Monday, November 1, 2010

Diagnosis & Treatment of Thyroid Carcinoma in Cats

Hyperthyroidism in cats is most often associated with thyroid adenomatous hyperplasia or adenoma, with carcinomas accounting for only 2% to 3% of cases. While thyroid carcinoma in cats appears to be rare, many cases appear to go undiagnosed, at least in the earlier stages of disease. Diagnosing thyroid carcinoma is very important because standard treatment strategies for hyperthyroidism almost always fail to manage this malignant condition adequately.

Clinical Features of Thyroid Carcinoma in Cats

Most thyroid carcinoma in cats are functional and are associated with typical clinical and biochemical features of hyperthyroidism, such as polyphagia, weight loss, and restlessness. Non-secretory carcinomas also occur in cats and may represent up to a third of cats with thyroid carcinoma; such cats are euthyroid and usually present because of the incidental discovery of a moderate-sized to large cervical mass.

Whether the cat is hyperthyroid or euthyroid cannot, however, determine the carcinoma's capacity to take up and concentrate radionuclide. With thyroid scintigraphy, about half of euthyroid cats with thyroid carcinoma show some degree of radioisotope uptake, indicating that radioiodine may still be a useful treatment in a subset of these cats.

How to Distinguish Thyroid Carcinoma from Adenoma (Adenomatous Hyperplasia)

The clinical features of hyperthyroid cats with thyroid carcinoma are similar those of hyperthyroidism cats with benign adenoma (or adenomatous hyperplasia). Features that should increase one's suspicion for thyroid carcinoma include the following:

  • Larger-than-expected goiter; sometimes multiple, nodular thyroid masses
  • Long history of hyperthyroidism (> 2 years)
  • Extremely high serum T4 concentration (> 5 to 10-times the upper limit of normal)
  • Lack of response to high doses of methimazole or carbimazole (> 15-20 mg/day)
  • Failure or recurrence of hyperthyroidism after thyroidectomy or radioiodine therapy
  • Locally invasive or highly vascular thyroid tumor (usually noted at surgery)
  • Multifocal, irregular, and heterogeneous areas of increased radionuclide uptake with thyroid imaging
  • Signs of distant metastases on radiography or thyroid imaging (usually pulmonary)
In a few cats with thyroid carcinoma, however, very few of the above features will apply. Alternatively, it is possible for a cat with advanced benign disease to show some of the same features (e.g., large goiter, long history of hyperthyroidism, very high serum T4 value).

Thyroid carcinoma can be extremely variable on palpation (if in the cervical region), ranging from discrete solitary mobile nodules, to chains of tissue extending along the neck or fixed firm masses. Both benign and malignant thyroid tumors may become extremely large if cystic changes develop. Gross appearance at surgery, however, may be more informative since thyroid carcinomas frequently infiltrate local tissues and are highly vascular.

An inadequate response to conventional treatment in any hyperthyroid cat should raise the question of a possible thyroid carcinoma. For example, if hyperthyroidism is not controlled or quickly recurs after bilateral thyroidectomy or standard doses of radioiodine fail to cure the cat's hyperthyroidism, thyroid carcinoma must be considered.

Many cats eventually diagnosed with thyroid carcinoma had initially been controlled fairly well with antithyroid drugs. Although these drugs are typically effective in suppressing serum T4 concentration for variable periods, the daily dose requirement needed to control the hyperthyroid state gradually and progressively increases in these cats. Eventually, the thyroid tumor will grow to such a size that antithyroid drug therapy, no matter what the dose, no longer blocks T4 secretion from the large volume of carcinomatous tissue.

Scintigraphic features that can help distinguish malignant from benign thyroid disease include multiple and extensive areas of hyperfunctional thyroid tissue, a heterogeneous pattern of radioisotope uptake with irregular margins, linear multifocal patterns (suggestive of tumor extension along fascial planes), and uptake of masses within the cranial mediastinum. A recent review of scintigraphic findings in hyperthyroid cats, however, found that similar imaging changes are occasionally observed in cats with benign disease (Harvey et al. 2009). The identification of metastatic disease in thyroid carcinoma is complicated by the existence of ectopic thyroid tissue in up to 25% of cats. Hence, multiple areas of radioisotope uptake in the cervical or intra-thoracic locations (or both) could potentially reflect metastases or multiple primary tumors in ectopic sites.

Despite its limitations, thyroid scintigraphy remains a valuable and essential tool in evaluating a cat with suspected thyroid carcinoma. Thyroid imaging is the best means we have to assess tumor functionality and determine thyroid volume to assist in treatment planning with surgery or high-dose radioiodine.

Thyroid image performed in a 12-year-old cat with a 3-year history of hyperthyroidism.
This cat was no longer responsive to methimazole therapy. Notice the large multiple thyroid masses. Most of this cat's thyroid tumor was located within the thoracic cavity (the yellow horizontal line indicates the region of the thoracic inlet). For comparison, a thyroid scan from a normal cat is shown on the right.
Definitive Diagnosis of Thyroid Carcinoma
The only definitive way to confirm a diagnosis of thyroid carcinoma is by histopathologic examination. Pathological criteria for malignancy include extracapsular invasion, vascular invasion, cellular pleomorphism, and increased mitotic activity.

Definitive identification of thyroid carcinoma on histopathology generally necessitates excisional biopsy. Routine histopathology of the thyroid tumor should always be done after any thyroid surgery. Because many thyroid carcinomas are highly vascular, excision may be difficult and hemorrhage may occur; in these cats, it may not be possible to do a thyroidectomy, but one should at least attempt to obtain a biopsy for diagnosis.

Scintigraphy can be used adjunctively, especially in recognizing regional and distance metastasis. But again, scintigraphy alone cannot reliably distinguish whether the thyroid tissue is malignant since ectopic thyroid tissue commonly is found in cats with benign thyroid disease.
Interestingly, mixed adenoma and carcinoma tissue has been documented in some cats with thyroid carcinoma. This strongly suggests that, at least in some cats, thyroid carcinoma appear to arise from transformation of benign into malignant neoplasia.

Treatment of Cats with Thyroid Carcinoma

Radioiodine is considered the gold standard treatment for hyperthyroidism. It has the advantages of treating all hyperfunctional tissue, regardless of site (including ectopic thyroid tissue). In addition, there is no need for general anesthesia and treatment complications are minimal with radioiodine therapy. The efficacy of radioiodine is well established in cats with benign disease, with success rates of up to 94% reported (Peterson & Becker, 1994).

The use of radioiodine for treatment has also been reported in a limited number of cats with thyroid carcinoma. Higher 131I doses are required for cats with thyroid carcinoma (3-10 x higher than for benign disease), primarily because of the much larger tumor volume associated with carcinoma. In addition, at least in euthyroid cats with thyroid carcinoma, the malignant tissue appears less efficient at taking up and concentrating radioiodine. Therefore, higher administered 131I doses are needed in order to have enough 131I taken up by the tumor to destroy the carcinomatous tissue.

Most studies of cats with thyroid carcinoma have used an empirical high 131I dose of 30 mCi (1110 MBq). With this protocol, long-term prognosis is good with extended survival commonly achieved (Guptill et al. 1995; Hibbert et al. 2009).

In one recent study, 12 hyperthyroid cats with hypersecretory thyroid carcinomas were treated with high-dose radioiodine. Of these, treatment was successful in 11 cats, with complete resolution of hyperthyroidism and extended survival times (median 1,065 days). The remaining cat had a partial response.

Thyroid images of a cat with thyroid carcinoma before (left) and after (right) treatment
with high-dose radioiodine therapy. Notice that the thryoid carcinoma in this cat
has been completely destroyed.

The combination of surgical debulking followed by administration of high-dose radioactive iodine also has been reported to be successful in cats with thyroid carcinoma. This allows one to obtain thyroid tissue for histopathologic examination in order to confirm thyroid carcinoma. Because the total tumor volume is lessened by the debulking procedure, a lower 131I dose is generally needed to destroy the remaining tumor tissue. However, if excision biopsy is not possible, higher doses of 131I will be needed, necessitating a longer hospital stay. Unfortunately, many of these cats are not surgical or anesthetic candidates because of their severe, advanced, and uncontrolled hyperthyroidism.

Optimal treatment of non-secretory thyroid carcinoma remains unclear. Although some euthyroid cats treated with 131I have had least temporary remission of thyroid carcinoma, it is likely that these cats would respond better to a combination of surgery and external beam radiotherapy, similar to the management of canine thyroid carcinomas.

In conclusion, thyroid carcinoma is a relatively rare (but increasing common) cause of feline hyperthyroidism. Although there are many clinical and imaging features that suggest thyroid carcinoma, diagnosis can only be made by histopathologic examination of tissue. Treatment with high-dose radioiodine is clearly the best therapeutic option. Successful response to radioiodine is associated with prolonged survival times, comparable to those achieved in hyperthyroid cats with benign disease.


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