18 Aug 2008
Jennifer Wakeling
Job Title
JENNIFER WAKELING describes the management of this condition and the importance of regularly weighing patients
HYPERTHYROIDISM is a very common disease in elderly cats, with a mean age of onset around 13 years.
But how common is it? I estimated the annual incidence (new cases per year) of hyperthyroidism at a London first opinion clinic, which sees a high proportion of sick cats, to be around 10 per cent of all cats aged more than nine years old1.
Data provided by Pet Protect UK gave an estimated annual incidence of hyperthyroidism of 2.5 per cent in its insured older cat population.
Put another way, this means that between one-in-10 and one-in-40 cats aged more than nine years presented for a consultation should be newly diagnosed with hyperthyroidism each year, with the exact proportion probably dependent on the proportion of sick cats in the waiting room. So, if practitioners see a lot of older cats, they should be seeing a lot of hyperthyroidism.
There is little concrete information regarding the underlying cause of feline hyperthyroidism. It is well known that the pathology underlying it is benign hyperplastic or adenomatous nodules () in the thyroid, which produces thyroxine independent of thyroid-stimulating hormone (TSH) control2, 3. Careful study of these nodules has shown many of them to have activating mutations of the TSH receptor4. However, the causes of these mutations are unknown and are likely to be multifactorial.
Pure-bred cats, especially Siamese, are less likely to be diagnosed with hyperthyroidism5, 6, so there is probably a genetic susceptibility to the disease in domestic cats. Questionnaire studies have shown an association between hyperthyroidism and canned food, especially if the diet is made up of more than 50 per cent canned food5–9. However, it is not known whether it is the can itself or the food that is the problem.
Hyperthyroidism causes a variety of changes that, in the most advanced form of the disease, usually lead to the characteristic picture of an emaciated cat with a ravenous appetite that is restless and/or aggressive and may exhibit vomiting, diarrhoea, goitre, murmur and tachycardia.
However, these changes are usually only seen with a marked elevation of thyroxine, and mild disease may cause only subtle weight loss that might not be discerned by the owner.
This is one of the reasons why it is incredibly important to weigh cats every time they visit the clinic, because this way a veterinarian can probably pick up the weight loss before the owner does. I have often picked up mild hyperthyroidism on a senior cat health screen during an annual wellness examination (otherwise known as the yearly vaccine appointment) in a cat that the owner perceived to be healthy, but that had some mild weight loss over the preceding year. Some hyperthyroid cats may show an “apathetic” form of the disease that presents with anorexia, rather than polyphagia. Some cats with hyperthyroidism may show excessive grooming, as opposed to the classic unkempt appearance of a hyperthyroid cat. Therefore, it is also a good idea to do a thyroid check in an older cat presented for selfinduced alopecia.
Cats have a low TSH concentration (below the limit of quantification of the assay – less than 0.03ng/ml) at the diagnosis of hyperthyroidism and also for one to three years prior to this12, 13. Euthyroid senior cats with low TSH were also shown to be more likely to have thyroid nodular change14 than euthyroid senior cats with measurable TSH. A prospective study has shown that older euthyroid cats with a TSH of less than 0.03ng/ml had an approximately one-in-three chance of becoming hyperthyroid within a year, even if their total thyroxine concentration (tT4) was initially well within the reference range (less than 30nmol/l)13. The euthyroid cats with low TSH that subsequently became clinically and biochemically hyperthyroid could be considered to be subclinically hyperthyroid.
Hyperthyroidism is generally considered to be a disease that is easy to diagnose, on the basis of an elevated tT4.
Hyperthyroidism commonly causes elevated liver enzymes; therefore, the presence of raised alanine aminotransferase (ALT) or alkaline phosphatase (ALKP) in a senior cat should be a flag to recommend the measurement of tT4. However, as the ability to diagnose hyperthyroidism has improved, more cats are seen in the early stages of the disease (when tT4 may still be in the reference range), especially if there is concurrent disease that can cause suppression of thyroid hormones. It is desirable to diagnose hyperthyroidism early, as there is evidence in humans that even subclinical hyperthyroidism can have a deleterious effect on the circulatory system15, 16 and bone density17. Hyperthyroidism has been associated with increased urine protein to creatinine ratios (UPC), and high UPCs are associated with a decreased survival rate in cats with hypertension and chronic kidney disease (CKD)18–21.
The reference range for tT4 in cats should not be regarded as set in stone. The upper limit of different laboratory reference ranges varies from 40nmol/l to 65nmol/l Some of this variation is due to the differences in the assays used, but any otherwise healthy cat with a tT4 of more than 40nmol/l should be regarded as borderline hyperthyroid; many laboratories now report this as a “grey” zone.
In many cats with a tT4 more than 40nmol/l, a second sample four to 12 weeks later will reveal an elevated diagnostic tT4. If the second sample is still borderline, and the cat has clinical signs (such as goitre or weight loss), it should be carefully evaluated for concurrent illness.
The serum free thyroxine (fT4) concentration should additionally be measured. A tT4 of more than 40nmol/l and an elevated fT4 (more than 40pmol/l, depending on the laboratory) can be considered diagnostic for hyperthyroidism in an otherwise healthy cat.
Hyperthyroidism can be very difficult to diagnose in cats with concurrent illness 10. In my experience, around 50 per cent of cats with mild to moderate CKD and hyperthyroidism will have a tT4 within the reference range when it is first suspected clinically. Hyperthyroidism usually causes a drop in creatinine concentrations, which practitioners should pick up if they are monitoring CKD cases regularly10.
A proportion of these cats with concurrent disease may never develop a high tT4, or the tT4 will take months or years to rise above the reference range. However, they may experience severe symptoms of hyperthyroidism.
In a cat with concurrent illness and clinical signs compatible with hyperthyroidism, a tT4 of more than 30nmol/l can be considered suspicious of hyperthyroidism10. On rare occasions, hyperthyroidism may even be diagnosed in very sick cats with a tT4 concentration less than 30nmol/l.
Free T4 may be elevated in around 10 to 20 per cent of euthyroid cats with concurrent illness (false-positive result)10, 22, 23 and, therefore, fT4 should not be used alone for the diagnosis of hyperthyroidism, especially in a sick cat. However, the concurrent measurement of fT4 (more than 40pmol/l) and tT4 (more than 30nmol/l) may be useful as a diagnostic test in cats with concurrent illness and clinical signs suggestive of hyperthyroidism10, 24.
If measurement of tT4 and fT4 is not helpful, or the results are equivocal but you still suspect hyperthyroidism, a T3 suppression test is an alternative choice for a further work-up.
Unfortunately, about 20 to 30 per cent of apparently healthy senior cats have a low TSH concentration (less than 0.03ng/ml; see the section entitled subclinical hyperthyroidism), which is the same as cats with hyperthyroidism and, therefore, TSH measurement cannot be used alone as a diagnostic test.
However, a TSH of more than 0.03ng/ml can be used to rule out a diagnosis of hyperthyroidism, and this may be of particular use in sick cats with high normal tT4 and/or borderline high fT410.
It is important to consider the possibility that a cat with high normal creatinine (more than 140μmol/l) and high normal tT4 concentration (more than 30nmol/l) has concurrent kidney and thyroid disease.
Some cats will have obvious CKD prior to, or at the time of, hyperthyroidism diagnosis. However, low muscle mass, combined with the increased glomerular filtration rate (GFR) in hyperthyroid cats, can mask CKD. The majority of hyperthyroid cats with CKD will not be azotaemic at diagnosis. All cats should have their renal function evaluated four to eight weeks after the initiation of treatment for hyperthyroidism, as 20 to 50 per cent of cats will show evidence of renal dysfunction following treatment of their thyroid disease.
A small study indicated cats that develop mild stable CKD after treatment for hyperthyroidism do not have a worse prognosis than cats without evidence of CKD following treatment ()26.
Therefore, the emergence of CKD following treatment of hyperthyroidism is not an indication for stopping treatment, as advocated in some texts. However, in cats with concurrent moderate to severe kidney disease and hyperthyroidism, the effects of hyperthyroidism in increasing the GFR can have a palliative effect on kidney function. In addition, the hyperthyroidism may have a beneficial effect in maintaining the cat’ s appetite. The hyperthyroidism in these cats should be treated cautiously and, indeed, such cats have a poor prognosis.
The onset of hyperthyroidism may be due to an increased vascular resistance following the treatment of hyperthyroidism. Ideally, systolic blood pressure should be monitored before and after the treatment of hyperthyroidism using the Doppler method.
The three main treatment modalities for hyperthyroidism are radioactive iodine, surgical thyroidectomy and medical treatment with methimazole or carbimazole. Radioactive iodine is an extremely safe and effective way to treat hyperthyroidism in cats. However, it remains an expensive and specialist treatment that requires hospitalisation for up to four weeks at a referral facility. Many first opinion practices favour a unilateral thyroidectomy over a bilateral thyroidectomy if there is a unilateral goitre. This significantly decreases the potential for post-surgical hypocalcaemia following iatrogenic damage to the parathyroids.
However, it should be recognised that around 60 to 70 per cent of cats have bilateral disease and, therefore, a unilateral surgery will often be followed by the recurrence of thyroid disease.
Studies have shown a low incidence of hypocalcaemia following bilateral thyroidectomy when surgery was performed by a specialist surgeon, and recurrence occurred in less than 10 per cent of cats.
Most cats are treated with antithyroid medication and/or betablockers (such as atenolol) prior to surgery, as this reduces the risk of anaesthetic problems. It is also important to review a complete blood count prior to surgery in cats on oral anti-thyroid medication, as both carbimazole and methimazole can be associated with thrombocytopaenia.
Many cats that tolerate medication are treated long term with oral anti-thyroid medication. Although this may be perceived to be a “cheaper” option, these cats need regular monitoring with blood tests to check tT4, kidney function and blood cell counts, and the medication can be expensive. With an average life expectancy in treated hyperthyroid cats of two to three years following treatment27, 28, the long-term cost of maintaining euthyroidism by medication alone is unlikely to be different than surgery or even radioactive iodine.
Total thyroxine should be measured three to four weeks after starting treatment and then every three to six months, presuming the cat is stable.
This could occur more frequently if necessary. Hyperthyroidism is not adequately controlled unless the tT4 is less than 40nmol/l; the ideal range is about 10nmol/l to 30nmol/l.
Although cats are not thought to suffer significantly from hypothyroidism, it is recommended to decrease the dose of oral medication if the tT4 drops below 10nmol/l – especially in cats with concurrent renal dysfunction.
In cases of cats that initially appear to be well controlled with neomercazole, and where the owners do not appear to have any problems medicating their pets, intermittently high tT4 concentrations can still be present.
Owner and cat compliance is a major problem with longterm medical treatment and, therefore, radioactive iodine or surgery should be recommended after stabilisation with medication, especially for otherwise healthy cats less than 15 years of age.
Figure 1. Histopathology of feline hyperthyroidism: a small hyperplastic nodule surrounded by a normal thyroid tissue.
Figure 2. Kaplan Meier survival curve of three groups of hyperthyroid cats, divided according to their creatinine concentrations prior to and after treatment for hyperthyroidism. This shows that cats with less than 177μmol/l prior to treatment for hyperthyroidism did not have a significantly different survival rate, irrespective of post-treatment creatinine concentrations. However, cats with azotaemia prior to treatment of hyperthyroidism (creatinine less than 177μmol/l) had a significantly lower survival than the other two groups (p<0.001). Survival is compared at the 0.5 cumulative mark on the Y axis29.
Figure 3. An example of a hyperthyroid cat.
Jennifer Wakeling
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