General Considerations

Hyperthyroidism is the most common endocrinopathy of domestic cats. It is usually the result of thyroid adenoma(s) or multiple hyperplasic nodules which may be unilateral or bilateral. Not all nodules are palpable. Functional thyroid tissue may elaborate increased amounts of thyroxine (T4) and T3, producing clinical signs including a loud and fast heart, a prominent precordial impulse, a strong pulse, weight loss with good appetite, heat intolerance, behavioural changes and polydipsia/polyuria. Untreated, hyperthyroidism damages a variety of end organs, particularly the heart and kidneys. The resulting catabolic state likely foreshortens life expectancy.

Hyperparathyroidism is reported to be rare in geriatric cats, but is likely under-diagnosed. A functional parathyroid tumour secretes parathyroid hormone (PTH), causing hypercalcaemia, which causes azotaemia, polyuria, incessant polydipsia, sporadic vomiting, twitching and reduced appetite. These signs also occur with chronic renal insufficiency which can confuse the issue, as many elderly cats have at least some degree of kidney dysfunction. Furthermore, some cats have concurrent thyroid and parathyroid lesions.

Experienced veterinarians can palpate ventral cervical nodules(s) in many old cats--some are thyroid in origin, others are parathyroid. Some are functional, some are non-functional or "pre-functional". Indeed, the presence of an incidental mass in the cervical/(para)thyroid area is an enigma in feline medicine because the only reliable way to distinguish thyroid from parathyroid masses is surgical biopsy. This may not be justified if lesions are non-functional, which is often the case early in the clinical course when spot T4 and calcium determinations are in the reference interval.

The presence of a palpable thyroid nodule is one of the cornerstones in securing a diagnosis of hyperthyroidism, but a functional hyperthyroid state must be confirmed on the basis of other characteristic physical findings, specifically tachycardia, an enlarged cardiac impulse, a systolic heart murmur or gallop rhythm, and documented weight loss (in the face of a good appetite). A firm presumptive diagnosis is often made on the basis of these findings.

Diagnosis

It is usually straightforward to confirm the diagnosis using simple laboratory studies, such as a serum biochemistry panel and T4 determinations. It is prudent to do a urinalysis as well to assess urine concentrating ability. Many cats with hyperthyroidism have increased activities of alkaline phosphatase and alanine aminotransferase. Diabetes mellitus should be ruled out in cats with weight loss in the face of good appetite. If calcium concentration in the biochemical panel is high, or even high normal, consider an ionised calcium determination and measuring the serum PTH concentration. Both of these tests are a bit tricky, but with an I-Stat unit or blood gas analyser you can achieve the former, while to achieve the latter you need to freeze the serum specimen quickly and make sure it remains on ice on the way to a reputable endocrine laboratory. Diagnosis of hyperparathyroidism is rarer but these cases can be very gratifying to treat.

Often a single T4 determination is sufficient to diagnose hyperthyroidism. Sometimes a 2nd T4 determination will be required, and in a small number of troublesome cases one has to resort to free T4 determination using equilibrium dialysis or (better) a T3 suppression test. Scintigraphy can also be useful. If the cervical mass is large, ultrasound the lesion with the highest frequency transducer you have. Large lesions are often cystic. If they have an anechoic centre it is worth aspirating the fluid. Thyroid masses tend to contain bloody fluid, whereas parathyroid masses tend to contain clear fluid. You can also determine T4 and PTH levels in the fluid, if you get enough, and this can be helpful in determining the nature of the nodule.

Be wary of diagnosing hyperthyroidism on the basis of a T4 determination in the absence of supportive clinical findings. Laboratory procedures are rarely perfect, and a falsely elevated T4 concentration is not unheard of in a euthyroid cat. Fortunately, most sick cats tend to have low T4 levels (euthyroid sick syndrome).

An important part in the evaluation of geriatric cats is the detection of co-morbidities, especially chronic renal insufficiency. This is critical because cats with a marginal glomerular filtration due to renal disease are reliant on the augmented cardiac output of the thyrotoxic state to maintain their urea and creatinine concentrations within normal limits.

Treatment

Radio-iodine is the treatment of choice for cats with hyperthyroidism.

The following specific considerations apply to I-131 therapy:

1.  It is reliable and highly effective when a dose of between 160 and 250 MBq is given (depending on the size and no. of thyroid nodules, and the extent of the T4 elevation; most cats need 150 to 200 MBq). In Australia we seem to err on the side of giving too much, rather than not enough.

2.  From the point of view of the cat, I-131 is safe and not stressful to administer as either a capsule or a subcutaneous injection. We prefer the capsules (less expensive), but the injections are superior for feisty cats that may be hard to pill. Our regulatory authorities require cats to be hospitalised for about 5-7 days.

3.  There is no requirement for anaesthesia or surgery, and no risk of post-operative hypocalcaemia, laryngeal paralysis, etc.

4.  It fixes the problem, generally permanently, at the first attempt and without side effects.

5.  In most facilities, in Australia at least, I-131 therapy will "cost out" cheaper than bilateral staged thyroid surgery.

6.  A variety of therapy centres exist in different areas. The development of commercially available purpose-built cages makes radio-iodine therapy possible in any practice with a start-up cost of less than $10,000 AUD, including training and licensing. There is insufficient evidence in the peer reviewed literature to recommend the additional cost of routine thyroid scans prior to I-131 therapy. Simple tables that take into consideration the size of the thyroid lesion(s) and the extent of the T4 elevation seem adequate to determine the radioiodine dose.

7.  From a pathophysiological point-of-view, radio-iodine fixes the underlying problem, i.e., the abnormal thyroid tissue is ablated. Other non-specific effects of the thyroid lesion, e.g., paraneoplastic substances, mass effects are avoided.

8.  There is no requirement for twice daily medication and regular trips to the veterinary clinic to maintain a euthyroid state. In contrast, cats treated with carbimazole or methimazole typically require frequent and careful monitoring. The dose of medication may change as the primary lesion gets larger.

9.  The presence of concurrent parathyroid lesions becomes apparent, as abnormal thyroid tissue is ablated by the I-131. Thus, the detection of concurrent parathyroid lesions--either functional or non-functional--is facilitated.

10.  Under dosing with radio-iodine requires that the cat be given a 2nd dose at some point in time, typically after waiting 6 months for delayed effects of treatment.

11.  Over dosage with radio-iodine can result in permanent hypothyroidism, although this is rare. Transient hypothyroidism occurs in most patients, and is the stimulus for increased TSH levels to "kick start" normal thyroid tissue that was previously quiescent. Signs of permanent hypothyroidism include lethargy, a poor coat and myxoedema of the head, resulting in thickened facial features and mild stridor referable to the upper airways. Hypothyroidism is easily treated with replacement therapy, typically 100 µg of thyroxine once daily. This requirement is constant. It is noteworthy that many human patients with Graves' disease are treated with ablative radio-iodine, and subsequently given life-long replacement therapy. Because thyroxine is a natural substance, it is well tolerated.

12.  Much is made of the risk of "unmasking" renal insufficiency following treatment of hyperthyroidism. However, if cats have urea and creatinine concentrations within the reference range, and a urine sg > 1.025 (>1.035 is even better!), it is rare for them to develop clinically significant azotaemia following therapy with I-131. It should be emphasised that urea and creatinine concentrations in cats with hyperthyroidism generally do rise to some extent following re-establishment of euthyroidism. Unfortunately some cats develop the uraemic syndrome following therapy (particularly very old cats).The only definitive way to determine whether this will occur is with a carbimazole trial, which adds greatly to the cost and complexity of therapy. Renal insufficiency following I-131 therapy can still be managed using prescription diets, phosphate binders, and attention to hydration; it is prudent to also treat them with supra-physiological doses of thyroxine to re-establish a slightly hyperthyroid state and thereby increase renal blood flow.

13.  It may be prudent not to treat cats with clinical or biochemical evidence of renal insufficiency--even though some of these cats will actually benefit from correction of their thyrotoxicosis. A good way forward in this situation is a trial with carbimazole--although sometimes adverse effects from this drug trial can be problematic. Another strategy is to manage the cardiac signs of thyrotoxicosis with atenolol, treat hypertension with amlodipine and forgo any attempt to treat the underlying problem specifically.

14.  The current cost of therapy ($900-1200 AUD) is acceptable and less expensive in the long term than on-going medical management for 6-12 months.

Thyroidectomy

Surgical management of hyperthyroidism--either using a staged bilateral approach, or one nodule at a time--has most of the advantages of radio-iodine. Risks associated with anaesthesia are less than in the 1980/90s because of earlier diagnosis and the widespread use of modern induction regimens, isoflurane or sevoflurane for maintenance, intra-operative fluid support and good intra and post-operative analgesia. For these reasons, risks are extremely small (as has recently been shown in a European study), especially if cats are rendered euthyroid with carbimazole therapy prior to surgery.

Surgery is especially attractive in the following circumstances:

1.  When the owner will not travel to a referral centre.

2.  When there is an easily accessible large unilateral nodule.

3.  When a thyroid mass is present and growing--without clear cut signs of either hyperthyroidism or hyperparathyroidism. Indeed, it could well be that early surgical intervention is more appropriate than we currently realise, removing thyroid and parathyroid lesions before the adverse effects of endocrine hyperfunction develop, and while the mass is small.

4.  When the clinician is prepared to accept less than "the going rate" for surgery because of a desire to help the patient and/or the client. In experienced hands, this is an easy and quick surgery that generally goes well as long as only removal of unilateral lesions is attempted.

There is the additional benefit that histopathology provides a definitive diagnosis. There are, however, dangers of inexperienced surgeons attempting bilateral thyroidectomy, and the risk of post-operative hypocalcaemia is sufficiently high that this technique cannot (in my opinion) be recommended as a single procedure. Norsworthy's idea of doing one side at a time, with transplantation of normal parathyroid to the strap muscles is clever, safe and easy. An instructional video of this technique is available.

Long Term Carbimazole Therapy

My negative view of carbimazole comes from having been referred many cases where it has either failed to produce the expected euthyroid state, or produced unacceptable side effects. The latter are not trivial in a geriatric cat with several concurrent problems, and I have seen many cats euthanased because of the development of carbimazole-induced problems, which have resulted in the owners losing a positive attitude towards ongoing case management. Clients can lose confidence in the veterinary team if it takes some time for the cat to become outwardly normal, and if the cat requires what the owner perceives as an excessive number of veterinary consultations. For owners who want the problem fixed quickly at the first attempt, radioiodine or surgery is more appropriate than carbimazole.

From my perspective, the principal issues with this drug are:

1.  The underlying problem is never fixed.

2.  Concurrent hyperparathyroidism may be missed until the serum calcium concentration has been elevated for quite some time.

3.  The requirement for the drug is variable and many cats need frequent dose alterations.

4.  There are compliance issues for many owners.

5.  There are ongoing bills and the need for regular veterinary consultations.

6.  Specific drug-related adverse effects that have been recorded include gastrointestinal side effects (anorexia, vomiting, diarrhoea), symptomatic thrombocytopenia, neutropenia and liver dysfunction.