Diagnosing Cats with Borderline or Occult Hyperthyroidism

My patient is a 12-year-old, female, DSH that presented for hematuria. Routine blood work was normal but her serum T4 value was slightly high at 4.6 μg/dl (reference range, 1-4 μg/dl). Results of abdominal radiographs showed a bladder urolith which has resolved after 1 month of feeding a diet of Royal Canin Urinary SO.

The cat has been asymptomatic for hyperthyroidism and the serum T4 determination was only performed because of her age (we routinely screen all cats that are older than 10 years). She may be drinking more water but that is most likely due to the urinary SO diet).

On reexamination now, her weight is stable (5.3 kg), her body condition score is perfect, and she has a normal heart rate (200 bpm).  I did not palpate a thyroid nodule on this cat on either of my examinations. I repeated a serum T4 on this cat but now the value (3.1 μg/dl) is within the lab's reference range.

Do you think that this cat is hyperthyroid, or do we need a free T4 in this cat? Should I do any other testing?

My Response:

First of all, I agree with your protocol of starting to screen all senior cats for hyperthyroidism after the age of 10 years. Hyperthyroidism is a common disease, affecting about 10% of senior or geriatric cats (1). In the early stages of the disease, the owners (or their veterinarian) might not notice any clinical signs. Many of these cats are overweight, so loss of some body weight is commonly viewed as a "good" sign, rather than a problem. Screening allows us to pick up cats with mild or early hyperthyroidism before the disorder is allowed to progress to severe disease.

That said, we can never base a diagnosis of hyperthyroidism solely upon a single high T4 value. Lab error is not uncommon, and it's possible to see false-positive results. This is especially true today, when more and more commercial laboratories have stopped using the "gold standard" methods for T4 analysis (such as RIA or chemiluminence) and are switching to automated assays (homogenous enzyme immunoassays) that are run on the auto-analyzer together with the chemistry panel.

In this cat, a total T4 value of 3.1 μg/dl is in the upper third of the lab's reference range so it is still possible that the cat is suffering from mild hyperthyroidism. Fluctuations in circulating T4 and T3 in and out of the reference range is common in cats with mild hyperthyroidism, which can make diagnosis more difficult (2-6). The fact that a thyroid nodule cannot be palpated goes against the diagnosis of hyperthyroidism; however, tiny thyroid nodules can be very difficult to palpate.

So how do we handle cats like this?
We have a number of options, ranging from use of T3 suppression testing (7) to thyroid scintigraphy (8).  What I like to do as a first step in cats like this is to run a complete thyroid panel, which includes the following tests:

• serum T4 by RIA or chemiluminescence (Immulite)
• free T4 by equilibrium dialysis
• serum TSH (measured using the widely available canine TSH assay).

Cats with mild or occult hyperthyroidism will almost always have a low TSH value, at or below the limit of detection of the assay (<0.03 ng/ml) (4-6,9). The reason for this is based on endocrine physiology and the principle of pituitary negative feedback. In early hyperthyroidism, even very mild elevations in circulating T4 "feed-back" to the pituitary gland to shut off TSH secretion. However, the finding of undetectable TSH levels alone are NOT diagnostic for hyperthyroidism because 10-20% of normal cats will also have undetectable levels of TSH (9,10). That's why we have to look at the TSH level together with the total and free T4 values.

If the T4 is high-normal but the free T4 is high and TSH is undetectable, then hyperthyroidism is likely. However, if the total and free T4 are normal to borderline, and the serum TSH value is not suppressed, then hyperthyroidism is much less likely (4-6, 9).

You do have one other option, however, which is just to wait and recheck the cat in 1 to 3 months. In some cats, simply repeating the serum T4 concentration may be diagnostic if the T4 is fluctuating in and out of the reference range. In other cats with preclinical disease, it may take a number of weeks or even months for the serum total T4 concentrations to increase into the “high” range diagnostic for hyperthyroidism.

With time, however, all cats with mild hyperthyroidism will develop more severe disease as the thyroid tumor goes and secretes more T4, making it easier to diagnose (1). Mild or occult hyperthyroidism in a 12-year old cat is never an emergency. Sometimes close monitoring of body weight, heart rate, and thyroid size every few weeks to months is the best way to handle cats like this.

References:

1. Peterson M. Hyperthyroidism in cats: What's causing this epidemic of thyroid disease and can we prevent it? J Feline Med Surg 2012;14:804-818. 
2. Peterson ME. Diagnostic tests for hyperthyroidism in cats. Clin Tech Small Anim Pract 2006;21:2-9.
3. 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.
4. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association. 2012;92-110.
5. Baral RM, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;571-592.
6. 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.
7. Peterson ME, Graves TK, Gamble DA: Triiodothyronine (T3) suppression test: An aid in the diagnosis of mild hyperthyroidism in cats. J Vet Intern Med 1990;4:233-238.
8. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clin Tech Small Anim Pract 2006;21:10-16.
9. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. Can Vet J 2010;51:33-34.
10. Wakeling J, Moore K, Elliott J, et al. Diagnosis of hyperthyroidism in cats with mild chronic kidney disease. J Small Anim Pract 2008;49:287-294.

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