Feline Hyperthyroidism

Jeff S. Stortz, DVM; Kenneth S. Latimer, DVM, PhD; Heather L. Tarpley, DVM; Bruce E. LeRoy, DVM, PhD, Perry J. Bain, DVM, PhD, T. Michelle Wall, DVM, DACVIM

Class of 2004 (Stortz), Department of Pathology (Latimer, Tarpley, LeRoy, Bain), and Department of Small Animal Medicine (Wall), College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388

Introduction

Hyperthyroidism is a clinical condition caused by excessive production and secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland (Fig. 1). In cats, it is usually caused by an autonomous thyroid condition, but rarely can result from a hypothalamic or pituitary disorder. Thyroid gland hyperplasia and thyroid adenomas (benign tumors of the thyroid gland) are diagnosed much more commonly than malignant tumors (carcinomas). In decreasing frequency, the thyroid changes associated with hyperthyroidism in cats include multinodular adenomatous hyperplasia (goiter), thyroid adenomas, and atypical thyroid adenoma.

Figure 1. Cat with hyperthyroidism exhibiting weight loss and unkempt hair coat (Courtesy of Noah's Arkive, University of Georgia).

Feline hyperthyroidism was first diagnosed in 1979, when clinical reports of its existence began to emerge. This disease has been diagnosed with increased frequency since that time, and it is now considered the most common endocrine disorder of cats. The increased frequency of diagnosis of feline hyperthyroidism can be attributed to increased clinical awareness of the disease, improved diagnostic testing, an increasing feline population, increased lifespan of pet cats, and the fact that more owners seek veterinary aid for their pets.⁹

Histologic Lesions of the Thyroid Gland

Multinodular adenomatous hyperplasia is observed commonly and consists of small, multifocal nodules spread throughout the thyroid gland. These nodules vary in size and contain irregularly arranged, colloid-filled follicles. Thyroid adenomas usually are large, solitary, nonencapsulated masses. Microscopically, thyroid adenomas consist of irregularly arranged follicles with variable amounts of colloid. Atypical adenomas have a smooth capsular surface and contain larger cells within the neoplasm. Thyroid adenocarcinomas are uncommon malignancies in cats and usually do not cause hyperthyroidism. Thyroid adenocarcinomas metastasize via vascular invasion.¹

Risk Factors for Development of Hyperthyroidism

Proposed risk factors for the development of hyperthyroidism include cats eating canned food or using cat litter, as well as environmental factors such as exposure to other goitrogenic compounds including phthalates. Cats have a relatively slow capacity for glucoronidation, the metabolic pathway responsible for metabolizing many goitrogenic compounds. Autoantibodies have been suggested as a risk factor for the development of hyperthyroidism, but have not been proven to exist in hyperthyroid cats. A genetic basis for hyperthyroidism also has been suggested. Decreased expression of a G-protein in adenomatous thyroid glands of some hyperthyroid cats has been shown to reduce the negative inhibition of the cAMP cascade in thyroid cells. This leads to autonomous growth of the thyroid and the hypersecretion of thyroxine.⁴ The results of one study indicated that overexpression of the c-ras oncogene in hyperthyroid cats was highly associated with areas of nodular follicular hyperplasia and adenomas of the thyroid glands.⁸ Currently, the precise etiology of hyperthyroidism is unclear.

Clinical Signs and Their Proposed Causes

The clinical signs of feline hyperthyroidism are presented in Table 1, along with their frequency of occurrence and probable cause.

Table 1. Frequency and proposed causes of clinical signs in cats with hyperthyroidism.²

Diagnosis

The diagnosis of feline hyperthyroidism by veterinarians usually requires the combination of a detailed medical history, thorough physical examination, and confirmation of disease via laboratory testing. The medical history should note any changes in activity, behavior, or appearance that are suggestive of hyperthyroidism (Table 1).

Thyroid palpation is important in the detection of thyroid gland abnormalities. Palpation is best performed by raising the cat’s chin to a 45º angle and turning the head 45º to the right, placing the left index finger in the groove between the trachea and muscles to the left of the larynx. The index finger should be moved downward to the thoracic inlet. The direction of the head should be reversed and palpation repeated to examine the right cervical area. Palpation can be highly sensitive in detecting hyperthyroid cats, but many euthyroid cats also may possess palpable goiters.¹⁰ However, a large number of elderly, euthyroid cats with palpable goiters ultimately develop hyperthyroidism.¹⁰

Hypertyroid heart disease and cardiac disturbances also are quite common in hyperthyroid cats (Fig. 2). These changes include tachycardia (rapid heart rate), murmurs, premature beats, or gallop rhythms. These findings generally are attributed to the high-output cardiac state caused by the effect of excess thyroid hormone on cardiac muscle as well as its effects on the sympathetic nervous system.²

Figure 2. Lateral and ventrodorsal radiographs of a cat with hyperthyroidism and hyperthyroid heart disease. Notice the enlarged cardiac silhouette (Courtesy of Noah's Arkive, University of Georgia).

CBC and Biochemical Profile

Once hyperthyroidism is suspected, both routine and thyroid-specific laboratory testing are performed to confirm the disease. Complete blood cell counts are usually within the reference interval; however, approximately 50% of hyperthyroid cats have mild erythrocytosis. Erythrocytosis may be a result of thyroid hormone enhanced bone marrow stimulation via beta-adrenergic receptor increase, or stimulation of erythropoietin production. Serum biochemical profiles of hyperthyroid cats have a few characteristic alterations. Increased alanine aminotransferase (ALT) and alkaline phosphatase activities (hepatic enzymes) occur in > 75% of diseased cats, and > 90% exhibit increased activity in one enzyme or the other. Increased hepatic enzyme activity could occur from malnutrition, congestive heart failure, direct hepatotoxic effects of thyroid hormones, or a combination of the three. Hepatic hypoxia is another possible cause of elevated hepatic enzyme activity by increasing oxygen and metabolic demands associated with excessive thyroid hormones in the presence of an unchanged blood flow to the liver.²

T4 and T3 Determinations

The diagnosis of hyperthyroidism usually is confirmed quickly by measurement of serum T4 and T3 concentrations, which are elevated in most cats with the disease. Diagnosis of hyperthyroidism becomes more difficult if the T4 and T3 values are within the reference interval. This occurs in approximately 10% of cats with hyperthyroidism.⁷ This situation can occur if the cat is only mildly hyperthyroid, if nonthyroidal illness is present, or if certain drugs have been administered.

If the clinician still feels that the cat is hyperthyroid with normal T4 and T3 values, a variety of other diagnostic tests remain. The T3 suppression test operates on the principle that administration of exogenous T3 will suppress the release of pituitary TSH in normal cats, resulting in lowered T4 and T3 secretion from the thyroid gland. The T3 suppression test involves measurement of the basal serum T4 and T3 concentrations. Multiple doses of exogenous T3 (liothyronine) are given to the cat at a dose of 25 mg every 8 hours for 2 days. The T4 and T3 concentrations are evaluated 4 hours after the final dose of T3.³ Since thyroid hormone secretion is autonomous in hyperthyroid cats, the T4 concentrations should fail to suppress to the degree of healthy cats or cats with nonthyroidal illness.³ Problems with the T3 suppression test include the length of time required as well as the need for strict owner compliance.

Another method to detect hyperthyroidism is the thyrotropin-releasing hormone (TRH) stimulation test. TRH is the hormone released by the hypothalamus that subsequently stimulates the release of TSH from the pituitary gland. This test requires the determination of baseline T4 concentrations. TRH (0.1 mg/ kg body weight) is administered and the T4 concentration is determined 4 hours later. Since autonomous secretion of T4 and T3 suppresses TSH production and release, most cats with hyperthyroidism do not respond by producing as large an increase in T4 concentration as healthy cats or cats with nonthyroidal disease.¹² Disadvantages of the TRH stimulation test include transient but severe side effects from TRH administration such as salivation, vomiting, tachypnea, and defecation.¹¹

Another test for the confirmation of feline hyperthyroidism is the measurement of free T4 concentration by dialysis. The free T4 concentration is that circulating T4 which is unbound to carrier proteins. Free T4 is metabolically active; its measurement could give a more accurate assessment of thyroid function.⁶ Free T4 is also less likely to be affected by nonthyroidal disease or drug administration than is total T4. The free T4 test is significantly more sensitive in detecting hyperthyroidism in mildly hyperthyroid cats than either total T4 or T3 measurements. However the free T4 test occasionally has a false positive test result, so hyperthyroidism should not be diagnosed solely on the basis of free T4 determination.¹¹ Other clinical signs such as a palpable thyroid nodule, weight loss, etc. (Table 1) also should be present for a definitive diagnosis of hyperthyroidism.

Treatment

The three main methods to treat feline hyperthyroidism include surgical removal of the abnormal thyroid gland tissue, prescription of antithyroid medication, and use of radioactive iodine.² Medical treatment, if used alone, only controls the disease and does not cure it. The two drugs most commonly used are methimazole and carbimazole (not currently available in the US). These drugs are normally given daily as an oral medication. Methimazole inhibits thyroid peroxidase, which is necessary for three of the synthetic steps involved in the formation of thyroid hormones. Methimazole can produce side effects including anorexia, vomiting, lethargy, hematologic problems, hepatopathy, and self-induced facial excoriations. Transdermal treatment is a promising new route of methimazole delivery that appears to avoid many of these side effects.⁵ Treatment of hyperthyroidism also may exacerbate azotemia.¹ Other miscellaneous medical treatments include propylthiouracil and ipodate, which are not nearly as effective as methimazole. Beta-adrenoreceptor blocking agents may be used to control some of the side effects of hyperthyroidism such as hyperexcitability, tachycardia, and tacypnea.²

Curative treatments for feline hyperthyroidism include surgery and radioactive iodine treatment. Both techniques can be quite effective in treating hyperthyroidism. However, post-surgical complications may include hypoparathyroidism, Horner’s syndrome, and laryngeal paralysis. These complications may arise due to the anatomic location of the thyroid gland and its close proximity to structures such as the sympathetic nerve trunk, parathyroid glands, and recurrent laryngeal nerve. Radioactive iodine treatment with iodine-131 is the curative treatment of choice due to its noninvasive nature and extremely high success rate (only about 2 to 4% of cats require a second treatment) (Fig. 3). The main disadvantages of radioactive treatment are the 10-day period of hospitalization required by the average cat and the expense of treatment.²

Figure 3. Localization of iodine-131 in the thyroid glands of a cat with hyperthyroidism (Courtesy of Noah's Arkive, University of Georgia).

References

1. DiBartola SP, Broome MR, Stein BS, et al. (1996) Effect of treatment of hyperthyroidism on renal function in cats. J Am Vet Med Assoc 208:875-878.

2. Feldman EC, Nelson RW. (1996) Feline Hyperthyroidism. In: Canine and Feline Endocrinology and Reproduction, 2nd ed. Philadelphia, Oxford University Press, pp.1447-1479.

3. Graves TK, Peterson ME. (1992) Occult Hyperthyroidism in Cats. In: Current Veterinary Therapy XI. Philadelphia, W.B. Saunders Co., pp.334-336.

4. Hammer KB, Holt DE, Ward CR. (2000) Altered expression of G proteins in thyroid gland adenomas obtained from hyperthyroid cats. Am J Vet Res 61:874-879.

5. Hoffman G, Marks SL, Taboada J, et al. (2003) Transdermal methimazole treatment in cats with hyperthyroidism. J Feline Med Surg 5: 77-82.

6. Kaptein EM. (1993) Clinical application of free thyroxine determinations. Clin Lab Med 13:653-672.

7. McLoughlin MA, DiBartola SP, Birchard SJ, et al. (1993) Influence of systemic nonthyroidal illness on serum concentrations of thyroxine in hyperthyroid cats. J Am Animal Hosp Assoc 29:227-234.

8. Merryman JI, Buckles EL, Bowers G, et al. (1999) Overexpression of c-ras in hyperplasia and adenomas of the feline thyroid gland: An immunohistochemical analysis of 34 cases. Vet Pathol 36, 117-124.

9. Mooney CT. (2002) Pathogenesis of feline hyperthyroidism. J Feline Med Surg 4: 167-169

10. Norsworthy GD, Adams VJ, McElhaney MR, et al. (2002) Relationship between semi-quantitative thyroid palpation and total thyroxine concentrations in cats with and without hyperthyroidism. J Feline Med Surg 4:139-143.

11. Peterson ME, Melian C, Nichols R. (2001) Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. J Am Vet Med Assoc 218:529-536.

12. Peterson ME, Broussard JD, Gamble DA. (1994) Use of the thyrotropin releasing hormone stimulation test to diagnose mild hyperthyroidism in cats. J Vet Intern Med 8:279-286.

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