Confirming the Diagnosis of Hyperthyroidism in Cats: Serum T3 Concentrations

As I discussed in my last post, the feline thyroid gland makes two active thyroid hormones, thyroxine (T4) and triiodothyronine (T3). T4 makes up nearly 90% of the circulating thyroid hormones, while T3 makes up less than 10%.

Although only 10% of the hormone produced in the thyroid gland is T3, this thyroid hormone is three to ten times more active than T4. In order for the body’s cells and tissues to use more of this active form of thyroid hormone, T4 (which contains four iodine molecules) is converted to T3 or (which contains three iodine molecules) by losing an iodine molecule. In cats, this function is performed in the liver and kidney by deiodinase enzymes that act to remove an iodine group from the thyroid hormone molecule (1).

The deiodination of T4 to T3, reverse T3, and other iodothyronines is an integral component of thyroid hormone metabolism. This deiodination, depending on whether it occurs at the outer or inner rings of the T4 molecule, serves to either activate or inactivate this hormone (see Figure above). Again, T3 is the most active thyroid hormone, whereas reverse T3 (rT3) is considered to be metabolically inactive.

There are 3 different thyroid deiodioinase enzymes:

• Iodothyronine deiodinase type I (IDI) is commonly found in the liver and kidney. It is also present in the thyroid of many species including dogs and humans, but IDI is not present in the feline thyroid gland (1).
• The type II enzyme (IDII) in skeletal muscle and thyroid gland (but again, cats do not appear to have IDII in their thyroid gland).
• Type III (IDIII) is found in the fetal tissue and brain matter.

IDII can only deiodinate the outer ring of T4 or rT3. IDIII can only deiodinate the inner ring of T4 or T3. IDI can deiodinate both the outer and inner rings.

But the real question is this: If T3 is three to ten times more active than T4, shouldn’t we be measuring serum T3 to better diagnose hyperthyroidism in cats?

Measuring the Serum Triiodothyronine (T3) Concentration

Although T3 is the important thyroid hormone for regulation of a cat's metabolic state, this hormone reflects tissue thyroid activity. Unfortunately, measuring the serum levels of T3 are a poor reflection of what is happening in the tissues.

Compared to the serum T4,  measuring the serum T3 concentration is much less useful as a diagnostic test for hyperthyroidism (2-7). Over 30% of hyperthyroid cats have normal circulating T3 concentrations (See Figure, below).

Box plots of total T3 concentrations in 172 clinically normal cats, 917 cats with hyperthyroidism, and 221 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 3.

None of the cats with high serum T3 values have normal serum T4 concentrations, so measuring T3 test does not provide any additional information not gained from measuring T4 alone.

Bottom line: Measuring total T3 alone is not recommended for investigation of hyperthyroidism in cats.

The reason for this is unknown, but based on studies of normal cats (1), it is likely that most of the circulating T3 in these hyperthyroid cats comes from conversion from T4 in peripheral tissues, and is not secreted directly by the thyroid tumor.  That could explain why measurement of T4 is a better diagnostic test for hyperthyroidism than is T3.

In my next posts, we will discuss the use of free T4, then look at the use of serum TSH measurements. 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.

References:

1. Foster DJ, Thoday KL, Beckett GJ. Thyroid hormone deiodination in the domestic cat. Journal of Molecular Endocrinology 2000;24:119-126.
2. Baral R, Peterson ME: Thyroid Diseases, In: Little, S. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders, in press.
3. Graves TK, Peterson ME. Diagnostic tests for feline hyperthyroidism. The Veterinary Clinics of North America: Small Animal Practice 1994;24:567-576.
4. 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.
5. Peterson ME. Diagnostic tests for hyperthyroidism in cats. Clinical Techniques in Small Animal Practice 2006;21:2-9.
6. 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
7. Peterson ME: Hyperthyroidism in cats, In: Rand, J (ed), Clinical Endocrinology of Companion Animals. New York, Wiley-Blackwell, in press.