SN4 SHORT NOTE 5M ★ High-yield

Describe the antithyroid drugs with their mechanisms, adverse effects and treatment strategies.

Pharmacology · 2nd Professional — Para-Clinical

Drugs and Mechanisms

Drug	Mechanism	Key features
Carbimazole	A prodrug converted to methimazole; inhibits thyroid peroxidase, blocking iodination of tyrosine and the coupling reaction	First-line in most situations; once-daily dosing; more potent than propylthiouracil
Propylthiouracil (PTU)	Same enzyme, plus inhibition of peripheral conversion of T4 to T3 by deiodinase	Preferred in thyroid storm (the extra action) and in the first trimester (carbimazole is teratogenic); but causes severe hepatotoxicity, so it is not first-line otherwise
Beta-blockers — propranolol	Block sympathetic effects; high doses also reduce peripheral conversion	Act within hours, whereas thionamides take 2–6 weeks because stored hormone must first be used up — so they cover the interval
Iodides (Lugol solution)	Inhibit hormone release and reduce vascularity	Short-term only — preoperative preparation and thyroid storm; the effect escapes in about 2 weeks
Radioiodine (I-131)	Beta radiation destroys follicular cells	Definitive, cheap and simple; contraindicated in pregnancy and lactation; hypothyroidism is expected and accepted

CLINICAL PEARL

Antithyroid drugs block synthesis but not release, which is why nothing happens for weeks. The gland holds enough stored colloid for several weeks of hormone output, so a thionamide cannot help the patient’s tremor and tachycardia today. A beta-blocker works within hours by treating the symptoms directly. The two are therefore started together, and the beta-blocker withdrawn as the thionamide takes effect.

Adverse Effects

Agranulocytosis — the effect that matters: idiosyncratic, sudden, in about 0.3%, most often in the first 3 months and at higher doses. Every patient must be instructed to stop the drug and obtain an urgent full blood count if they develop a sore throat, fever, or mouth ulcers. Routine monitoring does not reliably predict it because the onset is abrupt
Common minor effects — rash, urticaria, pruritus, arthralgia, gastrointestinal upset, altered taste; often manageable by switching agents
Propylthiouracil — hepatotoxicity including fulminant hepatic failure requiring transplantation; the reason it lost its first-line status
Carbimazole — cholestatic jaundice
ANCA-associated vasculitis, chiefly with propylthiouracil
Teratogenicity of carbimazole — aplasia cutis of the scalp, choanal and oesophageal atresia, and dysmorphic features
Hypothyroidism from overtreatment — avoided by titrating the dose against free T4

Treatment Strategies

Approach	Details
Titration regimen	Start high, reduce to the lowest dose maintaining euthyroidism; fewer adverse effects; usually 12–18 months, after which about half remain in remission
Block and replace	A full blocking dose of carbimazole with levothyroxine added; fewer monitoring visits and more stable, but a higher total drug exposure and more adverse effects
Radioiodine	Definitive; used after relapse, in older patients and in nodular disease; may transiently worsen thyroid eye disease, so steroid cover is given in those at risk
Surgery	Large goitre, compression, suspicion of malignancy, pregnancy where drugs fail, or patient preference; requires preoperative euthyroidism and Lugol iodine

Applied Aspects

Give the agranulocytosis warning in writing at the first prescription, and repeat it; this is the single most important safety instruction in the topic
Do not treat a sore throat in a patient on carbimazole with an antibiotic without a blood count — that is precisely how fatal agranulocytosis is missed
Monitor free T4 rather than TSH in the early months, since TSH remains suppressed for weeks after the patient has become euthyroid and will mislead
Use propylthiouracil in the first trimester and switch to carbimazole thereafter, balancing teratogenicity against hepatotoxicity; the lowest dose that keeps free T4 at the upper normal limit is used, since the fetus is more sensitive than the mother
Exclude pregnancy before radioiodine and advise avoiding conception for several months afterwards
Warn about the delay in response, or patients conclude the treatment is not working and stop; the beta-blocker covering that interval should be explained as temporary

All questions in Endocrine Pharmacology

Every Pharmacology chapter →