APPROACHES TO HYPERTHYROIDISM

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1 Vet Times The website for the veterinary profession APPROACHES TO HYPERTHYROIDISM Author : Catherine F Le Bars Categories : Vets Date : June 29, 2009 Catherine F Le Bars explores instigating factors for this often-seen disease and outlines effective treatment modalities and future diagnostic developments HYPERTHYROIDISM (or thyrotoxicosis) is one of the most common endocrine disorders in geriatric cats, and its diagnosis has steadily increased since the first clinical reports emerged in the late 1970s. At present, it occurs in an estimated two per cent of the feline population. There is no sex or breed predilection (although the disease appears to be less common in Siamese cats), and it is rarely seen in cats below seven years of age. This article discusses feline hyperthyroidism, with reference to the less-common canine form where appropriate. Incidence and cause The most common causes of hyperthyroidism in cats are benign adenomas of the thyroid gland and hyperfunctional adenomatous hyperplasia. Although malignant thyroid tumours do occur, these are rare, accounting for only one to three per cent of all hyperthyroid cats. With a steady increase in the incidence of feline hyperthyroidism over the past 40 years, attention has focused on nutritional and environmental factors as potential underlying aetiologies. Studies have suggested that cats fed canned food show a tendency for hyperthyroidism. This may be associated with plasticiser components such as phthalates and bisphenol A, which leak from the packaging during the sterilising process. Many cat foods (60 per cent) also contain polyphenolic soy isoflavones (genistein and daidzen), which occur in high enough concentrations to interfere 1 / 16

2 with thyroid function. Additional studies have associated the regular application of flea sprays and powders, living indoors and exposure to herbicides, fertilisers and pesticides with a 3.4 to four-fold increased risk of developing hyperthyroidism. Exposure to fire-retardant polybrominated diphenyl ethers used in the manufacture of plastics, computers and upholstery is common, but studies have yet to prove a direct link or mechanism associated with disease development. Thyroid carcinoma is the most common cause of naturally occurring canine hyperthyroidism is thyroid carcinoma, although fewer than 10 per cent of dogs with thyroid carcinomas display signs of hyperthyroidism. Thyroid tumours are usually large and locally invasive, and often metastasise. The Labrador retriever appears to be over-represented and the long-term prognosis is poor. For this breed, iatrogenic hyperthyroidism as a result of over-supplementation has been documented, but rarely causes clinical signs unless in extreme cases of chronic or significant overdosage. Clinical signs Clinical signs occur as a result of the effect of excess thyroid hormones on a variety of organ systems metabolic functions. Since the signs associated with one system may predominate, a diagnosis should not be based on the presence or absence of only one sign. Hypertension and left ventricular hypertrophy often occur secondarily to high levels of thyroxine, but many cats also have concurrent renal or gastrointestinal disease, which may complicate the clinical picture. The most consistent clinical signs are hyperactivity and weight loss, despite an increased appetite. Clinical signs may also include behavioural changes, such as anxiety, vocalisation and aggression. Polydipsia, polyuria, vomiting, excessive grooming, diarrhoea, panting or dyspnoea also occur. Less commonly, cats may present with apathetic hyperthyroidism, in which weight loss is accompanied by lethargy and anorexia. This probably represents an end stage of the disease. Physical findings include cachexia, heart murmur, arrhythmia, an unkempt coat and, occasionally, ventroflexion of the neck. Enlargement of one or both thyroid lobes may be palpable in the ventrolateral cervical region. The majority of hyperthyroid cats demonstrate a greatly reduced tolerance to stress and handling, which should be taken into account during the physical examination. Diagnosis A provisional diagnosis of feline hyperthyroidism can often be reached based on clinical signs and findings alone. However, further investigation is required to confirm the diagnosis, locate the lesion and rule out the presence of concurrent disease. 2 / 16

3 Changes include moderate erythrocytosis and macrocytosis. Alanine aminotransferase and/or serum alkaline phosphatase levels are elevated in more than 90 per cent of hyperthyroid cats. Other changes include hyperphosphataemia and, occasionally, hypokalaemia. Serum biochemistry may identify other conditions, such as renal disease and diabetes mellitus, although it should be remembered that uncontrolled hyperthyroidism can mask renal insufficiency. Baseline serum total T4 (TT4) concentrations measure the amount of protein-bound and free hormones circulating in the blood. In one study, serum T4 concentrations determined in dogs and cats by radio-immune assay, chemiluminescent enzyme immunoassay and an in-house ELISA provided similar and consistent results. The référence range for serum T4 in dogs is usually approximately 13nmol/L to 45nmol/L and 13nmol/L to 50nmol/L in cats. TT4 concentration is often used as the initial screening test for feline hyperthyroidism, and a concentration greater than 50nmol/L is considered diagnostic, assuming clinical signs of disease are also present. A serum T4 concentration less than 25nmol/L rules out hyperthyroidism, except in extremely uncommon situations where severe non-thyroidal illness is present. Serum total T3 is elevated in approximately 75 per cent of hyperthyroid cats. Serum T4 concentrations between 25nmol/L and 50nmol/L do not rule out the early stages of hyperthyroidism, as cats can have a normal serum T4 concentration as a result of random fluctuations or suppression by concurrent disease. Therefore, hyperthyroidism should not be excluded on the basis of one normal T4 test result, especially in a cat with appropriate clinical signs and a palpable nodule. In these cases, the serum TT4 test should be repeated and serumfree T4 measured. Free T4 (ft4), the non-protein bound fraction of T4, accounts for less than one per cent of circulating T4, but it is responsible for the biological effects of the levo form of triiodothyronine (LT3) and regulates the pituitary feedback mechanism. The most accurate test utilises modified equilibrium dialysis (MED) techniques. For most laboratories, the reference range for serum ft4 measured by MED in dogs and cats is approximately 10pmol/L to 45pmol/L and 13pmol/L to 50pmol/L, respectively. Levels above this range are diagnostic for hyperthyroidism. Dynamic tests can be used to distinguish questionable instances from normal cases. In the T3 suppression test, the cat is dosed with L-T3 every eight hours on seven occasions (over 56 hours). Serum TT4 levels are measured within two to four hours of the final dose. A lack of TT4 suppression (greater than 50 per cent of baseline) is considered significant. The thyrotropinreleasing hormone test is of moderate use, although results may be difficult to interpret in cases of non-thyroidal illness. Diagnostic imaging provides one of the most useful tools for the diagnosis of endocrine disorders and multiple modalities are available. Although the thyroid is not usually detectable, radiographs 3 / 16

4 may highlight secondary changes associated with the disease, such as feline hypertrophic cardiomyopathy. Ultrasonography can be used to assess the size and symmetry of the thyroid glands, and is particularly useful in dogs with space-occupying lesions in the cervical region. Retropharyngeal lymph nodes are commonly affected in cases of carcinoma and should also be examined. Ultrasonography alone is often insufficient to determine the margins of large or invasive tumours. In cats, the affected gland s parenchyma often appears somewhat hypoechoic to the surrounding tissue. Cysts can be identified in approximately 10 per cent of cases. Scintigraphy should be performed in dogs with hyperthyroidism, and the thorax screened for ectopic tissue. It should be noted that metastases may fail to take up iodine or pertechnetate and go undetected. Scintigraphy with technetium-99m is the diagnostic imaging method of choice in cats with suspected or confirmed hyperthyroidism, providing information on thyroid function and the presence of ectopic tissue. Based on the results, the clinician can then make an informed decision regarding the most appropriate treatment mode. Treatment Options for thyroid carcinomas in dogs include surgery, chemotherapy, radioactive iodine therapy and radiation therapy. Prognosis depends on the histomorphologic malignancy grade, but also tumour size, invasiveness, metastatic potential and patient condition. Overall, the prognosis for dogs with nonfunctional tumours of the thyroid gland is poor to grave. Treatment options for hyperthyroid cats include medical treatment, surgical removal and radioactive iodine treatment. Treatment response is dependent on organ damage at the time of diagnosis, concurrent illnesses, age at diagnosis and gender. The average survival time for all treatment modalities is reported to be approximately two years. Medical treatment centres around the use of anti-thyroid drugs (methimazole and carbimazole) to reduce the synthesis of T4 and T3. These often achieve euthyroidism within three weeks of treatment, but they do not destroy adenomatous tissue, and relapses will occur within 24 to 72 hours if medication is discontinued. Side effects (such as anorexia, vomiting and lethargy) may be seen in the first weeks of treatment, but are rarely severe enough to warrant the discontinuation of medication. More serious problems, including reduced leucocyte and platelet counts, hepatopathy and skin irritation, are rare, but if they do occur an alternative treatment must be sought. Medication may be given long term, or simply to stabilise the cat prior to surgery. For those cats with concurrent problems, additional medication may be required. The most common of these include?-blockers (atenolol and propranolol) to reduce blood pressure and calcium channel blockers (diltiazem) to slow the heart rate. Cats with renal disease require special consideration. 4 / 16

5 All cats receiving medication should be monitored carefully. Serum biochemistry and haematology should be repeated after three weeks of initiating treatment, and at regular intervals thereafter. Owners should be advised to wear gloves when handling medication and cleaning litter trays used by cats under treatment. For many cats, thyroidectomy is the preferred treatment but, where possible, stabilisation with medical therapy should be undertaken prior to surgical intervention. The surgery is simple and effective, but can be associated with significant morbidity and mortality as patients are often poor anaesthetic and surgical candidates. Complications associated with thyroidectomy include hypoparathyroidism, Horner s syndrome, hypocalcaemia and laryngeal paralysis. Of these, hypocalcaemia as a result of bilateral damage to or removal of the parathyroid glands is the most serious. Following bilateral thyroidectomy, serum calcium concentrations should be measured daily until they are stable within the reference range. Clinical signs associated with hypocalcaemia develop within one to three days of surgery and require treatment with calcium and then vitamin D. Treatment is not required for animals presenting with a low blood concentration of calcium without clinical signs. Following surgery, serum thyroid hormone concentrations should be measured every six to 12 months. Only 30 per cent of hyperthyroid cats have unilateral disease. These cats benefit from hemithyroidectomy, but adenomatous changes will develop in the normal thyroid lobe, although this may take several years. Cats with bilateral adenomas require the removal of both lobes, with the preservation of parathyroid glands. At the time of surgery, both lobes are usually enlarged although approximately 15 per cent of these cats have one lobe that is only slightly enlarged or of normal size. If pre-operative thyroid imaging is not possible, the obviously enlarged lobe should be removed and owners advised that removal of the contralateral lobe would be required at a later date when the hyperthyroidism returns. Serum calcium levels are often reduced transiently following thyroidectomy, even when the parathyroid glands appear to have been preserved. For this reason, when bilateral disease is apparent, many veterinarians prefer to remove the lobes separately six to eight weeks apart, allowing the recovery of normal parathyroid hormone production in between procedures. Radioactive iodine (radioiodine L131) is an effective and safe treatment for cats with hyperthyroidism, and does not require anaesthesia. Radioiodine is concentrated in the abnormal thyroid cells, where it destroys the hyper-functioning tissue. Normal cells receive only a small radiation dose and are rarely affected to any degree. Radioiodine is the best treatment when nuclear medicine facilities are available. A single L131 treatment will restore euthyroidism in 95 per cent of cats. Those cats that remain persistently hyperthyroid can be successfully retreated with radioiodine. Hypothyroidism may occur 5 / 16

6 occasionally; when clinical signs are apparent, thyroxine supplements may be required. Untoward systemic effects have not been observed and anaesthesia is not required. However, the cat must be hospitalised for three to six weeks until radiation levels have fallen to acceptable limits. Licensed facilities in the UK are located at the Animal Health Trust near Newmarket, the universities at Bristol, London and Glasgow, the Barton Veterinary Hospital in Canterbury, the Cardiff Cat Clinic and the Bishopton Veterinary Group in Ripon, North Yorkshire. Cases of thyroid adenocarcinoma are rare and more difficult to manage, but they can be treated using very high doses of radioactive iodine. Only the University of Bristol is licensed to administer doses this high. Successful treatment of hyperthyroidism in cats may unmask pre-existing renal dysfunction. This is because excessive thyroid hormone concentrations lead to increased cardiac output, increased renal blood flow and intrarenal arteriolar dilatation, resulting in a higher glomerular filtration rate (GFR) and lower blood urea nitrogen and creatinine levels. Following reversal of the hyperthyroidism, the GFR drops and azotaemia may become evident. For this reason, hyperthyroid patients with known renal insufficiency should be treated medically, rather than undergo an irreversible procedure such as thyroidectomy or radioiodine treatment. Should signs of renal impairment develop during therapy, it may be preferable to maintain these cats in a mild state of hyperthyroidism. Summary Feline hyperthyroidism presents a diagnostic and therapeutic challenge, and ongoing studies are in progress to further our understanding of disease aetiology, diagnosis and treatment. Work is underway to develop a commercial feline TSH assay with similar sensitivity to the test used in dogs. Additional studies, examining the measurement of serum thyroglobulins (used in human medicine to detect and monitor the presence of thyroid tumours), show promise for the early diagnosis of hyperthyroidism. References are available upon request to the editor. 6 / 16

7 Only 30 per cent of hyperthyroid cats have unilateral disease. These cats benefit from hemithyroidectomy. However, adenomatous changes will develop in the normal thyroid lobe, although this may take several years. 7 / 16

8 Side effects (anorexia, vomiting, lethargy) are rarely severe enough to warrant the discontinuation of medication. More serious problems include reduced leucocyte and platelet counts, hepatopathy, and skin irritation(pictured). 8 / 16

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10 Hyperthyroidism occurs in an estimated two per cent of the feline population. There is no sex or breed predilection (although the disease appears less commonly in Siamese cats) and it is rarely seen in cats below seven years of age. 10 / 16

11 Left: cats may present with apathetic hyperthyroidism, in which weight loss is accompanied by lethargy and anorexia. This probably represents an end-stage of the disease. 11 / 16

12 Right: physical findings include cachexia, heart murmur, arrhythmia, unkempt coat and ventroflexion of the neck. 12 / 16

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14 Left: the majority of hyperthyroid cats demonstrate a greatly reduced tolerance to stress and handling, which should be taken into account during the physical examination. 14 / 16

Right: the most common cause of naturally occurring canine hyperthyroidism is thyroid carcinoma, although fewer than 10 per cent of dogs with thyroid

15 Right: the most common cause of naturally occurring canine hyperthyroidism is thyroid carcinoma, although fewer than 10 per cent of dogs with thyroid carcinomas display signs of hyperthyroidism. The Labrador retriever appears to be over-represented and the long-term prognosis is poor for this breed. 15 / 16

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Causes and management of hyperthyroidism in cats

Vet Times The website for the veterinary profession https://www.vettimes.co.uk Causes and management of hyperthyroidism in cats Author : Emma Garnett Categories : RVNs Date : May 1, 2008 Emma Garnett VN,