce thyroid hormone production or effect. The core agents are the thionamides, with iodine, lithium, potassium perchlorate, cholestyramine, glucocorticoids and beta blockers used as adjuncts. They treat Graves disease, toxic nodular disease, thyroid storm, and prepare patients for radioiodine or surgery.

Mechanism. Thionamides inhibit thyroid peroxidase. Iodine in pharmacological doses transiently blocks hormone release and synthesis (Wolff-Chaikoff effect). Glucocorticoids and propranolol reduce peripheral T4 to T3 conversion, and propranolol also controls adrenergic symptoms. Cholestyramine binds thyroid hormone in the gut and interrupts recycling.

Pharmacokinetics. Thionamides concentrate in the thyroid, so single daily dosing of methimazole is effective despite a short plasma half-life. Control takes 4 to 8 weeks because stored hormone must be depleted.

Thionamides. Carbimazole (converted to methimazole), methimazole (thiamazole) and propylthiouracil. The main first-line choice is carbimazole or methimazole; propylthiouracil is reserved for thyroid storm, first-trimester pregnancy and thionamide intolerance.

Adjuncts. Propranolol 40 mg every 6 to 8 hours (to 80 mg) for symptom control, potassium iodide before surgery or in storm, lithium when thionamides cannot be used, and potassium perchlorate in amiodarone-induced thyrotoxicosis in some regions.

Differences. Radioiodine and surgery are definitive options; antithyroid drugs are not curative in toxic nodular disease and induce lasting remission in about 50% with Graves disease.

• Graves disease: thionamide for 12 to 18 months with a titration regimen, or a block and replace regimen with levothyroxine for 6 months; relapse occurs in about half.
• Preparation for radioiodine: stop the thionamide 3 to 7 days before and restart 3 to 7 days after. In older patients or those with cardiac disease, achieve euthyroidism first and keep the break short.
• Preparation for surgery: thionamide until euthyroid, then potassium iodide for 7 to 10 days.
• Thyroid storm: propylthiouracil 500 to 1000 mg loading then 250 mg every 4 hours (or methimazole 60 to 80 mg daily); iodine solution (Lugol 8 drops every 6 to 8 hours) given at least 1 hour after the thionamide; propranolol 60 to 80 mg every 4 hours (or esmolol infusion); hydrocortisone 100 mg intravenously every 8 hours; cholestyramine 4 g every 6 hours; and supportive care with cooling and treatment of the trigger.
• Pregnancy: propylthiouracil in the first trimester, then change to carbimazole or methimazole; keep free T4 at the upper end of the normal range on the lowest dose.

Special groups. Breastfeeding: methimazole up to 20 to 30 mg daily or propylthiouracil up to 300 mg daily is acceptable. Children: methimazole is preferred, propylthiouracil is avoided. Older adults: beta blockers for symptoms and early definitive treatment. Regional: endemic goitre and iodine supplementation can cause iodine-induced hyperthyroidism, and radioiodine access is limited, so long courses of thionamide or surgery are common.

Adverse effects. Rash and itch in about 5%, arthralgia, agranulocytosis (0.2 to 0.5%), liver injury, and with propylthiouracil, ANCA-associated vasculitis. Iodine can cause thyroiditis and thyroid dysfunction. Lithium causes tremor and renal effects.

Counselling. Any sore throat, mouth ulcers or fever means stop the drug and arrange a same-day neutrophil count.

Interactions. Warfarin and digoxin requirements change as the patient becomes euthyroid. Beta blockers are avoided in asthma.

Monitoring. Baseline FBC and liver enzymes, then free T4 and T3 every 4 to 6 weeks (TSH lags), and every 3 to 4 months once stable.

Referral and escalation. Thyroid storm, agranulocytosis, relapse, orbitopathy, pregnancy, or thyroid nodule.