Progress in the diagnosis and management of feline hyperthyroidism (Proceedings)

Feline hyperthyroidism is the most common endocrine disorder of older cats. Thyroid hormone excess effects multiple organ systems and the associated clinical signs range in severity from mild to severe and are quite variable from cat to cat. As a result of the increased incidence of the disease, the increased index of suspicion among practicing veterinarians and the increased screening of geriatric cats for hyperthyroidism, the average hyperthyroid cat is now evaluated earlier in the course of disease than when the disorder was first recognized. These cats often have relatively mild hyperthyroidism, lack some to many of the classical signs of hyperthyroidism and present a diagnostic challenge for the clinician. Given the prevalence of the disease it is recommended that a T4 level be included in the annual geriatric screening for all cats 8 years of age and older. Thyroid screening can also be recommended for cats 4 years of age and older that are hyperactive, are polyuric and polydipsic, have lost weight, have a heart murmur, tachycardia or gallop rhythm, have an enlarged thyroid on palpation, and in those with an elevation in liver enzyme levels. In most cases the diagnosis of feline hyperthyroidism is straightforward and can be confirmed by demonstrating an elevated serum T4 level. Determination of T3 levels does not add substantial information and is not necessary. Some cases, particularly early hyperthyroidism, can be challenging and require additional testing (thyroid function as well as CBC and chemistry profile, for example). In cats with mild or occult hyperthyroidism, T4 levels can fluctuate into and out of the normal range. Furthermore, concurrent moderate to severe NTI can lower an increased T4 into the normal range. Therefore, a normal T4 does not necessarily exclude hyperthyroidism in a cat with compatible clinical findings. What is recommended in these cases? If NTI is present, the T4 is repeated after the condition has improved or resolved. If NTI is absent, additional testing for hyperthyroidism can be performed. Finally, if NTI is absent, one or more T4 levels can be repeated over the next few weeks. If this fails and hyperthyroidism is still suspected, additional testing is indicated.

Tests to diagnose occult or early hyperthyroidism include determination of fT4 by dialysis, TRH response testing and the T3 suppression test. The dialysis methodology for determining fT4 is preferred over the RIA. Issues with availability of fT4 by dialysis have led to the evaluation of other fT4 assays. Determination of fT4 is readily available at most veterinary diagnostic laboratories and is generally considered the diagnostic test of choice in cats with occult or early hyperthyroidism in which a screening total T4 level was inconclusive. Free T4 levels are usually elevated in cats with occult hyperthyroidism. NTI can occasionally elevate fT4 and must be excluded beforehand. However, in most cats with NTI the accompanying total T4 is low-normal or low. The TRH response test is performed by determining T4 levels before and 6 hours after intravenous administration of TRH. Lack of increase in T4 levels is indicative of hyperthyroidism. The T3 suppression test is performed by determining T4 (and T3 as well) levels before and after administering 25 ug of T3 per os three times daily for 7 doses. Lack of suppression of T4 levels is indicative of hyperthyroidism.

The treatment options for feline hyperthyroidism include long-term antithyroid drug administration, surgical thyroidectomy and radioactive iodine therapy (131I), with each of these treatment options having advantages as well as disadvantages. Several factors must be taken into consideration in order to determine the best treatment option for an individual hyperthyroid patient. These include the age of the cat, concurrent medical problems (e.g., cardiovascular disease or renal disease), availability of each therapy, economic factors and the client's opinions regarding each form of therapy. Regardless of the treatment chosen, regularly scheduled follow-up care including monitoring T4 levels is very important in assuring the best possible therapeutic outcome. The advent of in-house T4 testing can offer a convenient alternative for determination of T4 levels during long-term therapy. In addition, the potential interaction of chronic renal disease (which may initially be subclinical) and hyperthyroidism must be taken into account as both disorders can be seen in the geriatric feline patient. The unmasking of renal disease or the negative impact on renal function resulting from the treatment of hyperthyroidism can influence the type of therapy chosen or necessitate alterations in therapy. Blood pressures should also be monitored before and during therapy.

Several treatment options exist for feline hyperthyroidism. The most commonly used antithyroid drug in the U.S. is methimazole. The starting dosage of the antithyroid drug for an individual cat is typically based on the total T4 level and the weight of the patient. During therapy, a T4 level, CBC, platelet count and chemistry profile are evaluated every 2 to 3 weeks during the initial 3 months of treatment to monitor for any needed dosage adjustments and for the occurrence of adverse effects (thrombocytopenia, anemia, agranulocytosis, hepatopathy). After this a T4 is determined at 6 months of therapy and every 6 months thereafter. The methimazole dosage is adjusted to the lowest effective dose (5 to 10 mg/day in most cats). In cats treated for long periods of time the dose required to maintain control of the hyperthyroid state may increase. Transdermal methimazole can be used if a client is unable to administer oral methimazole. Reported efficacy is lower than oral methimazole, but it is effective in lowering T4 levels over time in most hyperthyroid cats. While fewer GI side effects (4%) are reported compared to oral methimazole (24%), there is no difference in the incidence of drug eruption, blood dyscrasias or hepatotoxicity. Potential disadvantages include increased expense, local skin irritation and issues with stability of the formulation. Treatment options are limited for hyperthyroid cats that do not tolerate methimazole and that are not candidates for radioiodine or surgery. A recent study evaluated iopanoic acid, a cholecystographic agent in an experiment model of feline hyperthyroidism. Treatment of feline hyperthyroidism can unmask chronic renal failure as a result of decreased GFR and RBF associated with the establishment of euthyroidism. A recent study demonstrated that the appearance of mild stable renal azotemia following treatment for hyperthyroidism did not negatively impact survival time as compared to cats that remained nonazotemic. In cats that develop mild stable CRF after treatment for hyperthyroidism, it may not be necessary to withdraw treatment for hyperthyroidism in order to normalize serum creatinine concentrations. Nonetheless, the T4 levels should be regularly checked to avoid over-treatment of hyperthyroidism. Hyperthyroidism is usually listed as a common cause of elevated blood pressure in cats. Two recent studies, however, indicated that hypertension was less common (19% and 9%, respectively) than previously proposed. In addition, it has recently been reported that some cats develop hypertension following therapy for hyperthyroidism (approximately 20%). Whether this relates to the decline in renal function seen when euthyroidism is established is unknown at this time. Therefore, blood pressure should be monitored both before and during therapy in hyperthyroid cats. In people, a syndrome of subclinical hyperthyroidism has been shown to be present and is associated with normal thyroid hormone concentrations and low serum TSH levels. A recent study identified some euthyroid cats with undetectable serum TSH levels. Histopathological examination of the thyroid glands of these cats revealed adenomatous hyperplastic changes intermediate between normal cats and cats with overt hyperthyroidism. The data suggest that a subclinical hyperthyroidism appears to occur in the cat, and measurement of serum TSH may predict the development of hyperthyroidism.

Prior to thyroidectomy, methimazole is administered for 2 to 3 weeks to establish a euthyroid state. A T4, CBC and profile is then checked before surgery. Following surgery the T4 level should be determined before discharge to assure that hyperthyroidism is no longer present. After unilateral thyroidectomy thyroid replacement is rarely given and T4 levels usually normalize in 2 to 4 months (therefore, T4 can be determined at 2 month intervals until normal). Daily thyroxine supplementation is indicated after bilateral thyroidectomy. Thyroid hormone production usually normalizes, however, weeks to months after surgery and replacement therapy can be discontinued. This is monitored by periodic T4 determinations. The most serious postoperative complication that can occur following bilateral thyroidectomy is hypocalcemia secondary to iatrogenic hypoparathyroidism (usually 1 to 4 days postop). Following bilateral thyroidectomy, daily serum calcium levels should be measured until calcium stabilizes in the normal range. During long-term follow-up after thyroidectomy, T4 levels should be determined every 6 months to monitor for recurrence of hyperthyroidism.

Radioactive iodine is a safe and effective treatment alternative for feline hyperthyroidism, and can be considered the treatment of choice in cats with uncomplicated hyperthyroidism. A single treatment is effective in 90 to 95 % of cats and the 5 to 10% that remain hyperthyroid can successfully be retreated in most instances. Hypothyroidism is uncommon. After administration of radioactive iodine, a T4 level should be measured at the time of discharge from the treatment facility and at 2 to 3 months posttreatment. During long-term follow-up a T4 level is determined at 6 months posttreatment and every 6 months thereafter.