Q & A: Hypothyroidism in a Cat Treated with Radioiodine (I-131)

I have a question about Mischief, a 13-year-old female spayed DSH cat, who was treated 3 years ago for hyperthyroidism with radioiodine (I-131).

At her first recheck 1-month after treatment, her serum T4 concentration was low-normal at 1.0 μg/dl (reference range, 0.5-4.5 μg/dl). In the months and years since that time, the serum T4 values have continued to be slightly low. On her annual exam a year ago, the T4 was low at 0.4 μg/dl.

This year she had gained a great deal of weight (she now weighs 7 kg) and has a body condition score of 4/5. The owners have noticed increasing more dandruff and shedding, and they were worried that she was becoming hypothyroid. I rechecked her serum T4 concentration, which was still low at 0.4 μg/dl.

I know that cat can develop iatrogenic hypothyroid after radioiodine treatment. To help rule out hypothyroidism, I had the lab measure a serum TSH on the same sample (since there isn’t a feline TSH assay, the lab used the canine-specific TSH assay). The cTSH level was 8.29, which seems very high, at least based on the reference range limits for cTSH in dogs (0.05 - 0.42 ng/ml).

My plan is to start l-thyroxine supplementation and monitor signs. However, I have two questions:

1. I don't have reference values for feline TSH, so I was hoping for some confirmation that this cat’s TSH value is indeed high.
2. What dose of L-T4 should I use?

My Response:

It's very uncommon for hypothyroidism to develop clinically this long after treatment with radioiodine. Generally, the serum T4 values in cats with iatrogenic hypothyroidism are already low by 1 month after I-131 treatment and stay low thereafter. And most of these hypothyroid cats become quite symptomatic by 3 to 6 months, not 3 years (1-3).

That said, the cTSH value in this cat is high and that would be consistent with primary hypothyroidism (3,4).  A good reference range has not been established for  serum cTSH in cats, but I like to see the values rise above 1.0 ng/ml before I say it's definitely elevated.

Before you start treatment, I would definitely do all that you can to rule out nonthyroidal illness, inasmuch as this is a well-known reason for low serum T4 values in cats (5, 6).

Although the canine TSH assay appears to work fairly well in some cats with apparent hypothyroidism (4), sometimes the results just don't make a whole lot of sense. For example, I've had a couple cats now on replacement doses of L-T4 as high as 0.3-0.4 mg per day that failed to normalize their cTSH level, despite serum T4 values that were in the high-normal to slightly high range.

By definition, a high circulating T4 should suppress the TSH level to non-detectable levels. So what's going on here? We still don't know, but it may be the assay. Hopefully, the development of a feline TSH assay will solve these issues.

We also don't know how nonthyroidal illness affects the cTSH levels but we do certainly know that any illness will lower the total T4 into the subnormal range. So this cat could be suffering from any number of other diseases, such as renal, liver, or GI disease (4,5).

Have you done a routine blood and urine testing (eg, CBC, serum chemistry panel, and urinalysis)? If not, I'd certainly do that, together with a free T4, before you start L-T4 supplementation. Many hypothyroid cats will develop mild anemia and hypercholesterolemia, similar to what we see in dogs that are hypothyroid (1-3).

If you do decide to supplement, start with a dose of 0.1 mg once daily or divided. It's quite safe to increase to 0.1 mg BID, if needed. I know that this sounds high, but remember that a cat is NOT a dog!

There is much to learn about thyroid hormone supplementation in cats. I give the medication on an empty stomach if possible, based on the fact that the absorption of L-T4 is better in both humans and dogs when given this way. I follow post-pill T4 values (4-6 hours) and cTSH levels, but again, no one knows when the best time is to recheck these cats.

References:

1. Peterson ME: Feline hypothyroidism, In: Kirk RW (ed): Current Veterinary Therapy X. Philadelphia, WB Saunders Co., pp 1000-1001, 1989
2. Greco DS. Diagnosis of congenital and adult-onset hypothyroidism in cats. Clin Tech Small Anim Pract 2006;21:40-44.
3. Daminet S. Feline hypothyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Small Animal Endocrinology. 4th ed. Shurdington, Cheltenham: British Small Animal Veterinary Association, 2010.
4. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. Can Vet J 2010;51:33-34.
5. Peterson ME, Gamble, DA: Effect of nonthyroidal disease on serum thyroxine concentrations in cats: 494 cases (1988). Journal of the American Veterinary Medical Association 197:1203-1208, 1990
6. Peterson ME, Melián C, Nichols CE: 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 218: 529-536, 2001

More information:

I just came across a recent study which studied the absorptive kinetics of L-thyroxine in young, healthy cats (La Traon, et al, 2009). In that abstact reported at the ECVIM meeting in 2009, normal cats were given a single oral dose of L-T4 (Leventa solution, Merke Animal Health, 1 mg/ml) as a single dose (0.1 mg per cat) after an overnight fast, with food withheld for an additional 8 hours after the L-T4 administration.

The L-T4 was rapidly absorbed in these cats, reaching a mean peak concentration of around 5 μg/dl at 2-4 hours after administration. The L-T4 was also rapidly cleared in these cats, with an apparent serum half-life of 5.5 hours. This is shorter than the half -life reported for healthy dogs after administration of the same liquid formulation. Despite the short half-life, serum T4 value at 24 hours post-pill were generally higher than pre-pill concentrations, suggesting that once daily supplementation may be adequate in cats.

Although this study of the L-T4 absorption in normal cats helps us, we aren't treating clinically normal cats with a single oral dose after an overnight fast — rather, we are chronically treating hypothyroid cats that are generally older, sometimes with other concurrent diseases.  So we still don't really yet know the best dose or timing for post-pill T4 testing in cats with hypothyroidism.

Reference:

1. Le Traon G, Burgaud S, Horspool L. Pharmacokinetics of L-thyroxine after oral administration to healthy cats. Proceedings of the 19th ECVIM-CA Congress (European College of  Veterinary Internal Medicine - Companion Animals). p. 269, 2009.