Carmel T. Mooney, MVB, MPhil, PhD, DECVIM-CA, MRCVS
Department of Small Animal Clinical Studies, School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland
Hyperthyroidism remains the most common endocrine disease in cats, with a prevalence of 10% or more in older cats presenting to first-opinion veterinary practices. The aetiology remains unclear, and although several risk factors have been associated with the disease, none are definitive and therefore prevention is not possible. Benign adenomatous hyperplasia or adenoma of one or more commonly both thyroid lobes is the most common lesion within affected thyroid tissue and at least initially, the prognosis is good with effective therapy. Palliative treatment options consist of control of thyroid hormone production through administration of the antithyroid drugs or alternatively through feeding an iodine-restricted food. Curative options include removal of affected thyroid tissue surgically or destruction through the use of radioactive iodine. Most endocrinologists consider radioactive iodine as being the gold standard treatment method. However, it is not always available and may not be suitable for all hyperthyroid cats. Most commonly, a treatment choice is individualised for each cat taking into consideration the advantages and disadvantages of each, severity of the illness, facilities and expertise available, cost and owner choice.
Hyperthyroidism is a disease of older cats, and it is not unexpected that a proportion of cats present with concurrent non-thyroidal illness. Hyperthyroid cats with pre-existing azotaemia have a reduced survival time. However, many cats do not have azotaemia prior to treatment but develop it after induction of euthyroidism.1 All treatment options can result in unmasking of kidney disease. Predicting those cats that will develop post-treatment azotaemia is difficult, but there is some evidence that measurement of serum SDMA concentrations and urine specific gravity may be useful in predicting its occurrence.2 Development of azotaemia post treatment does not apparently affect survival.3 However, there is some evidence that development of hypothyroidism can be detrimental to kidney function and may adversely affect survival.4
Methimazole and carbimazole are the two antithyroid drugs most frequently used for preoperative and long-term medical management of hyperthyroidism because of their consistent and potent effect in lowering thyroid hormone concentrations and relatively limited occurrence of serious adverse effects. Both are actively concentrated by the thyroid gland where they inhibit thyroid hormone production. Carbimazole is converted to methimazole and only methimazole accumulates in the thyroid gland. Methimazole is available as both human and veterinary licensed formulations (Felimazole® [1.25, 2.5 and 5 mg], Dechra Veterinary Products; Thiafeline® [2.5 and 5 mg], Animalcare; Thyronorm® [5 mg/mL liquid], Norbrook). Carbimazole is also available as a preparation for human use, and a novel once-daily controlled-release formulation (10- or 15-mg tablets) is licensed for cats in Europe (Vidalta® [10 and 15 mg], MSD Animal Health). Administration with food significantly enhances absorption. For long-term management, once euthyroidism has been achieved, the daily dosage is adjusted, aiming for the lowest possible dose that effectively maintains control.
Long-term monitoring of cats involves regular assessment of clinical signs and serum total T4 measurements every 3 to 6 months with reassessment of total T4 concentration 10 days to 3 weeks after each dose adjustment. Whether antithyroid medication is given once or twice daily has little impact on the timing of samples for monitoring purposes.5 It is generally accepted that total T4 concentration should be maintained within the lower end of the reference interval.6 In many cats, antithyroid drug therapy results in serum total T4 concentrations below the reference interval.
Although overt clinical signs of hypothyroidism rarely develop, and surgical risks are not increased, hypothyroidism should be avoided because if its detrimental effect on kidney function. Compliance with oral medication can be problematic in fractious or inappetent cats. Drug absorption is also potentially affected by concurrent gastrointestinal disease, particularly for those cats that vomit. Methimazole and carbimazole can be reformulated for transdermal application and appear equally as efficacious as oral preparations.7 Recommendations for starting doses and follow-up adjustments are similar for transdermal and oral administration. There are few commercially available transdermal products. Custom formulation increases expense of therapy, and stability of the product is not guaranteed. There are health concerns regarding exposure of humans to methimazole.
There is growing evidence that medical therapy may not be as efficacious in the long term. Persistent hyperthyroidism, recurrent hyperthyroidism, increasing difficulty in controlling hyperthyroidism despite increasing drug dosages, and a yo-yo effect between hypothyroidism and hyperthyroidism appear to be common over time.
Continuing efficacy of antithyroid medication is highly dependent on good owner and cat compliance, and this can be difficult to maintain over prolonged periods. Importantly, medical management does not address the underlying cause of hyperthyroidism, and over time the pathological changes in the thyroid gland progress and the prevalence of extreme goitre, multifocal lesions, intrathoracic thyroid masses and suspected malignant transformation increase.8 Lack of efficacy long term should be considered as a disadvantage of oral/transdermal medication.
Restricted Iodine Diets
A restricted iodine diet has been marketed for optimising thyroid health (Hill’s y/d). Exclusively feeding this diet has been shown to normalize thyroid hormone concentrations in some affected animals but usually only in mildly affected cases.9 However, clinical signs may not fully reverse, suggestive of persistent hyperthyroidism throughout treatment, and the time to develop euthyroidism can be prolonged. There appear to be issues of compliance that may be related to palatability. In cats where other treatments are refused or not feasible, it may be a useful option. Other food sources must not be available.
In practice, surgical thyroidectomy is often considered a treatment of choice, particularly if radioactive iodine is unavailable. The majority (>70%) of cats require bilateral thyroidectomy. If a unilateral thyroidectomy is carried out, future monitoring for recurrence of the condition is required. Routine bilateral thyroidectomy, whilst increasing the risk of postoperative complications, obviates the need for decision-making at the time of surgery. However, ectopic thyroid tissue should be considered if hyperthyroidism persists after routine thyroidectomy. A major concern is the development of postoperative hypocalcaemia that occurs within 1 to 5 days of surgery. It is difficult to accurately assign a risk for hypocalcaemia in a cat undergoing bilateral thyroidectomy, as it is highly surgeon dependent. However, with experience, a low rate of postoperative hypocalcaemia (<10%) and recurrence (5%) is expected. As for medical treatment, regular postoperative monitoring is required to ensure that permanent hypothyroidism does not develop.
Assessment for Hypothyroidism
Irrespective of treatment modality, hypothyroidism is a potential sequela. Although no strict rules exist, suppressed total T4 values should prompt consideration of further investigation for hypothyroidism. Alternatively, it is probably best practice to monitor cats through measurement of total T4 and TSH, as it appears that TSH concentrations more accurately reflect reduced thyroid function.10 Given that high TSH values are expected, use of the canine assay is considered reasonable. A low total T4 and high TSH should be interpreted as indicating hypothyroidism and managed by decreasing the antithyroid drug dosage or implementing L-thyroxine supplementation. Reference interval total T4 concentrations with high TSH may also represent reduced thyroid function and should be carefully monitored, particularly if azotaemic.
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