Thioureylenes

The thioureylene drugs inhibit thyroid hormone synthesis by inhibiting thyroid peroxidase, an essential enzyme for thyroid hormone synthesis (see Web Figure 20-1). Thioureylenes do not influence iodide trapping by thyroidal follicular cells or release of preformed T₄ and T₃. Methimazole is the antithyroid drug licensed in North America, while carbimazole, a prodrug of methimazole, is available in Europe. The usual starting dose for methimazole is 2.5 mg per cat q8-12h PO and most cats respond clinically within 2 to 3 weeks of starting therapy. The maintenance dose should be titrated to maintain the TT₄ within the reference range in general, and the lower half if possible; it is important to avoid both iatrogenic hypothyroidism, which is associated with shorter survival in azotemic cats, and mild hyperthyroidism (Williams, 2010). The final dose required for maintenance of euthyroidism ranges from 2.5 to 20 mg of methimazole per day. The most common adverse effects observed in up to 20% of cats include anorexia, vomiting, and lethargy. Transdermal administration of methimazole is associated with a lower risk of gastrointestinal side effects (Sartor et al, 2004). Other adverse effects include mild hematologic abnormalities such as leukopenia, lymphocytosis, and eosinophilia; less commonly severe neutropenia, thrombocytopenia, anemia, facial pruritus, toxic hepatopathy, and bleeding diatheses may occur, which should prompt immediate discontinuation of the drug. Most adverse effects occur within the first 3 months of treatment; thus cats treated with methimazole should have a CBC, platelet count, biochemical profile, and TT₄ concentration evaluated every 2 weeks for the first 3 months of therapy.

The advantages of antithyroid drugs include low daily cost and rapid reversibility of the antithyroid effect. Disadvantages include the need to administer medications at least twice daily in most cats, risk of adverse effects, failure to respond in some patients, problems with owner compliance with administration of medication, and control rather than cure of disease. Methimazole is recommended for cats with concurrent medical problems that preclude definitive treatment, when financial limitations prevent more expensive treatment options, and in patients with suspected underlying renal dysfunction because resolution of the hyperthyroid state may unmask underlying renal disease. If indicators of renal function remain stable during treatment with methimazole, it is more likely that definitive therapy will be well tolerated. If clinical signs of renal failure develop or there is a clinically significant worsening of azotemia after establishing euthyroidism (e.g., > 25% increase in blood urea nitrogen [BUN] or creatinine or development of clinical signs of azotemia), definitive therapy with ¹³¹iodine or thyroidectomy should be avoided and consideration should be given to long-term medical management.