Thursday, July 14, 2011

Confirming the Diagnosis of Hyperthyroidism in Cats: Serum T4 Concentrations

Figure 1: Palpating a cat's neck
for a thyroid tumor
As I've discussed in my last few blood posts, we base our preliminary or initial diagnosis of hyperthyroidism on a combination of the three factors or findings:
  • Your cat's clinical features (e.g., weight loss despite a good appetite).
  • Your cat's physical examination findings (e.g., rapid heart rate, enlarged thyroid tumor).
  • The findings on routine laboratory testing (i.e., complete blood count, chemistry panel, and urinalysis).
If, after reviewing the cat's history and exam finding, we still believe that your cat has hyperthyroidism, the next step in the workup is to do specific tests to confirm the diagnosis of hyperthyroidism. This allows the veterinarian to properly treat your cat for the correct problem.

We have three different groups of tests that can be used to confirm as diagnosis of hyperthyroidism:
  • Basal or single blood tests, in which we measure one or more of the thyroid hormones themselves (e.g., T4 or T3), or the pituitary hormone called thyroid-stimulating hormone (TSH). As its name implied, TSH plays an important role in stimulating the thyroid gland to secrete the thyroid hormones.
  • Dynamic testing, in which 2 or more blood samples are collected before and hours-to-days after administration of a thyroid-stimulating or suppressive agent. These tests check the integrity of the pituitary-thyroid axis, which is malfunctioning in cats with hyperthyroidism.
  • Imaging techniques such as thyroid scintigraphy provide a visual display of the structure and function of the thyroid gland. This is considered by most to be the “gold standard” diagnostic test since thyroid scanning will allow the diagnosis of hyperthyroidism before laboratory tests are abnormal. Thyroid scanning can also exclude a misdiagnosis of hyperthyroidism in cats with false thyroid hormone elevations.
In this first blog post in this series of “Confirming the Diagnosis of Hyperthyroidism in Cats,” I'm going to discuss the use of serum thyroxine (T4)  concentrations to make a definitive diagnosis of hyperthyroidism in cats.

In my next posts, we will discuss the use of free T4, then look at the use of serum TSH measurements. I will then turn to when we do dynamic thyroid function testing. Finally, I’d end this section on diagnostic testing with a post on the value of thyroid scintigraphy (thyroid nuclear imaging or scanning) in the diagnosis of hyperthyroidism.

How the Thyroid Works —Production of Its Hormones

Figure 2: T4 with its
 four iodine groups
A unique role of the thyroid gland is to take iodine supplied in food and use it to produce the 2 major thyroid hormones, thyroxine (tetraiodothyronine or T4) and triiodothyronine (T3). Important components of both the T4 and T3 molecules include the amino acid tyrosine and iodine (see Figure 2).

Inside the thyroid gland, T4 and T4 are bound to a large storage protein called thyroglobulin. When the body requires thyroid hormone, the thyroid gland releases stored T4 and T3 into circulation. T4 makes up nearly 90% of the circulating thyroid hormones, while T3 makes up less than 10%.

Because thyroid hormone synthesis requires iodine, either a deficiency or an excess of iodine can profoundly affect thyroid function, and promote autoimmune thyroiditis.

Measuring the Serum Thyroxine (T4) Concentration

The test to measures the total amount of T4 in your cat’s blood should always be the first diagnostic test used if hyperthyroidism is suspected.

The finding of a high serum T4 concentration is the hallmark of hyperthyroidism. As a diagnostic test for hyperthyroidism, the total T4 is a highly specific test. Falsely high T4 values (false-positive test results) generally are not seen unless overt laboratory errors in measurement are responsible, and that is extremely rare. Methods for T4 measurement are readily accessible, relatively cheap, and only require a small blood sample.

Figure 3: Box plots of total T4 concentrations in normal cats, hyperthyroid cats, and cats with nonthyroidal disease. The T-bars represent the main body of data. The box represents the interquartile range (25th percentile to 75th percentile range or the middle half of the data). The horizontal bar in the box is the median. Outlying data points are represented by open circles. The shaded area indicates the reference interval (normal range). From reference 9.

Serum total T4 is a great screening test for hyperthyroidism. The total T4 assay has a test sensitivity of over 90%; in other words, 90% of all hyperthyroid cats can be diagnosed by measuring a T4 concentration (Figure 3, above).

However, this means that approximately 10% of cats with hyperthyroid will have serum total T4 concentration that are not high but remain within the normal, reference range limits. When “normal” T4 values are found, they are usually within the high-normal range.

Thus, a high total T4 value is diagnostic for hyperthyroidism in cats, especially if you suspect hyperthyroidism based upon the cat’s clinical features and physical exam findings. However, if hyperthyroidism is suspected but the serum T4 test is normal, it is still possible you’re your cat has the disease.

What how can the serum T4 be normal if a cat is hyperthyroid?

There are 2 main reasons or situations where this can occur:
  1. In early or mildly affected hyperthyroid cats, serum total T4 concentrations can fluctuate in and out of the reference range. Such fluctuation occurs in all hyperthyroid cats, but the degree of fluctuation is of little diagnostic significance in cats with moderate to advanced hyperthyroidism and markedly high T4 concentrations.
  2. Other illness or disease (not related to hyperthyroidism) is capable of suppressing serum total T4 from high concentrations to within the mid- to high-end of the reference range. Concurrent hyperthyroidism should always be suspected in severely ill cats with mid to high reference range serum total T4 concentrations.
What do we do if the serum T4 is normal and hyperthyroidism is still suspected?

In most cats with early or mildly hyperthyroidism, serum total T4 concentrations will eventually increase into the diagnostic hyperthyroid range with time. So one approach to cats like this is to simply wait and retest a few weeks later.

Similarly, after a hyperthyroid cat recovers from the nonthyroidal illness, the serum T4 values will again increase in the high range, confirming the diagnosis. So concurrent disease should always be excluded in any cat suspected of having hyperthyroidism when the serum T4 concentration is normal.

With time, almost all hyperthyroid cats will eventually develop high T4 concentrations.

Other diagnostic tests may also be used provide a means of diagnosing hyperthyroidism in cats that have a normal T4 test. These options include measurement of free T4, TSH, dynamic thyroid function testing, or thyroid scintigraphy (all discussed in my next upcoming blog posts).

  1. Baral R, Peterson ME: Thyroid Diseases, In: Little, S. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders, in press.
  2. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clinical Techniques in Small Animal Practice 2006;21:10-16.
  3. Graves TK, Peterson ME. Diagnostic tests for feline hyperthyroidism. The Veterinary Clinics of North America: Small Animal Practice 1994;24:567-576.
  4. Kintzer PP, Peterson ME. Nuclear medicine of the thyroid gland. Scintigraphy and radioiodine therapy. The Veterinary Clinics of North America: Small Animal Practice 1994;24:587-605.
  5. Peterson ME, Graves TK, Cavanagh I. Serum thyroid hormone concentrations fluctuate in cats with hyperthyroidism. Journal of Veterinary Internal Medicine 1987;1:142-146.
  6. Peterson ME, Graves TK, Gamble DA. Triiodothyronine (T3) suppression test. An aid in the diagnosis of mild hyperthyroidism in cats. Journal of Veterinary Internal Medicine 1990;4:233-238.
  7. Peterson ME, Gamble DA. Effect of nonthyroidal illness on serum thyroxine concentrations in cats: 494 cases (1988). Journal of the American Veterinary Medical Association 1990;197:1203-1208.
  8. 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.
  9. 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. Journal of the American Veterinary Medical Association 2001;218:529-536.
  10. Peterson ME. Diagnostic tests for hyperthyroidism in cats. Clinical Techniques in Small Animal Practice 2006;21:2-9.
  11. 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
  12. Peterson ME: Hyperthyroidism in cats, In: Rand, J (ed), Clinical Endocrinology of Companion Animals. New York, Wiley-Blackwell, in press.

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