Feline Hyperthyroidism
World Small Animal Veterinary Association World Congress Proceedings, 2004
Boyd R. Jones, BVSc, FACVSc, DECVIM, MRCVS
Faculty of Veterinary Medicine, University College Dublin
Belfield, Dublin, Ireland

Hyperthyroidism has become the most common endocrinopathy of middle aged and older cats, worldwide. Younger cats (<5%) can be affected but there is no breed or sex predilection. The clinical signs of hyperthyroidism result from excessive circulating concentration of thyroxine (T4), triiodothyronine (T3) which are produced by a functional thyroid tumour or hyperplastic adenomatous thyroid tissue one or both lobes. Thyroid carcinoma is rare. The pathogenesis of hyperthyroidism and the means by which the thyroid tissue becomes hyperplastic or neoplastic is not fully understood.

Clinical Signs

The clinical signs of hyperthyroidism are summarised in table 1. The signs are associated with the effect of excess thyroid hormones on metabolic functions of a variety of organs and tissues. The most consistent signs are increased activity and appetite with weight loss, muscle wasting, heat intolerance and tachycardia. Not all signs are present in any one cat and in the early stages of the disease few signs may be present and only subtle differences from normal are apparent.

Diagnosis

Hematological changes include moderate erythrocytosis and macrocytosis. The most regular biochemical abnormalities observed are elevations in liver enzymes; alanine aminotransferase (ALT) and serum alkaline phosphatase (ALP). At least one of these enzymes is elevated in over 90% of hyperthyroid cats. Other changes include hyperphosphatasemia in the absences of azotemia. Serum calcium values are usually within the reference range. Hypokalemia is reported in some hyperthyroid cats. Serum biochemistry measurements also help to rule in or out other concurrent conditions such as renal disease and diabetes mellitus. Hyperthyroidism can mask renal insufficiency and overt renal disease can be precipitated by treatment of hyperthyroidism.

Hyperthyroidism can be confirmed by the demonstration of increased thyroidal radioisotope uptake (131I or 99mTcO4). In addition scintigraphy is a useful procedure to determine unilateral or bilateral thyroid gland involvement or the site of accessory, ectopic or metastatic thyroid tissue.

Table 1. Clinical signs and findings on clinical examination in cats with hyperthyroidism

Clinical Signs

Findings on Examination

Polyphagia

Thin/Cachectic

Weight loss

Difficult to examine

Hyperactive

Palpable thyroid

Anxious/nervous

Heart murmur

Polydipsia/Polyuria

Tachycardia

Unkempt hair coat

Arrhythmia

Alopecia and unkempt coat

Alopecia and unkempt coat

Vomiting

Long nails

Diarrhoea/Bulky stools

Aggressive

Panting/Dyspnoea

Depressed*

Lethargy/Depression*

Weakness*

Anorexia*

Ventroflexion neck*

* Uncommon signs

The characteristic clinical signs and findings on clinical examination (especially a palpable thyroid tumour) and elevated concentrations of thyroxine (T4) or tri-iodothyronine (T3) support a diagnosis of hyperthyroidism. However, some cats with hyperthyroidism (2-10%) have serum concentrations of both T4 and T3 that are within the reference range. If hyperthyroidism is suspected, but the serum T4 or T3 concentration is not high, repeat the basal T4 measurement 1-2 weeks later. Ensure non-thyroidal illnesses which can suppress the circulating thyroid hormone concentrations are eliminated. If the result is again in the mid-to high-normal reference range and hyperthyroidism is still suspected, determination of a free (unbound) T4 concentration (by a dialysis method) is recommended. Because only the free fraction of thyroid hormone is available for entry into the cells, free T4 provides a more sensitive assessment of thyroid status. Free T4 is less likely to be influenced by non-thyroidal illnesses. If free T4 by a dialysis cannot be measured, provocative testing by use of a T3 suppression test or thyrotropin-releasing hormone (TRH) stimulation test should be performed.

Treatment

There are three methods of treating hyperthyroidism; medical management, surgical thyroidectomy or radioactive iodine (131I). The treatment selected is individual to each cat and the choice depends on a number of important factors; the age of the cat, the presence of cardiovascular abnormalities and/or concurrent diseases (e.g., diabetes mellitus, renal disease), cost, availability of nuclear medicine facilities, surgical skills of the veterinarian and the owners acceptance of a particular treatment and their compliance.

Medical treatment is aimed at reducing the effects of increased thyroid hormone secretion; the administration of B blockers to reduce blood pressure and calcium channel blockers to slow the heart rate or anti-thyroid drugs (e.g., methimazole and carbimazole) which reduce the T4 and T3 concentration but since they do not destroy adenomatous tissue a relapse will occur within 24-72 hours if medication is stopped. The dose of drugs used for the medical treatment of hyperthyroidism are shown in table 2. Recently topical treatment with methimazole has been applied to treat hyperthyroid cats. Side effects that occur with oral methimazole medication are listed in table 3 and are mostly seen in the first weeks of treatment. Most are mild and transient and discontinuation of medication is not required. Monitoring of serum biochemistry and haematology in the first 3 months is recommended.

Surgical thyroidectomy is an effective treatment and is most often successful but it can be associated with significant morbidity and mortality. Thyroidectomy is a relatively simple procedure but cardiovascular, hepatic and gastrointestinal dysfunction associated with hyperthyroidism greatly increase anaesthetic and surgical risks. There are a number of factors that must be considered to ensure a successful outcome. About 30% of hyperthyroid cats have disease in only one thyroid lobe whereas the remaining 70% have bilateral thyroid lobe involvement. In cats with unilateral thyroid tumours, the contralateral lobe is normal in position and either normal or small in size when seen at surgery. Hemithyroidectomy corrects the hyperthyroidism but relapse, resulting from the development of adenomatous changes in the remaining 'normal' thyroid lobe occurs but sometimes takes years to develop. In cats with bilateral thyroid adenomas (adenomatous hyperplasia), removal of both lobes with preservation of parathyroid glands is necessary to control hyperthyroidism and avoid postoperative hypocalcaemia. With bilateral thyroid tumours, enlargement of both lobes can be identified at surgery in most cats, however, about 15% of cats with bilateral lobe involvement have one lobe which is only slightly enlarged and it may not be possible to determine if it is abnormal. Preoperative thyroid imaging can determine the extent of thyroid lobe involvement but if thyroid imaging is not possible, removal of the obviously enlarged lobe with preservation of its external parathyroid gland. Preservation of the external parathyroid gland during hemithyroidectomy minimises the risk of hypoparathyroidism should removal of the contralateral lobe be required at a later date when hyperthyroidism returns.

Table 2. Drugs used in the management of hyperthyroidism (after Mooney 1998)

Drug

Mode of action

Formulations

Indications

Dosage

Contraindications

Carbimazole/
Methimazole

Inhibition of thyroid peroxidase-catalysed reactions

5mg tablets

Before surgery
Chronic management

5mg q 8hr
5mg q 12hr

The occurrence of side effects
Non-compliance by owner
Unsuitable patient

Propranolol

β12-adrenoceptor blocking agent

10mg tablets

Before surgery
Symptomatic control

2.5-5mg q 8hr

Alone, before surgery
Chronic management

Atenolol

β1-adrenoceptor blocking agent

25mg tablets
25mg/5ml syrup

Before surgery
Symptomatic control

6.25-12.5mg q
24 hr

Alone, before surgery
Chronic management

Calcium ipodate

Inhibits peri-pheral T4 to T3 conversion
Releases iodine

500mg capsules

Before surgery

15mg/kg q
12 hr

Before 131I therapy

Chronic management

Diltiazem

Calcium channel blocker

10 mg tablets

Alternative to beta blocker if they are contraindicated

7.5 mg per os q 12 hr

Chronic management

Reduced cardiac output

Table 3. Abnormalities associated with methimazole therapy in 262 cats with hyperthyroidism

Time to develop
(days)

Clinical signs and pathology

Percentage
of cats

Mean

Range

Clinical Signs

Anorexia

11

24

1-78

Vomiting

11

22

7-60

Lethargy

9

24

1-60

Excoriations

2

21

6-40

Bleeding

2

31

15-50

Clinical Pathology

Positive antinuclear antibody titre

22

91

10-870

Eosinophilia

11

57

12-490

Lymphocytosis

7

25

14-90

Leukopenia

5

23

10-41

Thrombocytopenia

3

37

14-90

Agranulocytosis

2

62

26-95

Hepatopathy

2

39

15-60

(adapted from Peterson ME et al 1988 )

The complications associated with thyroidectomy include hypoparathyroidism, Horner's syndrome and laryngeal paralysis. The most serious complication is hypocalcaemia, which develops after the parathyroid glands are injured, devascularised or inadvertently removed in bilateral thyroidectomy. After bilateral thyroidectomy, the serum calcium concentration should be measured daily until it has stabilised within the reference range. In most cats with iatrogenic hypoparathyroidism, clinical signs associated with hypocalcaemia will develop within 1-3 days of surgery. Although mild hypocalcaemia (1.6-1.9 mmol/l) is a common finding during this immediate postoperative period. If signs of muscle tremors, tetany or convulsions develop, treatment with calcium and later vitamin D are indicated. A low blood concentration of calcium without clinical signs does not require treatment. Cats that have a thyroidectomy should have a serum thyroid hormone concentration measured once or twice a year.

Radioactive iodine (radioiodine 131I) provides a simple, effective and safe treatment for cats with hyperthyroidism. Radioiodine, like stable iodine, is concentrated by the thyroid gland after administration, primarily in the hyperplastic or neoplastic thyroid cells where it irradiates and destroys the hyperfunctioning tissue. Normal thyroid tissue, however, tends to be protected from the effect of radioiodine, since the uninvolved thyroid tissue is suppressed and receives only a small dose of radiation.

Radioiodine is the best treatment when nuclear medicine facilities are available. Radioactive iodine treatment involves a single, simple procedure that is without associated morbidity or mortality. Untoward systemic effects have not been observed. Unlike surgery, anaesthesia is not required. A single 131I treatment will restore euthyroidism in most cats with hyperthyroidism and cats that remain persistently hyperthyroid can be successfully retreated with radioiodine and those that become hypothyroid can be supplemented readily with thyroxine. Special radioiodine materials licensing and facilities are required for the treatment of hyperthyroid cats in most countries.

References

1.  Peterson, ME; Kintzer, PP; Cavanagh, PG; et al. Feline hyperthyroidism: pre-treatment clinical and laboratory evaluation of 131 cases. J Am Vet Med Assoc, 1983; 183: 103-110.

2.  Mooney, CT. Feline hyperthyroidism. Diagnostics and therapeutics. Vet Clin North Am Sm Anim Pract, 2001; 31: 963-983.

3.  Peterson, ME; Melian, C; Nichols, R. Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. J Am Vet Med Assoc, 2001; 218: 529-536.

4.  Peterson, ME; Kintzer, PP; Hurvitz, AL. Methimazole treatment of 262 cats with hyperthyroidism. J Vet Intern Med, 1988; 2: 150-157.

Speaker Information
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Boyd R. Jones, BVSc, FACVSc, DECVIM, MRCVS
Faculty of Veterinary Medicine, University College Dublin
Belfield, Dublin, Ireland


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