Feline iatrogenic hypothyroidism

Geriatric cats are prone to hyperthyroidism and chronic renal disease (CRD). Because thyroid function can influence renal function, it's not surprising that these conditions frequently coexist. Hyperthyroidism can, in fact, mask CRD because of the impact of this disease on cardiovascular function. There are general increases in cardiac output (higher heart rates, increased contractility) and peripheral vasodilation (increased metabolic demand resulting in the release of vasodilators) that lead to an increase in renal blood flow and glomerular filtration rate.

With treatment of the hyperthyroid state, these effects are lost, which can cause an increase in renal values on blood work. In one study, about 15 percent of hyperthyroid cats that had normal renal values became azotemic within 240 days of treatment.1 In cats that are azotemic before treatment, the CRD can worsen substantially.

Treatment for hyperthyroidism can occasionally lead to a hypothyroid state that may or may not be clinical. This is most common with bilateral thyroidectomy (100 percent) and radioactive iodine (75 percent) and is much rarer with methimazole treatment (35 percent).2

Past research finds cause and effect

One study found that hypothyroidism resulted in a shorter lifespan in cats treated for hyperthyroidism.3 This study had two portions: to follow 12 cats that were treated with radioactive iodine to see if they became hypothyroid, and to look at a separate group of cats six months after treatment for hyperthyroidism to see if there was a relationship between thyroid status and the development of azotemia.

GETTY IMAGES

Of the 12 cats treated with radioactive iodine, 10 became hypothyroid, as diagnosed via an elevated thyroid-stimulating hormone (TSH) concentration. In the survival portion of the study, 51 percent of the 80 cats evaluated had a total thyroxine (T4) concentration below the reference interval. Of these cats, 68 percent had a TSH concentration above the reference range, classifying them as hypothyroid. Five cats had normal T4 but high TSH concentrations, which excluded them from the analysis.

Hypothyroid cats had lower heart rates, lower packed cell volumes and lower alkaline phosphatase (ALP) activity than euthyroid cats. There was no difference in survival times between the euthyroid and hypothyroid groups. However, 57 percent of hypothyroid and only 30 percent of euthyroid cats developed azotemia after treatment, which was statistically significantly different. The survival for azotemic hypothyroid cats was also significantly shorter (a median of 456 days) than that of nonazotemic hypothyroid cats (a median of 905 days) and euthyroid cats (a median of 794 days).

This study suggests that cats treated for hyperthyroidism that are azotemic and hypothyroid may be at greater risk of a poorer outcome. Additional thyroid function testing such as a TSH concentration to assess for subclinical hypothyroidism may be a consideration. The assay used in this study was a commonly used canine assay (Immulite Canine TSH assay—Diagnostic Products Corporation) since a feline assay is not widely available. Check with your laboratory for additional information on this type of testing.

Reversing the effects

At the 2012 ACVIM Forum in New Orleans, the Royal Veterinary College in London presented a research abstract on the impact of restoring euthyroidism on renal function in cats made iatrogenically hypothyroid.4 Cats were selected that had a T4 concentration below the reference interval and an elevated TSH concentration. These cats were being treated medically, so doctors reduced their hyperthyroid medications to establish euthyroidism.

A total of 12 cats were included in the study. Of these 12, nine were azotemic. Once euthyroidism was established, creatinine concentrations dropped significantly and azotemia resolved in three of the nine cats. Other statistically significant changes included an increase in ALP activity and heart rate with a decrease in body weight. This study did not address if there was any survival benefit to this dosage adjustment, though it would be expected.

Implications for practice

Previously we were only concerned about iatrogenic hypothyroidism in treated hyperthyroid cats when this was clinically overt. Usually we made the diagnosis when clinical signs, such as lethargy and heat seeking, were present and concerning to the owner.

The research carried out over the last few years suggests that iatrogenic hypothyroidism is not as innocuous as we thought, at least in cats that have CRD. In this scenario, hypothyroidism contributes to shorter survival. Making them euthyroid improves their azotemia and hopefully lengthens their survival time. As a result, if you have an azotemic hyperthyroid cat that is being treated medically, adjust the drug dosage to prevent hypothyroidism.

As it is, iatrogenic hypothyroidism is much less common in medically treated cats. If treatment was via bilateral thyroidectomy or radioactive iodine treatment, the chances are good (probably > 80 percent) that the cat does have iatrogenic hypothyroidism.

We have yet to examine if thyroid supplementation should be considered in these cats, though it does appear tempting. Of course, in some cases, the reason the cat was treated with surgery or radioactive iodine was to avoid administering oral medication to the cat, so that would make for an interesting conversation with the owner.

Anthony Carr, Dr. med. vet., DACVIM, is a professor of small animal clinical sciences at the Western College of Veterinary Medicine in Saskatoon, Canada.

References

1. Williams TL, Peak KJ, Brodbelt D, et al. Survival and the development of azotemia after treatment of hyperthyroid cats. J Vet Intern Med 2010;24(4):863-869.

2. Graham PA, Refsal KR, Nachreiner RF, et al. Measurement of feline thyrotropin (TSH) using a commercial canine immunoradiometric assay. J Vet Intern Med 2000;14:342.

3. 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(5):1086-1092.

4. Williams TL, Elliot J, Syme H. Restoration of euthyroidism in medically treated hyperthyroid cats with iatrogenic hypothyroidism (IH) improves renal function, in Proceedings. Am Coll Vet Intern Med 2012;753-754.