Radioactive iodine (RAI) treatment for feline hyperthyroidism

FeAtuRe ARtICle

Radioactive iodine (RAI) treatment for feline hyperthyroidism

JINg-lu teH, BVM&s, MRCVs

Introduction

Feline hyperthyroidism (FHt) is currently the most diagnosed endocrine disease among cats worldwide (Carney et al. 2016; Peterson 2020). until the exact cause is determined, and prevention becomes possible, the prevalence of FHt is likely to increase (Rijnberk and Kooistra 2010a; Carney et al. 2016; Peterson 2020). FHt arises most frequently from adenomatous hyperplasia, rarely malignant carcinoma and results in deleterious effects on kidney, heart, gastrointestinal tract and systemic blood pressure (Rijnberk and Kooistra 2010a; Carney et al. 2016; Peterson 2020). With proper treatment and monitoring hyperthyroid cats can be cured or controlled; and live >2 years (Carney et al. 2016; Peterson 2020). Currently there are four treatment methods available: radioiodine (RAI), thyroidectomy, medical management (e.g. methimazole) and dietary management (Rijnberk and Kooistra 2010a; Carney et al. 2016; Peterson 2020). this article focuses on RAI, now widely considered as the gold standard treatment and discusses its pros, cons, pre- and post-treatment management. targeted ablation of the abnormal thyroid tissue is achieved via selective uptake and concentration of I-131 by the hyperfunctional thyroid tissue (Peterson 2020). Normal or atrophied thyroid tissue does not absorb I-131 as much as the hyperactive thyroid tissue thus remains unaffected (Rijnberk and Kooistra 2010).

pros and efficacy of radioactive iodine treatment

Radioactive iodine treatment has a high cure rate (85–95%) (Slater et al. 1994; Rijnberk and Kooistra 2010a; Volckaert et al. 2016; Peterson 2020). In most cases the concentration of serum total t4 (tt4) reduced significantly within 1 month and continued to reduce gradually up to 6 months post-treatment (Mooney 2005; Peterson 2006). Successfully RAI-treated cats lived a median of 4 years after treatment, twice as long compared to cats undergoing methimazole treatment (Milner et al. 2006; Rijnberk and Kooistra 2010a). RAI targets specifically hyperfunctional thyroid tissue while sparing the surrounding healthy tissue (Peterson 2006; Rijnberk and Kooistra 2010a; Carney et al. 2016). It is more efficacious than surgery in treating ectopic thyroid, which was reported in 3.9–23% of hyperthyroid cats (Mullowney et al. 2021). RAI is a simple, anaesthesia-sparing procedure, administered by injection or orally (Carney et al. 2016; Peterson 2020).

Contact: Chatswood Vet Clinic Willoughby, NSW, Australia. j.l.teh83@gmail.com

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The cons and side effects of radioactive iodine treatment

Radioactive iodine has a higher upfront but lower longterm cost compared to other treatment (Carney et al. 2016; Peterson 2020). RAI may not be easily accessible in some areas as the procedure must be carried out at a licensed facility (Peterson 2006, 2020). the requirement for hospitalisation post-treatment may be stressful for some cats and owners (Peterson 2020). After treatment, clients need to adhere to regional rules and regulation to minimise human exposure to radiation (Mooney 2005; Rijnberk and Kooistra 2010a; Peterson 2020). transient fever and dysphagia have occasionally been reported soon after treatment (Peterson 2006, 2020). Cases of iatrogenic hypothyroidism post-treatment have been reported when a standard high fixed-dose protocol (4–5 mCi) was used frequently in the past (Lucy et al. 2017). the incidence

is now reduced due to the preference for individualised, lower dosage protocol (3–5 mci) based on the tt4 concentration and the thyroid volume (Lucy et al. 2017; Peterson 2020).

patient selection

All hyperthyroid cats should be screened for any cardiorespiratory, renal, gastrointestinal, or neoplastic illness prior RAI treatment because comorbidities have a great impact on survival time regardless of the treatment methods for FHt (Carney et al. 2016; Peterson 2020). the most suitable candidate is expected to live >3 years and is free of comorbidities (Peterson 2020). one should be aware that it is not possible to distinguish hypertrophic cardiomyopathy from hyperthyroidrelated cardiomyopathy until cats have been euthyroid for 3–6 months (Carney et al. 2016). Palliative care should be considered for cats with moderate to severe comorbidities especially chronic kidney disease (CKD) (Peterson 2006, 2020). Cats with mild or stable CKD without other comorbidities can still be considered a candidate with careful consideration of RAI dosage to avoid iatrogenic hypothyroidism (Peterson 2006, 2020).

post-RAI monitoring

All RAI-treated patients should be followed up long-term for the best outcome. Monitoring during the first 6 months after treatment is to identify any hypothyroidism, CKD or treatment failure. Subsequent yearly monitoring is to check for relapse or development of hypothyroidism (Carney et al. 2016; Peterson 2020).

Chronic kidney disease

A patient’s renal status after RAI treatment is critical due to the lack of reliable markers to identify pre-existing CKD in the presence of FHt (Peterson et al. 2018; DeMonaco et al. 2020; Peterson 2020; Yu et al. 2020). Azotemia can be masked by combination of increased glomerular filtration rate (GFR) and decreased body mass in FHt (Peterson et al. 2018). there is also confounding effect on interpretation of urine specific gravity (uSG) due to thyrotoxicosis-induced psychogenic polydipsia or acquired nephrogenic diabetes insipidus (Mooney 2005; Rijnberk and Kooistra 2010a). While symmetric dimethylarginine (SDMA) has been shown to be better than creatinine as a marker for renal function in healthy cats and cats with CKD, this was not the case for cats with FHt (Buresova et al. 2019; DeMonaco et al. 2020). one study showed that elevated concentrations of SDMA pre-treatment has high specificity (97.7%) but poor sensitivity (33.3%) for predicting development of azotaemia after RAI treatment (DeMonaco et al. 2020). Another study demonstrated SDMA was not a reliable renal marker in assessing renal function after RAI treatment due to poor correlation with GFR (Buresova et al. 2019). In contrast, both the creatinine and uSG correlated better with GFR after RAI treatment (Buresova et al. 2019). the trend of SDMA pre- and post-treatment was inconsistent with other renal markers and CKD stages (DeMonaco et al. 2020). Hence, SDMA should be interpreted along with concentrations of creatinine, urea and uSG; with consideration of physiological factors, breed variation and thyroid status (Yu et al. 2020). GFR shows most significant changes within 1 month of a cat becoming euthyroid; minimal changes from 1–6 months and no changes beyond 6 months (Peterson 2006). the most reliable time to assess kidney status would arguably be 3–6 months after the cat becomes euthyroid (Peterson 2020). Between 14–25% of RAI-treated cats became azotemic within 6 months of treatment (Slater et al. 1994; Milner et al. 2006; Peterson 2020). Hypothyroidism

twenty percent of cats that receive either RAI or methimazole treatment developed hypothyroidism (Peterson 2006; Aldridge et al. 2015; Carney et al. 2016). this maybe an underestimate given that not all cats in these studies were monitored long term and that subclinical hypothyroidism maybe overlooked (Williams et al. 2010; Aldridge et al. 2015; Peterson 2020). In the study by Williams et al. (2010), the hypothyroid cats had a higher incidence of azotemia compared to the euthyroid group. of 255 RAI-treated cats followed long-term, by Slater et al. (1994), 27% had concurrent hypothyroid and CKD. Hypothyroid cats with azotemia survived half as long as hypothyroid cats without azotemia (456 vs. 905 days) (Williams et al. 2010). In the euthyroid group, the survival time between azotemic and non-azotemic cats were not significantly different thus suggesting hypothyroidism may be contributing to progression of CKD and is thus a negative prognostic indicator in azotemic cats. In this population, 68% of hypothyroid cats (tt4 <10 nmol/L) had high tSH concentrations (>0.15 ng/ mL) detected within 6 months after RAI treatment. the exact time taken for tSH suppression to be reversed after cats become euthyroid is currently unknown (Williams et al. 2010). tSH concentration could potentially be low or normal in hypothyroid cats at early stages (Aldridge et al. 2015). to avoid iatrogenic hypothyroidism, the ideal recommended tt4 concentration post-RAI treatment is

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in the middle of the reference interval (Williams et al. 2010; Peterson 2020). For cats with decompensated renal disease following RAI treatment, it is imperative to identify iatrogenic hypothyroidism promptly because L-thyroxine supplementation can potentially halt the progression and improve survival (Peterson 2006; Aldridge et al. 2015).

treatment failure

thyroid carcinoma is often the reason for treatment failure (Harvey et al. 2009; Peterson 2020; Mullowney et al. 2021). one study found cats with tt4 concentration >150 nmol/L at discharge following RAI treatment were more likely to fail to become euthyroid and 86% of cats became euthyroid with a second RAI treatment (Mullowney et al. 2021). With high I-131 dosage, RAI can potentially cure thyroid carcinoma (Peterson 2006; Harvey et al. 2009; Mullowney et al. 2021). the prevalence of thyroid carcinoma has been reported to be 0.5–3 % (Harvey et al. 2009; Rijnberk and Kooistra 2010a; Peterson 2020; Mullowney et al. 2021). this could be an underestimate due to difficulty in diagnosis: scintigraphy cannot distinguish benign from malignant features in 100% of cases and histology is not always conclusive (Harvey et al. 2009). Compared to canine thyroid carcinoma, there is a low rate of metastasis in cats (Harvey et al. 2009; Rijnberk and Kooistra 2010a; Peterson and Broome 2015).

Conclusion

Successful RAI treatment offers definitive cure for FHt with significant improvement in quality of life and survival time (Peterson 2006; Rijnberk and Kooistra 2010a; Peterson 2020). Critical selection of patients; appropriate RAI dosage; and monitoring for any azotemia, hypothyroid, treatment failure or relapse post-treatment are important parts of management.

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this review was written as part of the requirements for completing the Master of Veterinary Medicine programme at Massey university.