Issue Ninety-Six – December 2015
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CLINICAL CASE MANAGEMENT NEWSLETTER
The Calgary Animal Referral & Emergency Centre Animal Hospital
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Issue Ninety-Six – December 2015
Feline Hyperthyroidism
Dr. Cheryl Vargo DVM, MVetSc, DACVIM
When I first started out in general practice right after graduation, I have to admit, I think I loved
hyperthyroidism because I thought it was easy. You have an old cat with a big honking thyroid,
measure a total T4 (TT4) and BOOM! Place it on methimazole or send it for radioactive iodine and
call it a day. Fast forward 16 yrs, I would say now I love hyperthyroidism because of the challenges
it poses both in diagnosis and treatment.
When a senior cat comes in with classical signs of PU/PD, vomiting, diarrhea, losing weight despite
a good appetite, etc., hyperthyroidism is on everyone’s differential list. Add to the fact that a TT4 is
on most if not all senior blood panels, and one would think the diagnosis should be straightforward.
However, how does one interpret the cat with a high TT4 but no real clinical signs, or a cat with
clinical signs that has a TT4 in the mid normal reference range?
I think we were all taught that hyperthyroidism is an old cat’s disease. And that’s mainly true, less than
5% of hyperthyroid cats are diagnosed younger than 8 years of age.1 While the mean is reported
to be 13 years, I now think when I first started out, I may have missed some hyperthyroid cats initially
because even though I palpated a thyroid slip, I don’t think I checked their TT4’s until they were at
least 10 years old.
When I was in Chicago I had my first case of apathetic hyperthyroidism. Tuffy was an 11 yr old MN
DSH that had a history of inappetance, weight loss and lethargy. He had a palpable thyroid nodule
and on blood work there were elevated liver values, elevated bilirubin, mild hypoalbuminemia
and an elevated TT4. The owners declined further workup so he was sent home on supportive
medication (mirtazapine, denosyl, pepcid) and methimazole. Three weeks later, he was eating dry
food well, his blood abnormalities had normalized and his TT4 had come down considerably. Less
than 10% of hyperthyroid cats will be apathetic and often these cats will have concurrent neoplasia
or congestive heart failure.2
Serum TT4 with it’s high sensitivity and specificity (both around 90-95%), is our best initial screening test
for hyperthyroidism. Having said that, 5-10% of all hyperthyroid cats and 20-40% of cats with early
or mild hyperthyroidism will have a TT4 within the reference range.3 Thus finding a normal TT4 does
not preclude a diagnosis of hyperthyroidism. Options in a cat that you suspect has hyperthyroidism
with a normal TT4 would include retesting in 3-6 weeks, running a serum free T4 (fT4) vs a fT4 and TSH.
The serum fT4 has a higher test sensitivity than TT4 (95-98%), but it has a lower specificity (75-85%).3 This
means that up to 25% of cats with an elevated fT4 will in fact be euthyroid. This is important because
it tells us that the fT4 test should never be used alone to confirm a diagnosis of hyperthyroidism.
I hadn’t really thought about using serum TSH in the diagnosis of hyperthyroidism, after all a felinespecific TSH assay still needs to be developed. Yet there was a recent paper that showed that serum
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TSH concentrations (using a validated canine TSH assay) were suppressed in 98% of hyperthyroid cats.4
The value in using TSH would be in helping to make a diagnosis of early hyperthyroidism, ie. you have
a high normal TT4 with a high fT4 and if the TSH concentration is suppressed, you have your diagnosis
vs if the TSH is not suppressed, then you need to re-evaluate or consider thyroid scintigraphy which is
the gold standard but is not readily available. In cats with mild or early hyperthyroidism whether to
start treatment I think depends on their clinical signs and if you can palpate a thyroid nodule. If they
are asymptomatic I would consider waiting and rechecking in a month. As I don’t believe we have
any evidence right now to say mild cases of hyperthyroidism cause harm in the short term and we
know our treatments have side effects, it becomes for me weighing risk over benefit.
Although uncommon, there have been reports of cats with falsely high TT4 values. In a cat that lacks
clinical signs or a palpable thyroid, repeating the TT4 level or performing further thyroid function tests
would be indicated. It is important to remember that hyperthyroidism is a clinical diagnosis, ie. lab
results need to be combined with the cat’s clinical signs and the presence of a palpable thyroid
nodule to make the diagnosis.
The treatments available for feline hyperthyroidism include methimazole, radioactive iodine,
dietary (Hills y/d) and surgery. I list surgery last for a reason, unless the cat is both fractious at home
and in the clinic, my own belief is that radioactive iodine is both safer (no anesthesia or risk for
hypoparathyroidism, recurrent laryngeal nerve damage), easier (one time SQ administration) and
more permanent than surgery (will tx ectopic tissue).
It makes sense that hyperthyroid cats with pre-existing azotemia (5-10%) will have a worse prognosis
than do cats that are not azotemic prior to treatment for hyperthyroidism.5 Since we can predict
that the glomerular filtration rate (GFR) will fall once euthyroidism is restored, starting with a low
dose (ex. 1.25 mg orally once daily) of methimazole with gradual dose escalation and monitoring
along with concurrent management of chronic kidney disease (CKD) is prudent before considering
a more definitive treatment in these cats.
What is more challenging is trying to predict which hyperthyroid cats will become azotemic within
6 months of starting treatment; estimations range from 15-49% depending on therapeutic modality
(note: do not have a % for diet).5,6 The determination of GFR is clearly the best predictor of posttreatment CKD, with a low to low normal GFR indicating that a hyperthyroid cat is at increased risk for
post-treatment azotemia.5 However, techniques for assessment of GFR are often not practical and
not used in general practice. I could see potential in the use of the new symmetric dimethylarginine
(SDMA) test (ie. have baseline and then monitor for increases with treatment), however, I am not
aware of anyone having looked into or published for this purpose. Despite their limitations, BUN,
creatinine and USG are the best that we have at this time. And thus it begs the question, should
methimazole trials be performed in all hyperthyroid cats as it can provide a preview of sorts of how
the cat will be after curing the hyperthyroidism. I used to do that a lot but now it’s rare, unless the
cat has advanced CKD. It has been shown that the development of azotemia in hyperthyroid cats
following treatment does not negatively affect their survival. In one study, the medium survival time
of cats that developed azotemia (595 days) was similar to that in cats that remained non-azotemic
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(584 days) after treatment.7 In most cats that develop post-treatment azotemia, the CKD is not
that severe, ie. would be unusual to see a jump of more than one IRIS stage after treatment. And
the decline in GFR after successful treatment tends not to be very progressive.5 In other words, if a
hyperthyroid cat is to become azotemic, we would expect to see that develop within 1 month of
treatment but then remain relatively stable over many months. It is also important to remember that
if methimazole is used as a long term treatment for hyperthyroidism, it does nothing for the thyroid
tumor in of itself, ie. it keeps growing. This means that often the dose of methimazole will need
to be increased over time and there has been speculation that transformation of benign thyroid
adenoma/hyperplasia into malignant carcinoma can occur.8.9
I can say that I have very limited experience with feeding Hills y/d to hyperthyroid cats. I have had
one owner who was feeding y/d but then would add fancy feast to it in order to get the cat to eat
it (thus nullifying any benefit of course), and one cat who was being managed on y/d because he
had developed facial pruritus on methimazole. A recent paper that looked at feeding Hills y/d to
hyperthyroid cats, showed that 83% (39/47 cats) had a normal total T4 by 180 days, however, clinical
improvement in body weight and heart rate were not observed.9 The long term consequences of
feeding such a diet is unknown. In addition, I don’t think as of yet, we have a clear indication of
how long cats should be off this diet should the owners wish to pursue radioactive iodine treatment;
in one study 2 weeks was suggested.10
Avoiding iatrogenic hypothyroidism is critical in our hyperthyroid patients. It has been shown
that in dogs and humans, hypothyroidism reduces GFR and this is also seems to be true for cats.
Causing hypothyroidism in a hyperthyroid cat contributes to the development of azotemia and
shortens survival. This is demonstrated in a study where cats with iatrogenic hypothyroidism were
more likely to develop azotemia in the 6 months after treatment of hyperthyroidism than cats that
remained euthyroid. Hypothyroid cats with azotemia also had shorter survival times (456 days) than
nonazotemic cats (905 days), whereas no difference in survival between euthyroid cats with or without
azotemia could be detected.11 Although there is not a feline-specific TSH assay, the commercially
available canine TSH assay cross-reacts with feline TSH enough to enable it’s use as a diagnostic
test for hypothyroid cats. I was surprised to learn that in one study, iatrogenic hypothyroidism (low
TT4, elevated TSH) was 20% in hyperthyroid cats receiving methimazole, and that the median dose
for cats with a TT4 below the reference range was 7.5 mg/cat/day (range, 5-15).6 This suggests
that we need to continue to initially dose methimazole conservatively (I go 2.5 mg BID), and if the
TT4 is in the lower half of the reference range we should consider measuring TSH, especially if they
become azotemic. If the TSH is elevated, I would lower the dose and reassess. For cats that develop
iatrogenic hypothyroidism and are azotemic, most will show improvement in their azotemia as the
hypothyroidism resolves and euthyroidism is restored.5,6 For cats that have undergone radioactive
iodine treatment, the recommendation is to wait 3 months before making a diagnosis of iatrogenic
hypothyroidism.12 L-thyroxine at a low dose (0.1 mg twice daily) can be administered with dose
adjustments based on post-pill TT4 and TSH measurements.5
Hyperthyroidism is commonly diagnosed in our senior feline patients. Being aware of the challenges
in diagnosis and treatment of hyperthyroidism is paramount to success.
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References:
1.
Scott-Moncrieff JC. Feline Hyperthyroidism, In: Feldman EC, Nelson RW, Reusch CE, Scott-Moncrieff JC, eds, Canine & Feline
Endocrinology (4th Ed). St. Louis, Missouri: Elsevier Saunders, 2015:136-195.
2.
Mooney CT, Peterson ME. Feline Hyperthyroidism, In: Mooney CT, Peterson ME, eds, Manual of Canine and Feline Endocrinology (4th
Ed). Quedgeley, Gloucester, British Small Animal Veterinary Association, 2012:92-110.
3.
Peterson ME. Diagnosis of Hyperthyroidism: A Critical Evaluation of our Current Available Tests. ACVIM SAIM Endocrinology Course
March 2015.
4.
Peterson ME, Guterl JN, et al. Evaluation of Serum Thyroid-Stimulating Hormone Concentration as a Diagnostic Test for Hyperthyroidism
in Cats. J Vet intern Med 2015;29:1327-1334.
5.
Peterson ME. Treatment of Hyperthyroidism and Concurrent Renal Disease. ACVIM SAIM Endocrinology Course October 2010.
6.
Aldridge C, Behrend EN. et al. Evaluation of Thyroid-Stimulating Hormone, Total Thyroxine, and Free Thyroxine Concentrations in
Hyperthyroid Cats Receiving Methimazole Treatment. J Vet Intern Med 2015;29:862-868.
7.
Wakeling J, Rob C, et al. Survival of Hyperthyroid Cats is Not Affected by Post-Treatment Azotemia. J Vet Intern Med 2006;20:1523.
8.
Peterson ME. Treatment of Thyroid Carcinoma in Cats. ACVIM SAIM Endocrinology Course October 2010.
9.
Hui, TY, Bruyette DS, et al. Effect of Feeding an Iodine-Restricted Diet in Cats with Spontaneous Hyperthyroidism. J Vet Intern Med
2015;29:1063-1068.
10. Scott-Moncrieff, JC, Heng HG, et al. Effect of a Limited Iodine Diet on Iodine Uptake by Thyroid Glands in Hyperthyroid Cats. J Vet
Intern Med 2015;29:1322-1326.
11. 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;24:1086-1092.
12.
Peterson ME. Approach to Discordant Test Results in Cats. ACVIM SAIM Endocrinology Course October 2010.
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