David B. Church, BVSc, PhD, MACVSc, MRCVs, ILTM
Department of Veterinary Clinical Sciences, The Royal Veterinary College North Mymms, Hatfield, Hertfordshire, UK
In contrast to the dog, where hypothyroidism is the most common thyroid disorder, hyperthyroidism or thyrotoxicosis is the most common thyroid problem in the cat.
Since the first clinical reports of feline thyrotoxicosis in 1979 the condition has been recognized with increasing frequency. The explanation for this increasing prevalence remains unclear but seems unlikely to be solely due to increased recognition or longer average life span. Whatever the reasons they seem to be only influencing the feline and not the canine population as thyrotoxicosis remains an extremely uncommon disorder in dogs. Feline thyrotoxicosis results from the spontaneous development of hyper functional thyroid nodules and is not usually associated with malignant thyroid neoplasia. A similar problem occurs in people under the name "toxic nodular goiter".
Although there are some similarities between the disease in man and cats there are also some significant differences. Thyrotoxic cat thyroid glands contain single or multiple, autonomously functioning and growing nodules. It seems neither growth nor hyperfunction of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells. The factors enhancing transformation of normal thyroid to a nodular hyperfunctioning goiter over many years are still unknown. Immunological, environmental and nutritional factors are the focus of on-going studies, but an infectious agent cannot yet be excluded.
This is basically a disease of middle to old age. In one recent study 90% of affected cats were 11 years or older. The most common presenting complaint is significant weight loss. This is often accompanied by polydipsia as well as increased or decreased appetite and occasionally vomiting. Increased faecal volume and even diarrhoea may be associated with some cases. Affected animals may be hyperactive and occasionally aggressive or alternatively they can be lethargic and generally under-responsive.
Although signs of congestive heart failure are uncommon in thyrotoxicosis many affected cats have mild to moderate hypertrophic cardiomyopathy that usually results in an increased cardiac impulse with or without a systolic murmur most audible over the heart base.
A discrete thyroid mass can be palpated in up to 90% of affected cases however it should be remembered that many older cats can have palpable thyroid nodules which are clinically insignificant while not all thyrotoxic cats have a palpable lesion.
Routine Clinical Pathology
There are non-specific changes found on the haemogram that may include erythrocytosis and a stress leukogram. Mild to marked elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) are the most common biochemical abnormalities in feline hyperthyroidism. Analyses of various clinical case series suggest approximately 90% of hyperthyroid cats have an elevation in one of these three enzymes. However this does not mean that an absence of an elevation in one these three enzymes precludes a diagnosis of hyperthyroidism and indeed as our index of suspicion for the disease is increased and the animals are detected earlier in the course of the disease it is conceivable that future analyses may shoe this proportion has declined.
Additionally mild to moderate increases in urea and creatinine may be found in over 25% of hyperthyroid cats, while hyperphosphataemia without azotaemia can be found in up to 20% of hyperthyroid cats.
Basal Total T4
Elevated basal plasma T4 concentrations are pathognomonic for thyrotoxicosis in a mature cat although a normal plasma T4 does not preclude the diagnosis as plasma total T4 and free T4 can fluctuate within the normal range in thyrotoxic cats over a period of days.
Furthermore any stressful complications will tend to lower basal T4, resulting in an overtly thyrotoxic cat having a basal T4 level within the normal range.
Consequently, for a number of reasons an animal may have all the clinical features of thyrotoxicosis but not have an elevated basal T4. In these cases where there is a strong clinical impression of thyrotoxicosis and a non-confirmatory basal TT4 a number of alternatives can be considered.
Firstly it may be prudent to simply wait for a month or so and repeat the basal TT4 test after advising the owner that if the cat is thyrotoxic there is a possibility of acute deterioration at any time.
Basal Free T4
Performing a free T4 by equilibrium dialysis (edFT4) may be clarifying in some cases as it has been reported that some thyrotoxic cats with normal total T4's will have an elevated edFT4. Unfortunately, some non-thyrotoxic cats can have elevated edFT4, making it unwise to use the edFT4 assay as the screening test for thyrotoxicosis.
A number of reports have also shown that scintigraphy may be helpful in determining thyrotoxic patients as almost all will have asymmetric, excessive technicium uptake. Unfortunately accurate scintigraphic scanning is very operator and equipment dependent. Any evaluation of feline thyroid scintigraphy will require specialist interpretation, making this an alternative available to only a few.
A satisfactory alternative may be dynamic testing of thyroid function. The most reliable dynamic method of absolutely ruling out thyrotoxicosis is to perform a T3 suppression test.
The T3 suppression test utilises the TSH suppressive effect of elevated levels of plasma T3. Decreased TSH production will result in a significant reduction in endogenous T3 and T4 synthesis and secretion in normal thyroid tissue. As feline thyrotoxicosis is caused by autonomously functioning thyroid tissue, administration of T3 to thyrotoxic animals does not produce a significant decline in plasma T4 levels.
The test is performed sampling plasma total T4 levels before and after a set period of orally administered T3. The 25 ug of T3 is administered every 8 hours for two days. One the morning of the third day T3 is administered (a total of 7 doses and a total dose of 175 ug) and the cat returned within 8 hours for repeat total T4 sampling.
Although a number of different methods of interpreting T3 suppression tests have been reported the simplest and most sensitive remains comparing before and after absolute total T4 levels. After T3 administration plasma total T4 values are less than 20 nmol/l in cats who do not have thyrotoxicosis while thyrotoxic cats have post T3 plasma total T4 concentrations greater than 20 nmol/l.
Currently T3 is only available as Tertroxin in 20mg tablets. As the major limitation for this test is the unknown of whether the cat actually received the tablets, it should be stressed to owners that their cat must receive one and one quarter tablets three times daily. Although there is a temptation to put the tablets in the food it is perhaps a little too unreliable in this setting.
It should be remembered there have been a number of anecdotal reports of an acute deterioration in renal function after treatment for thyrotoxicosis. This has been an unusual occurrence and generally has been confined to cats with clear evidence for azotaemic renal failure prior to treatment. Perception of this possibility is sufficiently dramatic to justify warning owners that there is a possibility that treatment may precipitate an acute deterioration in renal function in individual cats. It is for this reason that some clinicians justify a preliminary trial with a readily reversible antithyroid management strategy such as methimazole before committing the cat to a less reversible anti-thyrotoxic treatment strategy such as surgery or irradiation. It is also worth noting that while there is not an increased prevalence of hypertension in untreated hyperthyroid cats, recent reports have suggested that sometime within the first 6-12 months after correction of hyperthyroidism individuals may become hypertensive. Consequently it would seem prudent that whenever possible, not only total T4 but also blood pressure is measured as part of these patients' regular re-evaluation visits.
Radioactive Iodine I 131
Radioactive iodine administration provides a remarkably simple, effective and safe method of treating feline thyrotoxicosis. The dose of I131 required varies with route of administration. Generally lower doses are required if the I131 is administered parenterally rather than orally although oral preparations are less expensive. The main disadvantages to radioiodine treatment are the inconvenience in obtaining authorisation and facilities to permit handling and disposal of the isotopes. At present only a small number of facilities are registered to perform this treatment in the UK although all take referrals.
Because of the practical limitations with radiotherapy and the potential compliance problems with medical management, surgery continues to be offered as an alternative treatment for thyrotoxicosis. It should be remembered that these animals have underlying cardiac disease which increases the risk associated with general anesthesia.
Because a reasonable proportion of cases present with a unilateral nodule, unilateral thyroidectomy can be performed and in a significant number of cases will result in resolution of clinical signs for variable periods of up to 12-15 months when almost always hyperthyroid signs will return usually with a contralateral nodule which will require removal and possibly long-term thyroid supplementation.
This sequence of events can be avoided by performing bilateral thyroidectomy using an extracapsular procedure however the surgery needs to be meticulous and although much less common with this modified technique, complications (particularly acute hypoparathyroidism) can be life threatening. Consequently, preferably an experienced surgeon should perform surgical correction of thyrotoxicosis using this modified extracapsular technique.
A third alternative is the use of antithyroid drugs of the thiourylene class, which lower elevated circulating thyroid hormone levels through blockage of thyroid hormone synthesis. Carbimazole has been available in Europe for sometime while methimazole was the principal thiourylene used in North America. Recently methimazole has been specifically licensed for use in hyperthyroid cats in the United Kingdom and as such should be the first choice for medical management. Methimazole is initially recommended at an oral dose of 10-15mg per day given in two to three divided doses. The initial dose is usually recommended for two to three weeks, generally resulting in control of signs of hyperthyroidism in approximately 90% of affected cats. While an impression of progress or otherwise can be obtained by clinical evaluation, more objective criteria may include reductions in the elevations of ALT and particularly ALP as well as of course total T4.
With the increasing trend of earlier recognition and hence management of less severely affected cases, there is a greater tendency to use lower initial doses of methimazole (2.5 or 5mg twice daily). This is further supported since in the UK methimazole is currently licensed for pre-operative or rapid stabilisation at 5mg q12h for 3 weeks. If euthyroidism is not achieved in this period the duration of treatment is increased or the dose increased in 2.5 or 5 mg increments.
Once euthyroidism has been achieved with this remission inducing dose of methimazole, the daily dose is adjusted down with 2.5-5mg decrements aiming for the lowest possible dose that maintains the euthyroid state. Further dose adjustments are based on total T4 estimations that occur as frequently as required to obtain stability, then usually 3 to 6 monthly. In earlier studies most cats required 15-20 mg per day to maintain euthyroidism however with the milder degree of clinical signs seen in cases diagnosed in the 21st century many cats can be maintained on doses as low as 2.5-5mg per day. However as only 5 mg tablets are currently available, limiting the potential for lower doses. However although methimazole's half-life in relatively short (4-6h) its intrathyroidal residence time is closer to 20 hours. Consequently although divided doses may be more effective in rapid euthyroid induction, at 4 weeks time there is no difference in chronic efficacy between 2.5 mg q12hourly and 5 mg q24 hourly.
Both may produce adverse reactions in up to 15% of cases and have the disadvantage of requiring at least once daily dosing for adequate suppression of plasma thyroid hormone levels. While this is clearly more attractive than twice daily tableting owner compliance can be an issue and, on balance, in the author's opinion, radioactive iodine is definitely an attractive treatment option for feline thyrotoxicosis. The effect of prior methimazole treatment on the eventual outcome of radioactive iodine treatment is controversial although a recent study has suggested that it has virtually no effect or if anything may lower the dose of I131 required to achieve euthyroidism.