Treatment Options and Considerations for Hyperthyroid Cats

The underlying cause of the thyroid tumors (adenomatous hyperpla­sia, adenoma, or carcinoma) associated with feline hyperthyroidism is not known. Because sponta­neous remission of hyperthyroidism in cats does not occur, the aim of treatment is to control the excessive secretion of thyroid hormone from the adenomatous thyroid gland.

The 4 Treatment Options 

In cats, hyper­thyroidism can be treated in four ways — surgical thyroidectomy, radioactive io­dine (131-I), chronic administration of an antithy­roid drug, or lifelong feeding of an ultra-low iodine diet. Each form of treatment has advantages and disadvantages, which must be considered when formulating the best treatment plan for the individual hyperthyroid cat.

Formulating the Best Form of Treatment for Each Cat

The treatment of choice for an individual cat depends on several factors, including the age of the cat, presence of associated cardiovascular dis­eases or other major medical problems (e.g., chronic kidney disease), availability of a skilled surgeon or radioiodine treatment facility, and owner's preference.

The cost of therapy is a major consideration for many cat owners. Medical treatment or use of low-iodine dietary therapy costs far less initially. However, the cost of ongoing monitoring can exceed that of thyroidectomy or radioiodine therapy over a period of many months to years.

Cure versus Control of Hyperthyroidism

Of the four forms of treatment avail­able, it must be emphasized that only surgery and radioactive iodine remove and destroy the thyroid tumors, respectively, and thereby "cure" the hyper­thyroid state.

Use of an antithyroid drug (e.g., methimazole or carbimazole) will block thyroid hormone synthesis. And chronic feeding of an iodine deficient diet will reduce the production of T4 and T3 by the thyroid tumor. However, because antithyroid drugs and low-iodine diets do not de­stroy the hyperthyroid cat’s thyroid tumor(s), hyperthyroidism will recur once antithyroid drugs or dietary therapy is discontinued.

Outline of Treatment

Over the next few weeks, I’ll be discussing each of the four treatment options for hyperthyroidism in some detail. In my next post, however, l will review a frequently neglected but very important part of any of the treatment options — that is, providing the hyperthyroid cat with proper nutrition and adequate amounts of water.

Hyperthyroid cats develop many muscle wasting as well as many metabolic complications because of their disease. Therefore, they have special dietary needs and require a high-quality nutrients in their daily diet including adequate amounts of water, protein, fat, vitamins, and minerals.

References

1. Birchard SJ, Peterson ME, Jacobson A:  Surgical treatment of feline hy­perthyroidism:  Results of 85 cases.  Journal of the American Animal Hospital Association 1984;20:705-709.
2. Peterson ME, Kintzer PP, Hurvitz AI: Methimazole treatment of 262 cats with hyper­thyroidism. Journal of Veterinary Internal Medicine 1988;2:150-157.
3. Welches CD, Scavelli TD, Matthiesen DT, Peterson ME: Occurrence of problems after three techniques of bilateral thyroidectomy in cats. Veterinary Surgery 1989;18:392-396.
4. Peterson ME, Becker DV: Radioiodine treatment of 524 cats with hyperthyroidism. Journal of the American Veterinary Medical Association  1995;207:1422-1428.
5. Peterson ME: Radioiodine treatment for hyperthyroidism. Clinical Techniques in Small Animal Practice 21:34-39, 2006
6. Peterson ME: Hyperthyroidism, In: Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Fifth Edition). Philadelphia, WB Saunders Co. 2000; pp 1400-1419.
7. Peterson ME: Hyperthyroidism in cats. In: Melian C (ed): Manual de Endocrinología en Pequeños Animales (Manual of Small Animal Endocrinology). Multimedica, Barcelona, Spain, 2008, pp 127-168.
8. Peterson ME: Radioiodine for hyperthyroidism. In: Bonagura JD, Twedt DC  (eds): Current Veterinary Therapy XIIII.  Philadelphia, Saunders Elsevier, 2009, pp 180-184.
9. Mooney CT, Peterson ME: Feline hyperthyroidism, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, 2012; in press
10. Baral R, Peterson ME: Thyroid Diseases, In: Little, S. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders, 2012; in press.
11. Peterson ME: Hyperthyroidism in cats, In: Rand, J (ed), Clinical Endocrinology of Companion Animals. New York, Wiley-Blackwell, 2012; in press.

Hyperthyroid in Cats: Table of Contents

As you know if you have been following this blog, I've spent much of the last few months writing about issue of hyperthyroidism, the most common endocrine disorder of the cat.

Before I move on to the topics of treatment of this common feline condition, I thought I'd post links to the topics I've covered thus far:

1. Do All Hyperthyroid Cats Have a Thyroid Tumor? Is It Thyroid Cancer?
2. Why Has Hyperthyroidism in Cats Reached Epidemic Levels?
3. Top 10 Signs of Hyperthyroidism in Cats
4. Top 12 Physical Exam Findings in Cats with Hyperthyroidism
5. Diagnosing Hyperthyroidism in Cats: Routine Testing Procedures
6. Diagnosis of Hyperthyroidism in Cats: Serum T4 Concentrations
7. Diagnosis of Hyperthyroidism in Cats: Serum T3 Concentrations
8. Diagnosis of Hyperthyroidism in Cats: Serum Free T4 Concentrations
9. Diagnosis of Hyperthyroidism in Cats: Serum Free T4 (Part 2)
10. Diagnosis of Hyperthyroidism in Cats: Serum Free T3 Concentrations
11. Diagnosis of Hyperthyroidism in Cats: Serum TSH Concentrations
12. Diagnosis of Hyperthyroidism: T3 Suppression Test
13. Diagnosis of Hyperthyroidism: TRH Stimulation Test
14. Diagnosis of Hyperthyroidism: Thyroid Scintigraphy

I'm halfway through with this "book" on feline hyperthyroidism!

Confirming the Diagnosis of Hyperthyroidism in Cats: Thyroid Scintigraphy

Dr. Mark Peterson performing a thyroid scan on one of his hyperthyroid cat patients

Thyroid scintigraphy (thyroid scanning or thyroid imaging) provides valuable information regarding both thyroid anatomy and physiology and can play an integral role in the diagnosis, staging, and management of thyroid disease in cats with suspected hyperthyroidism.

Thyroid scintigraphy is considered the “gold standard” for diagnosing mild hyperthyroidism in cats (1-3, 6,7). It is considered to be the most sensitive diagnostic test available — yes, even better than determination of serum T4, free T4, or TSH for diagnosis of hyperthyroidism.

 In addition, thyroid scanning is an invaluable tool for evaluating the stage and extent of thyroid tumors (adenomas and carcinomas) in hyperthyroid cats (1,4,5,8).

How Thyroid Scintigraphy Works

To perform thyroid scintigraphy, the specialist injects the cat with a small dose of a radioactive tracer subcutaneously. Over the next hour, the cat’s salivary glands and thyroid glands take up the tracer. The radioactive tracer, now in the salivary and thyroid glands, then emits gamma rays (a high energy electromagnetic wave, a bit stronger than an X-ray), which are detected by a gamma camera to form an image.

To perform thyroid imaging, the cats sits normally on the camera (ventral view) or lies on his or her side (lateral view) while the gamma camera acquires the thyroid image (Figure1, above). The scanning process itself generally takes less than a minute and does not require sedation.

To watch video of Dr. Peterson performing a thyroid scan on a cat with hyperthyroidism, click on this link.

Use of Thyroid Scintigraphy as a Diagnostic Test

In normal cats, the thyroid gland appears on thyroid scans as two well-defined, focal (ovoid) areas of radionuclide accumulation in the cranial to middle cervical region. The two thyroid lobes are symmetrical in size and shape and are located side by side (Figure 2).

Figure 2: Thyroid scan of a normal cat.
Notice  the similar uptake of the radionuclide in the thyroid lobes and the salivary glands.

The normal feline thyroid gland will take up about as much of the tracer as the salivary glands do (see Figure 2). On the scan, we expect the thyroid and salivary glands to be equally bright (a 1:1 brightness ratio).  In addition to visual inspection, we can actually calculate the percent thyroidal uptake of the radioactive tracer as well as the exact the thyroid:salivary ratio. Both of these calculations are strongly correlated with circulating thyroid hormone concentrations and provide a extremely sensitive means of diagnosing hyperthyroidism (6,7).

Figure 3: Thyroid scan of a hyperthyroid cat with a single thyroid adenoma.
Notice  the increased uptake of the radionuclide in the thyroid tumor compared with the salivary glands.

Figure 4: Thyroid scan of a hyperthyroid cat with bilateral thyroid adenomas.
Notice  the increased uptake of the radionuclide in both thyroid tumors compared with the salivary glands.

In hyperthyroid cats, thyroid scintigraphy directly visualizes functional thyroid tissue (Figures 3 and 4). Based up the calculated percent tracer uptake or thyroid:salivary ratio, thyroid imaging can diagnose hyperthyroidism before laboratory tests are consistently abnormal. Thyroid scanning can also prevent misdiagnosis of hyperthyroidism in cats with falsely high serum thyroid hormone values.

More Uses for Thyroid Scintigraphy

Thyroid scintigraphy has four more uses in hyperthyroid cats, other than as a diagnostic test. First, it is an excellent method for evaluating the size of ectopic thyroid tissue, which can be located anywhere from base of the tongue to the heart (Figure 5). Second, it can locate large tumors that gravity has pulled into the thoracic cavity. Finally, thyroid scintigraphy also provides valuable information for diagnosing and evaluating cats with thyroid carcinomas (Figure 6).

Figure 5: Thyroid scan of a hyperthyroid cat with ectopic thyroid adenoma located with the chest cavity. Because of its location, this tumor could not be palpated on physical examination.

Figure 6: Thyroid scan of a hyperthyroid cat with a thyroid carcinoma (cancer). Note the extension of tumor beyond the limits of the normal thyroid capsule. This represents regional metastasis characteristic of carcinoma.

Once we locate a hyperthyroid cat's thyroid tumors on the scan, we can then measure the tumor size and calculate tumor volume (3). This is very helpful in individualizing the cat's dose of radioiodine.

Why Isn't Thyroid Scintigraphy Used More Often?

Apart from expense and the licensing needed to handle and administer radioisotopes, few veterinarians have access to the nuclear medicine equipment needed to obtain thyroid images or perform thyroid uptake determinations. Only a few large referral hospitals in the country offer nuclear scintigraphy to do thyroid scanning.

At the Animal Endocrine Clinic, we routinely perform thyroid scintigraphy on all of our cats in which the diagnosis is not completely clear cut (go to my website for more information).  We believe that thyroid scintigraphy plays an essential role in the diagnosis and management of cats with hyperthyroidism.

References:

1. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clinical Techniques in Small Animal Practice 2006;21:10-16.
2. Daniel GB, Sharp DS, Nieckarz JA, et al. Quantitative thyroid scintigraphy as a predictor of serum thyroxin concentration in normal and hyperthyroid cats. Veterinary Radiology & Ultrasound 2002;43:374-382.
3. Forrest LJ, Baty CJ, Metcalf M.R, et al, Feline hyperthyroidism: Efficacy of treatment using volumetric analysis for radioiodine dose calculation. Veterinary Radiology & Ultrasound, 1996;37:141-145.
4. Harvey AM, Hibbert A, Barrett EL, et al. Scintigraphic findings in 120 hyperthyroid cats. Journal of Feline Medicine and Surgery 2009;11:96-106.
5. Kintzer PP, Peterson ME. Nuclear medicine of the thyroid gland. Scintigraphy and radioiodine therapy. Veterinary Clinics of North America: Small Animal Practice 1994;24:587-605.
6. Mooney CT, Thoday KL, Nicoll JJ, et al. Qualitative and quantitative thyroid imaging in feline hyperthyroidism using technetium-99m as pertechnetate. Veterinary Radiology & Ultrasound 1992;33,313-320.
7. Nap AM, Pollak YW, van den Brom WE, et al. Quantitative aspects of thyroid scintigraphy with pertechnetate (99m TcO4) in cats. Journal of Veterinary Internal Medicine 1994;8:302-303.
8. Peterson ME, Becker DV. Radionuclide thyroid imaging in 135 cats with hyperthyroidism. Veterinary Radiology 1984;25:23-27.

Confirming the Diagnosis of Hyperthyroidism: Thyrotropin-Releasing Hormone (TRH) Stimulation Test

In my last blog post, I discussed use of dynamic test, the T3 suppression test. Suppression testing can be helpful in confirming the diagnosis when we suspect that a cat has mild hyperthyroidism but serum concentrations of total and free T4 are either normal or borderline.

An alternative dynamic test that can be used to help diagnose cats with mild or occult hyperthyroidism is the thyrotropin-releasing hormone (TRH) stimulation test (1-3). Compared with the T3 suppression test, this test takes the opposite approach — now we are stimulating, rather than suppressing, the secretion of TSH from the pituitary, which in turn, would lead to increased T4 secretion.

Thyrotropin-Releasing Hormone (TSH) Stimulation Test

TRH is the hormone released by the hypothalamus that subsequently stimulates the release of thyrotropin (TSH) from the pituitary gland (4). When administered intravenously to normal cats, TRH causes an prompt increase in TSH secretion and serum T4 concentrations (see Figure 1, left panel).

Figure 1: TRH tests in normal cats (left) & cats with hyperthyroidism (right)

In contrast to the situation in normal cats, administration of large doses of TRH to hyperthyroid cats has little or no effect on TSH or T4 secretion. The reason for this that pituitary TSH secretion has already been completely and chronically suppressed by the higher-than-normal thyroid hormone secretion characteristic of hyperthyroidism (see Figure 1 above, right panel).

Administration of only a single dose of TRH is not enough to stimulate chronically suppressed TSH-secreting cells.

Testing Protocol for the TRH Stimulation Test

To perform the TRH stimulation test in cats, the following protocol is recommended:

1. The veterinarian draws a blood sample for determination of baseline serum concentrations of total T4 (and T3).
2. TRH (Protirelin) is administered to the cat at the dosage of 100 μg/kg, IV.
3. Four hours later, the veterinarian again draws a blood sample for serum T4 (and T3) determinations.

One may ask: but what about measuring TSH? Indeed, that would be a more direct measure and would shorten the testing time from 4 hours to less than an hour (4). However, because use of TSH measurements in cats with thyroid disease have only recently been advocated, studies looking the serum TSH response to TRH have yet to be published in cats.

Interpretation of Results of TRH Stimulation Testing

When the TRH stimulation test is performed in normal cats and sick cats without hyperthyroidism (1), there is a consistent rise in serum T4 concentrations (approximately 2-fold rise). In contrast, when the test is performed in cats with hyperthyroidism, even in cats with only slightly high or high-normal resting serum T4 concentrations, there is little, if any, rise in serum T4 values after the administration of TRH (see Figure 2, below).

Figure 2 — Box plots of the serum T4 concentrations before (A) and after (B) TRH stimulation in 31 clinically normal cats, 35 cats with hyperthyroidism, and 15 cats with nonthyroidal disease. The "box" represents the interquartile range from the 25th to 75th percentile (represents the middle one-half of the data). The horizontal bar through the box is the median. The "whiskers" represent the main body of data, which in most cases is equal to the range. Outlying data points are represented by open circles. To convert serum T4 concentrations from nmol/L to µg/dl, divide the given values by 12.87.

Regarding interpretation of the TRH stimulation test results, we found that the relative rise (per cent increase) in serum T4 concentration after administration of TRH was the best (most sensitive) criteria for predicting whether or not cats are hyperthyroid (1). A percent rise in serum T4 of less than 50 per cent is consistent with mild hyperthyroidism, whereas a value of greater than 60 per cent is seen in normal cats; values between 50 and 60 per cent are equivocal or borderline responses.

The serum T3 response to TRH is less helpful in separating normal from hyperthyroid cats, because many normal cats have only a small and inconsistent rise in serum T3 concentrations after TRH administration. Therefore, I do not recommend determining the serum T3 response as part of the TRH stimulation test.

In another study of 36 cats with severe critical illness (5), half of the severely sick cats showed an inadequate T4 response to TRH stimulation test (i.e., a percent rise in serum T4 of less than 50 per cent). Unfortunately, this could create a situation where mild hyperthyroidism is falsely diagnosed in a cat with critical illness.  Although the reason for this is unclear, critical nonthyroidal illness may render pituitary TSH secretion unresponsive to the stimulatory effects of TRH administration.

The bottom line: This test is not meant to differentiate normal and hyperthyroid cats from cats with severe critical illness. I do not recommend doing this test in severely ill cats, inasmuch as the test results may be invalid.

Which is Better: TRH Stimulation Test vs. the T3 Suppression Test?

Advantages of the TRH stimulation test over the T3 suppression test include the shorter time needed to perform the test (4 hours vs. 3 days), and the fact that the TRH stimulation test is not dependent upon the owner's ability to administer oral medication.

The major disadvantage of the TRH stimulation test in cats is that side effects almost invariably occur immediately after administration of the TRH (1, 6-8). These adverse effect include the following:

• Excessive salivation (see Figure 3)
• Vomiting
• Induced defecation
• Rapid breathing (tachypnea); open mouth breathing

Fortunately, all of the adverse side effects are transient and completely resolve by the end of the 4-hour test period. Because of these adverse effects, however, I generally do a T3 suppression test over the TRH stimulation test for dynamic testing of the pituitary-thyroid axis.

Figure 3: Cat showing increased salivation after TRH administration

Our studies show a close relationship between the presence (or absence) of suppressed serum T4 concentrations in response to T3 suppression and stimulated T4 values in response to TRH stimulation. Therefore, although the two tests evaluate the pituitary-thyroid axis in different ways, our findings indicate that the two screening tests provide similar information and can probably be used interchangeably for diagnosing mild hyperthyroidism in cats.

Future Investigations: Serum TSH Response to TRH Stimulation in Cats

In human beings, the TRH stimulation test is generally done by directly evaluating the change in serum TSH concentrations, not indirectly by measuring serum T4  values.  When this is done, the TRH stimulation test is one of the most sensitive tests in detecting early or mild hyperthyroidism in human patients. Again, because TSH production is completely suppressed in hyperthyroid patients, they will not show a rise in serum TSH when TRH is administered, whereas normal individuals will respond with a brisk rise in circulating TSH within 30 minutes of TRH injection. The new, ultra-sensitive human TSH assays have largely eliminated the need for TRH stimulation testing, but it still remains a useful and time-proven test.

Similar serum TSH responses to TRH have been reported in normal dogs — baseline serum TSH concentrations increase 2- to 3-fold when measured 30 minutes after administration of TRH at doses ranging from 1-10 μg/kg. There are two major advantages of evaluating the TSH response rather than the T4 response to TRH:

1. The test period is shorten from 4 hours to only 15-30 minutes.
2. A much lower dose of TRH is needed, greatly reducing or eliminating the adverse signs commonly seen with the higher doses needed to elicit a serum T4 response.

Measuring the serum TSH response to TRH has not been reported in cats with hyperthyroidism. Obviously, this is an area that needs to be investigated, now that we know that the canine TSH assay can be used to measure circulating TSH in cats.

Because the canine TSH assay is not designed to measure low values, basal TSH measurements are not very useful as a diagnostic test in feline hyperthyroidism (see my previous blog on TSH in cats). However, measuring the response to TRH may turn out to be a extremely useful and sensitive test for this disease.

References:

1. Peterson ME, Broussard JD, Gamble DA: Use of the thyrotropin releasing hormone stimulation test to diagnose mild hyperthyroidism in cats. Journal of Veterinary Internal Medicine 1994;8:279-286.
2. Peterson ME. Diagnostic tests for hyperthyroidism in cats. Clinical Techniques in Small Animal Practice 2006;21:2-9.
3. Peterson ME: Diagnostic testing for feline hyper- and hypothyroidism. Proceedings of the 2011 American College of Veterinary Internal Medicine (ACVIM) Forum, pp. 95-97, 2011.
4. Utiger RD: Tests of thyroregulatory mechanisms. In Ingbar SH and Braverman LE (eds): The Thyroid: A Fundamental and Clinical Text, pp 511-523. Philadelphia, JB Lippincott, 1986.
5. Tomsa K, Glaus TM, Kacl GM, et al. Thyrotropin-releasing hormone stimulation test to assess thyroid function in severely sick cats. Journal of Veterinary Internal Medicine 2001;15:89-93.
6. Holtman JR, Buller AL, Hamosh P, et al: Central respiratory stimulation produced by thyrotropin-releasing hormone in the cat. Peptides 1986;7:207-212.
7. Beleslin DB, Jovanovic-Micic D, Tomic-Beleslin N: Nature of salivation produced by thyrotropin-releasing hormone (TRH). Brain Research Bulletin 1987;18:463-465.
8. Beleslin DB, Jovanovic-Micic D, Samardzic R, et al: Studies of thyrotropin-releasing hormone (TRH)-induced defecation in cats. Pharmacology Biochemistry & Behavior 1987;26:639-641.
9. Yagi K, Ohashi E, Tanabe S, Uzuka Y, Sarashina T. Serum thyrotropin response to TRH administration in six healthy beagle dogs. Veterinary Record 2000;146:706-707.