Diagnosing Hypothyroidism in Dogs

I have a 7-year old spayed Golden Retriever who weighs about 110 lbs. No signs of hypothyroidism except for being overweight with a borderline high serum cholesterol concentrations (256 mg/dl). The serum T4 value was slightly low at 0.9 µg/dl (reference interval, 1.0-4.0 µg/dl).

Is this slightly low serum T4 concentration diagnostic for hypothyroidism? Would you start her on levothyroxine (L-T4) and retest T4 levels in a month?

I'd appreciate your thoughts and recommendations.

My Response: 

I would never base the diagnosis on only a resting serum T4 value alone. We commonly find low values that fluctuate in and out of the reference range in dogs that are clinically normal and never develop hypothyroidism. In addition, most non-thyroidal illness will lower the total T4 values in dogs, and these dogs would not benefit from thyroid hormone supplementation (1). It certainly doesn't sound like your dog is sick or acting ill in any way, so this latter explanation probably doesn't apply here.

For your dog, I'd recommend that your veterinarian collect more sera to do a complete thyroid panel, which should include the following tests (2-4):

• Serum T4 concentration
• Serum T3 concentration
• Serum free T4 by dialysis
• Serum TSH concentration
• Serum levels of thyroglobulin autoantibodies

If you have it available in your area, thyroid scintigraphy (nuclear medicine scan) is actually the best and most accurate way to diagnose hypothyroidism in dogs (4.5).

 References: 

1. Kantrowitz LB, Peterson ME, Melian C, et al. Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease. J Am Vet Med Assoc 2001;219:765-769. 
2. Peterson ME, Melian C, Nichols R. Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of hypothyroidism in dogs. J Am Vet Med Assoc 1997;211:1396-1402.  
3. Nachreiner RF, Refsal KR, Graham PA, et al. Prevalence of serum thyroid hormone autoantibodies in dogs with clinical signs of hypothyroidism. J Am Vet Med Assoc 2002;220:466-471. 
4. Diaz Espineira MM, Mol JA, Peeters ME, et al. Assessment of thyroid function in dogs with low plasma thyroxine concentration. J Vet Intern Med 2007;21:25-32.  
5. Shiel RE, Pinilla M, McAllister H, et al. Assessment of the value of quantitative thyroid scintigraphy for determination of thyroid function in dogs. J Small Anim Pract 2012;53:278-285. 

Thyroid Scintigraphy for Diagnosis and Staging of Cats to be Treated with Radioiodine

Thyroid scintigraphy 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 (1-5). The procedure is extremely safe, does not require the use of anesthesia, and is cost-effective, especially when considering the costs of an incorrect diagnosis or inappropriate treatment.

What radiosotopes are used for thyroid imaging?
The basis for this procedure is the unique physiology of the thyroid gland that results in the selective uptake of iodide by thyroid tissue (4-7). Although various isotopes of iodine are available for use in thyroid scintigraphy, their concurrent beta emission and associated local tissue damage (e.g., 131-I) or greater expense (e.g., 123-I), have limited their use in veterinary medicine.

The pertechnetate ion has a similar size, molecular shape, and charge compared to iodide, which results in its uptake by thyroid tissue. The radionuclide technetium-99m pertechnetate (99m-TcO4) is a pure gamma emitter with a low photon energy (140 KeV) that makes it ideal for diagnostic imaging (4-7). Because of these properties, as well as the fact that technetium is relatively inexpensive, it has become the radionuclide of choice for routine thyroid imaging in veterinary medicine.

How a thyroid scan is performed in cats
To perform thyroid imaging in cats, a small dose (3-4 millicuries of  technetium is administered subcutaneously. Between 20 to 60 minutes later, the cats are laid on their abdomen (ventral view) or side (lateral view) while the gamma camera acquires the thyroid image. The scanning process itself usually takes less than a minute and generally does not require sedation (4-6).

Fig 1: Thyroid scintigraphy
in a normal cat

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 symmetric in size and shape and are located side by side (Figure 1). 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 calculate the percent thyroidal uptake of the radioactive tracer or the thyroid:salivary ratio. Both of these calculations are strongly correlated with circulating thyroid hormone concentrations and provide an extremely sensitive means of diagnosing hyperthyroidism (4-9).

5 reasons why a thyroid scan is performed
There are five reasons why thyroid scintigraphy should be considered in any cat with suspected hyperthyroidism, especially before radioiodine treatment.

Reason 1— First, thyroid scintigraphy helps confirm the diagnosis of hyperthyroidism, which is very useful in cats in which a thyroid nodule cannot be palpated (4-9). Because thyroid scintigraphy directly visualizes functional thyroid tissue and the “uptake” of the radioisotope can be estimated by determining the thyroid:salivary ratio, thyroid imaging can diagnose hyperthyroidism before laboratory tests are consistently abnormal (Figure 2). Thyroid scintigraphy is considered the gold standard for diagnosing mild hyperthyroidism in cats.

Fig 2: Thyroid imaging in 2 cats with mild hyperthyroidism. The cat on the left has a unilateral thyroid adenoma, whereas the cat on the right has bilateral adenomas. In both cats, notice that the uptake of the radionuclide by the thyroid adenoma(s) is higher than the uptake by the cats' salivary tissue.

Reason 2—Thyroid scintigraphy can also exclude the diagnosis of hyperthyroidism in euthyroid cats that have false-positive elevations in their serum T4 or free T4 values. Studies of cats with nonthyroidal illness (e.g., diabetes, renal, gastrointestinal, or liver disease) have shown that between 6% and 12% of these cats have falsely high serum free T4 values, despite the fact that they are not hyperthyroid (10,11).

In addition, routine screening of an apparently healthy senior cat occasionally reveals laboratory abnormalities that include slightly high total or free T4 concentrations, consistent with mild hyperthyroidism (12). As with sick cats with falsely high free T4 values, however, no thyroid nodule can be palpated in many of these cats and thyroid imaging may fail to confirm hyperthyroidism. Therefore, not every cat with a high total T4 or free T4 value is truly hyperthyroid, and treatment for hyperthyroidism would be contraindicated.

Fig 3: Ectopic thyroid adenoma
in the chest cavity of a hyperthyroid cat

Reason 3—In addition to visualization of functional cervical thyroid nodules, thyroid scintigraphy is an excellent method for evaluating the size of ectopic thyroid tissue, which can be located anywhere from the base of the tongue to the heart (Figure 3).

In addition, thyroid images can locate large tumors that gravity has pulled into the thoracic cavity, which cannot be palpated on physical examination (4-9).

Reason 4— By providing a visual image of hyperfunctional thyroid tissue, thyroid scintigraphy allows for the determination of thyroid tumor mass or volume, which is useful in calculating each cat’s radioiodine dose (6,12,13). The goal of 131-I therapy is to restore euthyroidism with a single dose of radiation without producing hypothyroidism.

Recent research confirms that iatrogenic hypothyroidism contributes to the development of azotemia and shortened survival times in cats overtreated with radioiodine (14). To minimize the incidence of iatrogenic hypothyroidism, it is important to administer the lowest effective dose to each individual cat, rather than giving a fixed dose of radioiodine to all cats (12). Again, thyroid scintigraphy provides an excellent method for evaluating the size of the hyperfunctional thyroid tissue, which aids in determining the proper dose to treat the individual hyperthyroid cat.

Reason 5—Thyroid scintigraphy also provides valuable information in the diagnosis and evaluation of hyperthyroid cats with thyroid carcinoma (Figure 4). Our recent studies suggest that, although thyroid carcinoma is rare in cats with recently diagnosed hyperthyroidism, the prevalence of carcinoma progressively increases in cats treated long term with antithyroid medications. Of cats treated for longer than 4 years with medical treatment, over 20% had scintigraphic evidence of thyroid carcinoma (15).

Fig 4: Thyroid images of 6 hyperthyroid cats with thyroid carcinoma. Notice the large tumor volumes, with extension of disease beyond the limits of the thyroid capsule into the chest cavity in all cases.

The diagnosis of thyroid carcinoma can be challenging (even with histopathology) but without pre-treatment scanning these cases would go undetected. Because of the large tumor volume associated with thyroid carcinoma, as well as the potential for local invasion and metastasis, most of these cats are treated with high doses of radioiodine (e.g., 30 mCi) in order to completely ablate all thyroid tissue (12), thereby curing the cat’s thyroid cancer (Figure 5).

Fig 5: Thyroid images of a hyperthyroid cat with thyroid carcinoma before and after high-dose radioiodine treatment.
Notice the complete ablation of all thyroid cancer tissue 2 months after treatment (right).

Is a thyroid scan mandatory in all cats treated with radioiodine?
No, a thyroid scan is not absolutely mandatory — most treatment facilities in the USA do not do thyroid imaging prior to treatment.

Despite the valuable information obtained by performing thyroid scintigraphy, it is not required prior to radioiodine therapy, just as thoracic radiographs are not required prior to amputating a limb in a patient with a primary bone tumor or a preanesthetic laboratory screening is not required prior to dental prophylaxis or other elective procedures requiring anesthesia. Nevertheless, use of thyroid scintigraphy is considered good medicine because the findings can and do result in modification of the therapeutic dose, aid in the diagnosis of hyperthyroidism, and provide prognostic information.

References:

1. 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; 199-203.
2. Baral R, Peterson ME: Thyroid gland disorders, In: Little, S. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders, 2012;571-592.
3. Peterson ME: Hyperthyroidism in cats In: Rand JS, Behrend E, Gunn-Moore D, et al., eds. Clinical Endocrinology of Companion Animals. Ames, Iowa Wiley-Blackwell, 2013;295-310.
4. Peterson ME, Becker DV. Radionuclide thyroid imaging in 135 cats with hyperthyroidism. Veterinary Radiology 1984;25:23-27. 
5. Daniel GB, Brawnier WR. Thyroid scintigraphy In: Daniel GB,Berry CR, eds. Textbook of Veterinary Nuclear Medicine. 2nd ed. Harrisburg, PA: American College of Veterinary Radiology, 2006;181-199.
6. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clinical Techniques in Small Animal Practice 2006;21,10-16. 
7. Feeney DA, Anderson KL. Nuclear imaging and radiation therapy in canine and feline thyroid disease. Vet Clin North Am Small Anim Pract 2007;37:799-821, viii. 
8. Harvey AM, Hibbert A, Barrett EL, et al. Scintigraphic findings in 120 hyperthyroid cats. J Feline Med Surg 2009;11:96-106. 
9. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2012;26:754.
10. Mooney CT, Little CJ, Macrae AW. Effect of illness not associated with the thyroid gland on serum total and free thyroxine concentrations in cats. J Am Vet Med Assoc 1996;208:2004-2008. 
11. Peterson ME, Melian C, Nichols R. 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 2001;218:529-536
12. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD,Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013;in press.
13. Volckaert V, Vandermeulen E, Saunders JH, et al. Scintigraphic thyroid volume calculation in hyperthyroid cats. J Feline Med Surg 2012;14:889-894. 
14. Williams TL, Elliott J, Syme HM. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. J Vet Intern Med 2010;24:1086-1092. 
15. Peterson ME, Broome MR:  Hyperthyroid cats on long-term medical treatment show a progressive increase in the prevalence of large thyroid tumors, intrathoracic thyroid masses, and suspected thyroid carcinoma. J Vet Intern Med 26:1523,2012.

Thyroid Imaging for Preoperative Staging of Hyperthyroid Cats

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

Ideally, thyroid scintigraphy would be performed in all hyperthyroid cats prior to surgical thyroidectomy to identify the extent and location of the cat's hyperfunctioning thyroid tumor tissue (1-7).  In hyperthyroid cats, thyroid scintigraphy directly visualizes all functional thyroid tissue and will easily reveal whether the hyperthyroid cat has a thyroid tumor affecting only one lobe (unilateral disease) or both lobes (bilateral disease). See the scans in Figure 1 below.

Fig. 1: Thyroid scintigraphy in 3 hyperthyroid cats.
The cat on the left has a single thyroid tumor (Unilateral), whereas the cat on the right has 2 thyroid tumors that involve both thyroid lobes equally (Bilateral symmetric). The cat in the middle panel also has bilateral thyroid disease, but it is possible that the surgeon could mistake the smaller thyroid lobe as normal since the thyroid tumor enlargement is so asymmetric.

Some hyperthyroid cats develop very large thyroid tumors that descend into the chest cavity. making them difficult to palpate or identify at surgery. We often see these tumors in cats that have been hyperthyroid for many months to years (8,9). As the tumor grows progressively larger, gravity pulls progressively harder. This causes the tumor to descend into the chest cavity. Again, thyroid scintigraphy will detect these intrathoracic thyroid tumors that could easily be missed at surgery (Figure 2).

Fig. 2: Thyroid scintigraphy in a hyperthyroid cat with bilateral thyroid tumors.
In this cat, the larger thyroid tumor has descended into the chest cavity because of the effects of gravity. Without thyroid scintigraphy, this tumor could easily be missed at surgery, resulting in persistent hyperthyroidism.

Ectopic thyroid tissue is an embryological phenomenon that we see in about 3-5% of all hyperthyroid cats (8,9).  As the cells that develop into the thyroid gland traverse the embryo, they can leave traces of tissue anywhere from the base of the tongue to the base of the heart. These thyroid remnants can develop into functional thyroid tissue.  If such ectopic thyroid tissue develops a tumor, it will not be palpable or easily found at surgery, especially if the ectopic tumor is located on the tongue or in the chest cavity.  Thyroid scintigraphy can quickly and easily locate these tumors (see Figure 3).

Fig. 3: Thyroid scintigraphy in a hyperthyroid cat with a single ectopic thyroid nodule.
In this cat, no thyroid tumors could be palpated in the neck area where the thyroid gland is normally located. The large thyroid tumor has arisen from ectopic thyroid tissue that is located within the chest cavity. Without thyroid scintigraphy, this tumor could easily be missed at surgery, resulting in persistent hyperthyroidism.

Finally, thyroid scintigraphy also provides valuable information for diagnosing and evaluating cats with thyroid cancer (carcinomas) and metastasis.  With scintigraphy, a carcinoma will appear as a large, irregularly shaped tumor extending beyond the limits of the normal thyroid region (see Figure 4).  We can also see whether the tumor has metastasized or shows local invasion of the surrounding tissues. Thyroid carcinomas account for 2-3% of all thyroid tumors in cats (8,9).

Fig. 4: Thyroid scintigraphy in 6 hyperthyroid cats with a thyroid carcinoma (thyroid cancer).
In these cats with thyroid carcinoma, notice that the thyroid tumors are very large, multinodular, with extension and metastasis into the chest cavity. Surgery is unlikely to be successful in any of these cats, since these cancers are highly vascular and invasive, and it would be difficult to find all malignant thyroid tissue at surgery.

If thyroid scintigraphy is not available, the surgeon will have to make a decision upon what thyroid tissue to remove based on the visual appearance of the glands during surgery. In some cases, the surgeon may be fooled into leaving abnormal functioning thyroid tissue behind, especially if located in the chest cavity. Failure to identify and remove all hyperfunctional tissue will result in failure to cure the cat's hyperthyroidism.

Why Isn't Thyroid Scintigraphy Always Done Prior to Thyroidectomy?

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. However, if available, I believe that thyroid scintigraphy can play an essential role in the preoperative staging and surgical management of cats with hyperthyroidism.

References:

1. 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; 199-203.
2. Baral R, Peterson ME: Thyroid gland disorders, In: Little, S. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders, 2012;571-592.
3. Peterson ME: Hyperthyroidism in cats, In: Rand, J (ed), Clinical Endocrinology of Companion Animals. New York, Wiley-Blackwell, 2012; in press.
4. Panciera DL, Peterson ME, Birchard, SJ: Diseases of the thyroid gland. In: Birchard SJ, Sherding RG (eds): Manual of Small Animal Practice (Third Edition), Philadelphia, Saunders Elsevier, pp 327-342, 2006.
5. Birchard, SJ. Thyroidectomy in the cat. Clinical Techniques in Small Animal Practice 2006;21, 29-33. 
6. Flanders JA. Surgical therapy of the thyroid. Veterinary Clinics of North America. Small Animal Practice 1994;24:607–621. 
7. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clinical Techniques in Small Animal Practice 2006;21,10-16. 
8. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2012;26:754.
9. Peterson ME, Broome MR. Hyperthyroid cats on long-term medical treatment show a progressive increase in the prevalence of large thyroid tumors, intrathoracic thyroid masses, and suspected thyroid carcinoma. Congress Proceedings, 22^nd ECVIM-CA Congress (The European College of Veterinary Internal Medicine – Companion Animals) 2012; 224

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.

Do All Hyperthyroid Cats Have a Thyroid Tumor? Is It Thyroid Cancer?

Yes, all hyperthyroid cats have thyroid tumors – every last one.  However, if your cat is hyperthyroid, there is no need to panic!  Most of the thyroid tumors that cause hyperthyroidism in cats are benign (non-cancerous), so it is very unlikely that your cat has cancer, especially if the hyperthyroid condition was only recently diagnosed.

All thyroid tumors in hyperthyroid cats are made up of thyroid cells that grow and function at an uncontrolled rate. This makes your cat’s thyroid gland grow larger and larger with time.  In almost all hyperthyroid cats, the veterinarian can palpate the thyroid tumor (Figure 1).  In contrast, the veterinarian should not be able to feel a normal cat’s thyroid gland, much less see it! 

Figure 1: A hyperthyroid cat with an extremely large thyroid tumor.

In addition to making the thyroid larger, the tumor cells function at an increased rate and produce too much of the thyroid hormone thyroxine (T4).  This excess thyroid hormone in your cat's circulation is what causes the signs of hyperthyroidism, such as increased appetite, hyperactivity, and weight loss.

Thyroid tumors come in two varieties, adenoma and carcinoma.   Adenomas are by far the majority (97-98%) of tumors that cause hyperthyroidism in cats.  Adenomas are benign tumors; they do not spread (metastasize) to other parts of the body.  The normal feline thyroid gland is made up of 2 small, separate thyroid lobes, both lying adjacent to the trachea (windpipe).  In 70% of hyperthyroid cats, adenoma infiltrates both thyroid lobes (Figure 2), whereas 30% of cats have only one thyroid lobe affected.

Figure 2: Hyperthyroid cat with two thyroid adenomas at time of surgery. In this cat, the left thyroid lobe (top of image) is twice normal size, whereas the right lobe (bottom of image) is 4-6 times normal size. Both thyroid lobes were palpable on physical examination.

In 2-3% of cats, the hyperthyroid condition is caused by thyroid carcinoma, rather than thyroid adenoma.  Unlike adenomas, thyroid carcinomas are cancerous and generally grow to a massive size (Figure 3).  They are malignant tumors – carcinomas invade and metastasize to surrounding tissues, such as the chest cavity, and endanger the cat’s life.

Figure 3: Hyperthyroid cat a large thyroid carcinoma at time of surgery. In this cat, the left thyroid lobe is approximately 50 times normal size. These tumors are invasive and generally inoperable.

Although cats with thyroid carcinomas are harder to treat, radioiodine therapy is the best option.  By administering an ultra-high dose of radioiodine (e.g. up to 10 times the I-131 dose appropriate for an adenoma), it is easily possible to destroy all of the cat’s malignant thyroid tissue.  With this treatment, we can cure the cat of both their cancer and hyperthyroidism!

One question remains: what causes the 2 to 3% of hyperthyroid cats to develop carcinomas?  Again, most cats that have carcinomas have been hyperthyroid for a long time (on the scale of many months to years).  Recent evidence indicates that the tumors change over time in these cats, transitioning from normal tissue to fast growing tissue, soon turning into an adenoma.  When left untreated, or treated only with an anti-thyroid drug (see next week’s article), tumor growth continues and eventually the adenoma tissue transforms into a malignant carcinoma.

How Do We Confirm a Diagnosis of Hypothyroidism in Dogs?

Because of the vague clinical signs and the absence of specific abnormalities on a routine blood test, the diagnosis should be confirmed through a specific evaluation of the thyroid gland. As always, laboratory results should be interpreted in the light of history and physical examination findings. A thorough clinical examination of the patient, knowledge of the advantages and disadvantages of all available tests and knowledge of the factors that can influence the results, will allow the veterinarian to correctly diagnose the disease.

In dogs with suspected hypothyroidism, the clinical suspicion of the disease is obtained by reviewing the dog’s signalment, history, and clinical features. A general blood screening examination, including a CBC, comprehensive chemical panel, and complete urinalysis are next done to look for changes consistent with hypothyroidism and exclude other problems that mimic hypothyroidism.

If hypothyroidism is still suspected, the diagnosis should be confirmed through a specific evaluation of the thyroid gland function. These tests include measurement of serum concentrations of total and free T4, T3, and TSH. The choice of diagnostic test(s) performed are based heavily on the index of suspicion for hypothyroidism.

In some dogs, it may also be necessary to use thyroid scintigraphy to definitely confirm the condition. However, most veterinary offices do not have the equipment needed to do this thyroid scanning procedure.

Thyroid specific evaluation

Total thyroxine (T4)
This test usually used as the initial thyroid specific screening test. If the results of this test are within normal limits, your veterinarian will usually look for other causes of your dog’s clinical signs. Most dogs with hypothyroidism will have low values for T4 compared with healthy dogs. However, dogs that have other diseases can also have low T4, so false-positive T4 results are commonly observed. Again, that is why general laboratory testing must be done in all dogs with suspected hypothyroidism.

This test measures the total amount of thyroxine (abbreviated T4, because it contains 4 iodine molecules) which is the main hormone produced by the thyroid gland. hormone circulating in the blood, which includes both bound and unbound T4 molecules. More than 99% of T4 hormone is “bound,” meaning that it is attached to proteins in the blood, making the bound T4 too big to pass from the circulation into the tissues. A T4 result by itself is can be misleading, inasmuch as it is affected by anything that changes the amount of binding proteins circulating in the blood, such as occurs with drugs and nonthyroidal illness.

Certain kinds of drugs (e.g. sulfa antibiotics, anti-inflammatory, anti-depressant and anti-seizure medication) can cause artificially lowered thyroid levels so it is important to make sure we account for these before making a diagnosis.

In addition, although normal T4 reference levels of healthy adult dogs tend to be similar for most breeds, they do vary depending on age and breed. Puppies, for example, display higher T4 levels than adult dogs, because their bodies need extra hormones as they undergo the maturation process. Compared to the adult dog “normal range,” the optimal thyroid levels for puppies are normally in the high-normal to slightly high range. Conversely, the basal metabolism of geriatric dogs is usually slowing, so optimal T4 levels are likely to be closer to midrange or even slightly lower. Similarly, giant breed dogs have lower basal T4 levels, and Sight hounds as a group have the lowest T4 levels of all the breed categories.

Free T4
Serum free T4 represents the tiny fraction (< 0.1%) of total T4 that is unbound and therefore is biologically active and able to enter the tissues. Since protein levels in the blood do not (or only minimally) affect free T4, it is considered a more accurate test of true thyroid activity than the total T4. Free T4 is much less likely to be influenced by nonthyroidal illness or drugs.

Both total T4 and free T4 are lowered in almost all dogs of hypothyroidism. While most endocrinologists favor the equilibrium dialysis method for measuring free T4, newer technologies offer alternative and accurate assays that are faster and less costly.

Overall, this is a more sensitive indicator of hypothyroidism. Some dogs that are not truly hypothyroid may have a low total T4 but a normal free T4.

Total T3
Measuring serum T3 alone is not considered an accurate method of diagnosing hypothyroidism, as this hormone reflects tissue thyroid activity and is often influenced by concurrent nonthyroidal illness. It is, however, useful as part of a thyroid profile or health screening panel.

Thyroid stimulating hormone (TSH)
Production of thyroid hormones is regulated by the pituitary gland, through a hormone called thyroid-stimulating hormone (TSH). A feedback loop exists between the body and the pituitary gland, with TSH production by the pituitary going up when the body needs thyroid hormone and turning off when thyroid hormone levels are high.

Therefore, dogs with primary hypothyroidism are expected to have high serum TSH concentrations. Unfortunately, the current TSH test used in dogs is associated with a high incidence of false-negative or false-positive results.

Result for serum TSH must be evaluated together with serum T4 (and free T4) concentrations. Finding a low T4, low free T4, and a high TSH concentration is diagnostic for canine hypothyroidism. On the other hand, finding a high TSH level together with normal values for T4 or free T4 does not confirm hypothyroidism and is best ignored (at least for the time being).

Thyroglobulin autoantibody levels
High titers of thyroglobulin autoantibodies are present in the serum of dogs with autoimmune thyroiditis, which is the heritable form of hypothyroidism. Performing this test is especially important in screening breeding stock for autoimmune thyroiditis, as dogs testing positive for thyroglobulin autoantibodies should not be bred.

This is not in any way a stand-alone test for hypothyroidism and evaluation of additional tests is necessary to determine whether a dog is hypothyroid.

Thyroid Scintigraphy (Scanning)
Thyroid scintigraphy provides valuable information regarding both thyroid anatomy and physiology and can play an integral role in the diagnosis of thyroid disease in dogs or cats. Although rarely used to diagnose hypothyroidism, is now clear that thyroid imaging is also the best way to confirm the diagnosis of that common disorder. At the Animal Endocrine Clinic, we have the equipment needed to perform thyroid scintigraphy and we readily use this in the diagnosis of dogs and cats with thyroid disease. For more information about thyroid scans, please visit our Nuclear Imaging Facebook page.

In normal dogs, the thyroid gland appears on thyroid scans as two well-defined, focal (ovoid) areas of uptake in the cranial to middle cervical region. The two thyroid lobes are symmetrical in size and shape and are located side by side. Activity in the normal thyroid closely approximates activity in the salivary glands, with an expected “brightness” ratio of 1:1.

In dogs with hypothyroidism, thyroid scanning typically reveals decreased or even absent thyroid uptake (thyroid gland is not at all visible on the scan). In contrast, dogs that have falsely low serum thyroid hormone concentrations secondary to illness or drug therapy have a normal thyroid image.

Is Thyroid Scanning Useful in Cats with Hyperthyroidism?

Thyroid scintigraphy (thyroid scanning by nuclear imaging) is a powerful imaging technique for visualizing thyroid tumors.  Only a few specialized facilities (such as the Animal Endocrine Clinic) have the equipment and special licensing required to perform scintigraphy.  In this week’s blog, I will be discussing how thyroid scintigraphy works, and its four main uses: diagnosing hyperthyroidism, locating impalpable tumors (tumors that cannot be felt on exam), diagnosing thyroid carcinomas, and calculating a radioiodine dose.

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.

Thyroid scintigraphy for diagnosing hyperthyroidism
Sometimes, even an endocrinologist will have trouble telling whether a cat is hyperthyroid.  Its T4 values may be on the borderline of abnormal, and the tumor may be difficult to palpate.  Thyroid scintigraphy is the “gold standard” for determining whether the cat is hyperthyroid.

In a normal cat, the thyroid gland will take up about as much of the tracer as the salivary glands do (see Figure 1).  On the scan, we expect the thyroid and salivary glands to be equally bright (a 1:1 brightness ratio).

Figure 1: Thyroid scan of a normal cat.  

Note that the salivary and thyroid glands are equally bright.

However, in a hyperthyroid cat, the adenoma cells take up far more of the tracer than the salivary glands do (see Figures 2 & 3).  Therefore, the adenomas show up far more brightly than the salivary glands.  This definitively diagnoses hyperthyroidism.  In order to diagnose hyperthyroidism in borderline cases, the specialist must use the software to carefully measure the densities of the thyroid and salivary glands.

Figure 2: Thyroid scan of a cat with unilateral right-sided thyroid adenoma.  

Note the brightness of the adenoma compared to the brightness of the salivary glands.

Figure 3: Thyroid scan of a cat with bilateral (two-sided) thyroid adenomas.  

Note the brightness of the adenomas compared to the brightness of the salivary glands.

Locating impalpable tumors
Impalpable tumors are fairly common in hyperthyroid cats; they affect about one-third of hyperthyroid cats.  These impalpable tumors come in two forms:  ectopic (not in the normal thyroid region) and large tumors that gravity pulls into the chest cavity.

Ectopic thyroid tissue is an embryological phenomenon that we see fairly often.  As the cells that develop into the thyroid gland traverse the embryo, they can leave traces of tissue anywhere from the base of the tongue to the base of the heart.   These traces can develop into functional thyroid tissue.  If these tissues develop a tumor, it will be impalpable, especially if the ectopic tumor is located on the tongue or in the chest cavity.  A thyroid scan can quickly and easily locate these tumors (see Figure 4).

Figure 4: Thyroid scan of a cat with an ectopic thyroid adenoma in the chest cavity. 

The veterinarian will not be able to palpate this tumor because of its location.

Like ectopic tumors, large tumors that descend into the chest cavity are impalpable.  We often see these tumors in cats that have been hyperthyroid for many months.  As the tumor grows progressively larger, gravity pulls progressively harder.  This causes the tumor to descend into the chest cavity.  Again, a thyroid scan swiftly detects these kinds of thyroid tumors (see Figure 5).

Figure 5: Thyroid scan of a cat with bilateral thyroid tumors. The left thyroid adenoma is small but should be palpable. The right thyroid tumor is very large and gravity has pulled it down into the thoracic cavity. The veterinarian would not be able to feel this tumor either.

Diagnosing thyroid carcinomas
As I discussed in a previous blog, some hyperthyroid cats have malignant thyroid carcinomas.  Neither palpation nor blood tests can determine whether a hyperthyroid cat has an adenoma or carcinoma.  Scintigraphy is extremely helpful in diagnosing invasive carcinomas.  On a scan, a carcinoma will appear as a large, irregularly shaped tumor extending beyond the limits of the normal thyroid region (see Figure 6).  We can also see whether the tumor has metastasized.

Figure 6: Thyroid scan of a cat with a thyroid carcinoma.  

Note that the tumor is irregularly shaped and is spreading into the chest cavity.

Diagnosing thyroid carcinomas is essential.  Without thyroid scintigraphy, a cat with a thyroid carcinoma would not receive the ultra-high dose of radioiodine necessary to destroy the cancer.

Calculating the radioiodine dose
In addition to diagnosing carcinomas (see above), thyroid scintigraphy helps us to make sure hyperthyroid cats receive the appropriate dose of radioiodine. Scintigraphy can precisely calculate the size of the tumor, even if it is impalpable.  With this information, we can calculate the dose of radioiodine for the cat, tailored specifically to that cat’s tumors.

Examples of recent thyroid scans
To see several examples of recent thyroid scans performed at our Bedford Hills facility, along with their accompanying interpretations, please visit our Nuclear Imaging Facebook page.