Chapter 19: Medical Treatment of Feline Hyperthyroidism

Medical Treatment of Feline Hyperthyroidism *

Lauren A. Trepanier, Madison, Wisconsin

Hyperthyroidism is the most common endocrine disorder in cats, affecting approximately 2% of all cats presenting to veterinary teaching hospitals. Management options include radioiodine therapy, thyroidectomy, and medical treatment with antithyroid drugs such as methimazole. More recently diet has also been advocated in select cases (see Web Chapter 20). Radioiodine is considered the treatment of choice for hyperthyroidism based on its high efficacy and relative lack of complications (Web Table 19-1). However, in some situations methimazole therapy may be preferred over radioiodine. Methimazole is useful before thyroidectomy to normalize serum thyroxine (T₄) concentrations and reduce the risk of tachyarrhythmias during anesthesia. Methimazole, which is reversible, is similarly indicated in cats with renal insufficiency, either for long-term therapy or as a “clinical test” to determine whether serum T₄ can be safely lowered without causing renal decompensation. Practical considerations such as lack of a convenient referral center with a radiation license, client fears about radiation or quarantine, or initial cost to the client may also drive the use of methimazole.

WEB TABLE 19-1

Advantages and Disadvantages of Major Therapies for Feline Hyperthyroidism

Methimazole Actions, Dosing, and Efficacy

Methimazole blocks thyroid hormone synthesis by inhibiting thyroid peroxidase, the enzyme involved in the oxidation of iodide to iodine, incorporation of iodine into thyroglobulin, and coupling of tyrosine residues to form T₄ and triiodothyronine (T₃). Methimazole does not block the release of preformed thyroid hormone, which explains the delay of 2 to 4 weeks before serum T₄ concentrations fully normalize after beginning treatment in cats. Methimazole does not decrease goiter size; in fact, goiters may become larger over time despite therapy.

Typical starting doses of methimazole range from 1.25 to 2.5 mg per cat twice daily (Web Table 19-2). More frequent dosing (three times daily) is rarely necessary. Higher doses of 5 mg two to three times daily, used in original cases of cats with relatively high serum T₄ concentrations, are probably not needed for initial therapy of cats with mild-to-moderate hyperthyroidism and could potentially increase the risk of renal decompensation from a rapid fall in serum T₄. Starting dosages can be titrated upward if there is an inadequate initial response to lower doses of methimazole over 2 to 4 weeks. In cats that tolerate methimazole without side effects, efficacy is greater than 90%.

WEB TABLE 19-2

Drugs Useful in the Medical Management of Hyperthyroidism

GI, Gastrointestinal; T₃, triiodothyronine; T₄, thyroxine; AV, atrioventricular.

In humans, methimazole has a long residence time in the thyroid gland and can exert antithyroid effects for 24 hours or more; therefore methimazole can be given once daily in humans with remission rates that are comparable to divided daily dosing. However, when our group studied 40 hyperthyroid cats we found that once-daily dosing (5 mg) was less effective than divided dosing (2.5 mg twice daily), with only 54% of cats achieving a euthyroid state after 2 weeks of once-daily treatment compared with 87% of cats treated with divided dosing (Trepanier et al, 2003). Therefore, unless clients are unable to dose more frequently than once daily, divided twice-daily dosing of methimazole may be preferred to maximize efficacy. Dosing less frequently than once daily is unlikely to be effective because serum T₄ concentrations rise to pretreatment hyperthyroid values within 48 hours after discontinuing methimazole.

Methimazole Side Effects

Blood Dyscrasias

Methimazole can lead to neutropenia and/or thrombocytopenia in 3% to 9% of treated cats. Cats with methimazole-induced blood dyscrasias usually recover within a week of drug discontinuation. Continuing methimazole in the face of thrombocytopenia has led to clinically significant hemorrhage, including epistaxis and oral bleeding. Rechallenge with methimazole in cats with neutropenia can lead to a recurrent severe neutropenia within 1 week. Although the mechanisms for these blood dyscrasias in cats have not been established, methimazole-induced neutropenia in humans is associated with an arrest of myeloid progenitors in the bone marrow. Treatment with granulocyte-macrophage colony-stimulating factor has been advocated in human patients but does not appear to hasten recovery in most humans.

Facial Excoriation

Approximately 2% to 3% of cats treated with methimazole develop excoriations of the face and neck, leading to characteristic scabbed lesions in front of the pinnae. Generalized erythema and pruritus may also occur. These excoriations are only partially responsive to glucocorticoids, and drug discontinuation is almost always required. Pruritus has also been reported in humans treated with methimazole, but the mechanisms for these reactions have not been explored.

Hepatotoxicity

Increases in serum alkaline phosphatase (SAP) and bilirubin, or alanine aminotransferase (ALT), are observed in approximately 2% of cats treated with methimazole (Peterson, Kintzer, and Hurvitz, 1988); liver biopsy may show hepatic necrosis and degeneration. Liver enzyme elevations are usually reversible over several weeks following drug discontinuation, although nutritional and fluid support may be required. Rechallenge can lead to recurrent hepatopathy, and future drug avoidance is generally recommended. In rodent models methimazole hepatotoxicity is exacerbated by glutathione depletion (Mizutani et al, 1999). The role of glutathione depletion, or supplementation, in methimazole-associated hepatotoxicity in cats has not been evaluated.

Simple Gastrointestinal Upset

Anorexia, vomiting, and lethargy are seen in approximately 10% of cats treated with methimazole. Simple gastrointestinal (GI) upset is most common in the first 4 weeks of treatment and can resolve with a dosage reduction. These signs may be caused in part by direct gastric irritation from the drug, since transdermal administration of methimazole is associated with significantly fewer GI side effects than the oral route (Sartor et al, 2004).

Renal Decompensation

Cats with hyperthyroidism have abnormally high glomerular filtration rates (GFRs), and treating hyperthyroidism by any method leads to decreases in GFR in most hyperthyroid cats. New-onset azotemia is observed in 15% to 20% of hyperthyroid cats after normalization of serum T₄. Although these biochemical changes are generally clinically silent, occasionally cats develop signs of illness referable to underlying renal disease. Because methimazole treatment is reversible, it is the preferred approach for initial treatment of hyperthyroid cats with preexisting azotemia to determine whether normalization of serum T₄ will lead to unacceptable renal decompensation.

Coagulation Abnormalities

Methimazole and to a lesser extent propylthiouracil (PTU) inhibit vitamin K–dependent clotting factor activation (γ-carboxylation) and epoxide reductase (necessary for vitamin K recycling, and the same enzyme targeted by warfarin) at high concentrations. In a study of 20 hyperthyroid cats treated with methimazole, there were no significant changes in prothrombin time or activated partial thromboplastin time, but one cat developed a prolonged protein-induced by vitamin K antagonism (PIVKA) clotting time (Randolph et al, 2000). No cats had clinically significant bleeding. This suggests a possible but apparently uncommon “warfarin-like” effect of methimazole in cats. This reaction is rare enough not to warrant routine monitoring but should be considered in any cat presenting with hemorrhage that is also being treated with methimazole.

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Jul 18, 2016 | Posted by admin in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off

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