in Conference Proceedings. New York State Veterinary Conference 2012;2.
Despite more than 30 years of investigation, and strong clinical suspicions of an environmental and/or dietary mechanism, the exact etiology of feline hyperthyroidism remains elusive. The pathophysiologic basis for the disease is comparatively much better defined. The large majority of cats that develop hyperthyroidism have one or more benign thyroid adenomas or adenomatous thyroid hyperplasia. The incidence of thyroid carcinoma causing hyperthyroidism in cats is relatively low, typically being reported as something less than 3 percent. In the normal thyroid cell, binding of TSH to the TSH receptor stimulates growth and differentiation as well as the subsequent secretion of thyroid hormones. This dependence on circulating TSH levels for stimulation of thyroid growth as well as thyroid hormone production renders the thyroid under the control of the hypothalamic-pituitary-thyroid axis. Circulating
thyroid hormones suppress release of TSH from the pituitary by feedback inhibition thus moderating both thyroid growth and ongoing thyroid hormone production. The adenomas responsible for causing feline hyperthyroidism function autonomously, producing thyroid hormone without the need for TSH stimulation. This independence from the hypothalamic-pituitary-thyroid axis is the underlying basis for the thyrotoxicosis that causes the clinical signs observed with this disease.
This lack of dependence on circulating TSH also unleashes these cells from the mechanism normally responsible for regulating thyroid cell growth. As a result the thyroid adenomas in these cats continue to grow despite very low levels of circulating TSH. The most apparent consequence of the progressive growth of the thyroid adenomas responsible for hyperthyroidism is the progressive increase in circulating thyroid hormone levels in these cats. When managing these patients medically, the increase in the number of thyroid cells autonomously producing thyroid hormone is responsible for the need to periodically increase the dose of antithyroid medication required to achieve euthyroidism.
Successful therapy with surgery or radioiodine removes or destroys the adenomatous tissue responsible for the disease. As a result patients managed with these curative modalities do not progress to develop large goiters. Successful medical management however, allows some hyperthyroid cats to live with progressively enlarging thyroid tumors for years and potentially develop very large goiters. Occasionally larger thyroid tumors develop areas of cystic degeneration that can lead to further rapid growth of the mass. And a recent report suggests a relationship between the duration of hyperthyroidism and the incidence of malignant transformation leading to the development of thyroid carcinoma.
Ultimately medical management fails in many of these cats either because the doses of antithyroid drugs needed to control their escalating thyrotoxicosis reach toxic levels or because they develop symptoms (e.g., dysphagia, dyspnea) associated with the large physical size of their goiter. When this happens curative therapies are indicated. When evaluating patients with chronic hyperthyroidism, thyroid scintigraphy plays a critical role in staging the disease. While surgery remains a viable option in many of these cats, the presence of adenomatous thyroid tissue within the thoracic cavity as well as the development of malignant transformation with metastasis often preclude successful surgical intervention. Radioiodine therapy is the only viable therapy in many of these cases.
The standard doses (i.e., 3-6 mCi) of radioiodine used to treat cats with hyperthyroidism typically fail when administered to patients with large goiters. Radioiodine treatment failures in patients with large thyroid masses may be due to the increased number of benign neoplastic cells or a relative radiation resistance of malignant tumors. Typically large, ablative doses of I-131 (i.e., 30 mCi) are needed to resolve these tumors. While the use of these large doses is generally well tolerated, a somewhat higher incidence of regional symptoms including transiently decreased appetite (presumably secondary to esophageal inflammation) and transient cervical edema are noted. The incidence of post radioiodine therapy hypothyroidism is also increased following these large doses, frequently necessitating the use of chronic thyroid hormone supplementation.