Drugs for hyperthyroidism

Thioamides, such as carbimazole and propylthiouracil, inhibit thyroid peroxidase and interfere with the formation of thyroid hormones. Carbimazole is a prodrug metabolised to the active metabolite thiamazole (also known as methimazole). As there are thyroid hormones stored in the thyroid gland, the onset of clinical action can vary from 3 to 12 weeks. Generally, carbimazole or thiamazole is preferred to propylthiouracil as it has a longer half-life and lower risk of hepatotoxicity. However, propylthiouracil has a faster onset of clinical action as it additionally inhibits the conversion of T4 to the more potent T3 and is therefore preferred for treating thyrotoxic crisis (or thyroid storm). Propylthiouracil is also preferred during the first trimester of pregnancy as it has a lower risk of teratogenicity. A rare (approximately 0.3 to 0.6 %) but potentially severe adverse effect of thioamides is agranulocytosis, which puts patients at risk of opportunistic infections. Therefore periodic blood counts are required, and patients must be warned to report any signs of infection (e.g., sore throat or fever). Fortunately, the agranulocytosis is reversible on thioamide withdrawal.

Iodides at high concentrations activate the Wolff-Chaikoff effect, an autoregulatory phenomenon suppressing thyroid hormone synthesis and the release of thyroid hormones. Formulations include Lugol's solution, consisting of 5 % iodine and 10 % potassium iodide or potassium iodide tablets or saturated solution. Due to the suppression of thyroid hormone release, the onset of clinical action occurs within 24 to 48 hours and achieves a peak effect after 10 to15 days of continuous therapy. Because of the rapid onset of action, iodides are useful in the treatment of thyrotoxic crisis. Iodides can decrease thyroid gland size and vascularity when given over 1 to 2 weeks and so are also helpful before surgical thyroidectomy. However, the effect is not maintained when the iodide is discontinued. As iodide is required for thyroid hormone synthesis, when the gland "escapes" from the iodide block, it may produce severe exacerbations of thyrotoxicosis.  

Radioiodine (¹³¹I) can be used for pharmacological thyroidectomy. Following oral administration, the radioiodine is rapidly concentrated in the thyroid gland, minimising exposure of the rest of the body to the radioactivity. ¹³¹I has a radioactivity half-life of 8 days and emits β particles and γ rays. The destructive β particles do not penetrate far and so destroy the thyroid gland with no detectable damage to surrounding tissues. However, the time course of the cytotoxic effect is slow, and it takes 2 to 3 months for the symptoms of hyperthyroidism to abate.

Drugs used for the management of thyrotoxic crisis include propylthiouracil, iodides, colestyramine, beta-blockers, corticosteroids and paracetamol. Propylthiouracil and iodides are used to suppress thyroid hormone production but are preferred to carbimazole or its active metabolite thiamazole because they have a faster onset of action as they inhibit the conversion of T4 to T3 and, in the case of iodides, the release of thyroid hormones. As thyroid hormones undergo enterohepatic recycling, being released in bile and reabsorbed in the small intestine, the bile-salt binding resin colestyramine can reduce plasma thyroid hormone levels during thyrotoxic crisis. Propranolol is a beta-blocker used to reduce the cardiovascular risk of acute hyperthyroidism. Although it is a nonselective beta-blocker, it is preferred for treating hyperthyroidism as it additionally reduces the conversion of T4 to the more potent T3. Corticosteroids, such as hydrocortisone (cortisol) or dexamethasone, are used to control systemic effects, including the risk of adrenal suppression and fever. Paracetamol is also used as an antipyretic.