Hyperthyroidism is reported as the most commonly diagnosed endocrinopathy in older cats [1]. The prevalence of hyperthyroidism in older cats was reported between 3.93% and 21.1% in many countries [2-6]. Feline hyperthyroid patients had elevated levels of thyroid hormone accompanied with one or more lobe of thyroid gland hyperplasia or adenoma [7]. Because thyroid hormone involved in various metabolic controls, its excessiveness induces clinical signs such as weight loss, gastrointestinal sign, hyperactivity, and tachycardia [1,7,8]. Because of its pathogenesis is unclear, the goal of treatment is controlling excessive thyroid hormone which affect systemic metabolic status [1,7,8].

The treatment options include administration of antithyroid drugs, surgical thyroidectomy, and radioiodine therapy (RAIT) [1,7,8]. Regardless of its disadvantages, such as restriction of facilities or permission of using isotopes, the RAIT is considered as an optimal treatment option for feline hyperthyroid cats [8,9]. To maximize therapeutic effect and avoid adverse effect such as iatrogenic hypothyroidism, several ideal dosing protocols of the RAIT was reported in veterinary field [9-12]. However, RAIT for feline hyperthyroidism has not yet been investigated in South Korea. Therefore, this preliminary study describes the efficacy and the safety of the RAIT using locally produced radioiodine (RAI) in South Korea through demonstrating clinical features of 10 hyperthyroid cats in pre- and post-treatment.

This study evaluated the clinical efficacy of the RAIT in 10 hyperthyroid cats. Disappearance of the clinical signs, significant decrease in serum tT4 and liver enzymes were identified within 9 days after the RAIT. There were no significant differences in serum level of BUN, creatinine, SDMA, hematocrits and WBC counts between pre- and post-treatment. These results present that the RAIT is safe and effective treatment for hyperthyroid cats.

Within the current cases, the clinical findings of the hyperthyroid cats had no unexpected features and they were similar with the results of the previous studies [7,17,18]. Feline hyperthyroidism is the most common endocrine disorder in middle to old aged cats and its prevalence is up to 10% with cats older than 10 years [1]. In these cases, hyperthyroid cats were 8.5% of total cats that have visited our clinic and 8 of 10 RAI treated hyperthyroid cats were aged over 10 years. Therefore, the prevalence may increase if they were grouped by the age of cat over than 10 years from the whole population. The most common clinical signs of 10 hyperthyroid cats were weight loss, polyuria/polydipsia, tachycardia, and vomiting; however, tachycardia could be over-estimated because of white-coat effect [19]. Additionally, numerous studies have suggested that purebred cats, such as Siamese and Himalayan, were associated with lower prevalence than domestic short- and long-haired cats [17,20,21]. Similarly, domestic short hair was 40% of 10 hyperthyroid cats, but purebred of Siamese and Himalayan was not identified in this study. Moreover, purebred of Russian blue was 40% of the total, either. In one statistical survey of Korea in 2021, the most common bred cat was domestic short hair (45.2%), followed by Russian blue (19.0%) and Persian (18.7%) [22]. Despite the breeding percentage, Russian blue had a similar prevalence to domestic short hair but a higher prevalence than Persian. This finding suggests that the high prevalence of Russian blue may have different etiology, not because of its population. The etiology for feline hyperthyroidism is still unclear but some studies have reported environmental suspicions such as canned food or phthalates which is goitrogenic compounds [17,20,23]. However, evaluation of the association between environmental factors and hyperthyroidism was difficult in the current study because of its small sample size. For the evaluation of the variable risk factors associated with etiology of feline hyperthyroidism, further studies of larger population are needed.

In a previous study, the response to the RAIT using scoring system had rapid response with 84.7% of cats having tT4 within or below the reference range by the time at hospital discharge and tT4 was within or below the reference range in 98.5% of cats after 6 months [9]. In another study, the cure rate of > 97% with reduced frequency of side effect (e.g. iatrogenic hypothyroidism and azotemia) was reported in low-dose (2 mCi) RAI treatment for mild-to-moderate hyperthyroid cats [10]. All of 10 cats had decreased tT4 after the RAIT, but 4 of 10 cats (ID 1, 2, 6, and 8) were retreated at 3 months after the first RAIT, because the tT4 was maintained above than the normal (serum tT4 ≥ 4 μg/dL). These 2 (ID 1, 8) of 4 retreated cats had fixed low-dose RAIT based on the initial tT4 at the first time, but the therapeutic effect was insufficient because actual concentration of initial tT4 was above 13 μg/dL. Some studies reported the differences of tT4 concentration with measurement methods [24,25]. Initial tT4 concentration of these cats might have been suppressed due to transient non-thyroidal illness or laboratory differences which can influence errors [24-26]. The other cat (ID 2) had fixed low-dose RAI at the first RAIT because of its accompanied cardiomyopathy. The cardiopulmonary dysfunction can be caused by thyroid storm, and it is resulted from a sudden release of thyroid hormones by administered radioiodine that immediately destroys hyperactive thyroid cells [27]. Three months after, the cat was retreated by scoring system that confirmed a lower score than before, and cured completely after the second RAIT. The last cat (ID 6) had insufficient treatment response even though the injected dose was optimized by the scoring system. Because the cat had ectopic thyroid tissues and relatively large thyroid gland, it was suspected as thyroid carcinoma but was not differentiated through a histopathology because of the owner's disagreement of thyroid biopsy. Three months after the second RAIT, serum tT4 level was identified as 3.5 μg/dL. By these all cases, various doses of RAI between 2 and 5 mCi were administered in the initial treatment, and the treatment efficacy differed according to disease severity. Furthermore, the superiority of therapeutic effect between the scoring system and fixed low-dose treatment was not identified. Inappropriate RAI application can reduce the therapeutic effect, while administering an overdose of RAI may lead to iatrogenic adverse effects such as hypothyroidism. Therefore, accurate evaluation of disease severity is necessary for determining the appropriate dose, and further study involving statistical analysis of various parameters such dosage, disease severity, and treatment outcomes should be needed.

The aim of the RAIT is to achieve euthyroid through single dose of the RAI application without producing hypothyroidism [9]. The most common adverse effect of the RAIT was iatrogenic hypothyroidism and concurrent chronic kidney disease which is masked due to hyperthyroidism [9,28]. Currently, iatrogenic hypothyroidism of the RAI treated cats was reported 25 % to 50% in most studies of the RAI treatment protocols [10,29,30]. In these case series, one cat (ID 3) was confirmed serum tT4 concentration below 0.9 μg/dL at 1 month after the RAIT, but maintained subclinical state during the monitoring period. Thyroid function can be degraded by the destruction of hyperactive thyroid cells by the RAI, but could be recovered normally as restoration of suppressed normal thyroid cells by thyroid stimulating hormone increasement [9]. Additionally, in one cat (ID 7), the serum creatinine level was increased from 1.9 mg/dL to 2.1 mg/dL at 6 months after the RAIT in accordance with the normalization of thyroid hormone. Thyroid hormone can be reduced gradually during 6 months, and the glomerular filtration rate may also be decreased concurrently [9]. Thus, the serum levels of thyroid hormone and creatinine should be monitored together periodically.

In this study, a significant decrease in ALT and ALP along with serum tT4 level was identified in post-RAIT. Liver functions and enzymes can be affected by several mechanisms, but its etiology is not fully understood yet [31]. First, elevated thyroid hormone can affect increase in liver enzymes because liver is associated with synthesis and metabolism of thyroid hormones [31]. Thyrotoxicosis can increase local and systemic metabolism and oxygen requirement that leads to relative hypoxic damage of hepatocyte [32-34]. Additionally, elevated serum bone ALP isoenzyme which is affected by thyroid hormone may contribute to serum ALP elevation [35,36]. A previous study reported that hyperthyroid cats, even with severely high level of liver enzymes, had a normal liver function and the serum activity of liver-derived enzymes returned to normal at 6 weeks after successful treatment with the RAI [31]. Also, this study supports the finding of previous studies by identifying decreased liver-derived enzyme levels due to decreased serum tT4 concentration in a shorter period than those reported before.

There were some limitations in these case series. First, small number of hyperthyroid cats were enrolled, which might not represent the entire population of cats with the RAIT. Second, comparison of clinical data between pre- and post-treatment was done with short term period, and it may not reflect the long-term outcome. Third, only 2 dosing methods were used in these cases, and it was hard to compare with other novel dosing methods, such as using algorithm or other fixed dose method, that have been reported recently [12,30,37]. Additionally, differences in treatment efficacy based on the underlying cause of hyperthyroidism, such as thyroid malignancy, could not be confirmed because histopathologic diagnosis through thyroid biopsies were unable to be performed on all cats. Therefore, additional studies should be performed to compare the effectiveness of treatment in the various underlying conditions of feline hyperthyroidism.

In conclusion, this preliminary study marks the first investigation of RAIT for feline hyperthyroidism in South Korea, using locally manufactured RAI. The treatment efficacy varies depending on the severity of disease, while the safety of RAI doses ranging from 2 to 5 mCi in the initial treatment was investigated. To ensure the adequate therapeutic effect and avoid iatrogenic adverse effect, it will be necessary to determine the RAI dose based on the severity of the disease. Based on these findings, the RAIT could be considered the treatment option and prevent adverse effects from medication or surgery in hyperthyroid cats.