**2.2 Propylthiuracil**

Propylthiuracil is an antithyroid drug that is frequently used as a second treatment option in hyperthyroidism after methimazole due to an increased risk of hepatotoxicity, as well as in patients with a contraindication to methimazole or radioactive iodine therapy. Propylthiuracil is preferred as the first line of treatment in patients with thyroid storm because of its greater effect in theory, by inhibiting the peripheral conversion of t4 to t3 by inhibiting thyroid deiodinase. Propylthiuracil is also preferred in the first trimester of pregnancy because of the toxicity of methimazole [20, 21].

The mechanism of action of propylthiuracil is inhibition of thyroid peroxidase, which oxidizes iodine and incorporates it into the tyrosine molecule, preventing the formation of diiodotyrosine and monoiodothyronine. Unlike methimazole, it has a peripheral effect by inhibiting the conversion of T4 to T3 by inhibition of deiodinase [19, 20].

The route of administration is oral. The presentation is tablet of 50 mg. The initial dose depends on the severity with the usual starting dose 300 mg daily divided every 8 hours, with titration of the dose up to a maximum dose of 600 to 900 mg daily. The usual maintenance dose is 100 to 150 mg per day. In patients with thyroid storm the usual dose is 500 to 1000 mg daily divided every 4 hours [19–21].

Hepatic injury is one of the most worrisome adverse effects of the use of propylthiuracil, it occurs frequently in the first 6 months of treatment, however it can occur at any time, the symptoms are specific and the initial diagnosis is made by elevation of liver function markers. Due to the high risk of hepatotoxicity in pregnancy, methimazole is preferred in the second and third trimester of pregnancy [19–21].

Less frequently, propylthiuracil has been associated with ANCA-associated vasculitis that can cause glomerulonephritis, alveolar hemorrhage, central nervous system compromise, and leukocytoclastic vasculitis, may improve with drug withdrawal or require additional immunosuppressive treatment [19–21].

Agranulocytosis can occur in up to 0.5% of patients, especially in the first 3 months of treatment, the symptoms as in methimazole agranulocytosis are sore throat and fever and the patient should be advised of attend the emergency department in case of presenting these symptoms. Other adverse effects are hypersensitivity, hypothyroidism, and potential teratogenicity. Less frequently, multiple adverse effects have been described, including dermatological manifestations, interstitial nephritis, neuritis, paresthesia, headache, vertigo, lymphadenopathy, splenomegaly, aplastic anemia, fever, and lupus-like [19–21].
