Assessment of treatment outcomes and symmetric dimethylarginine in hyperthyroid cats treated with a fixed dose of radioiodine

Background: Hyperthyroidism and chronic kidney disease (CKD) are common in geriatric cats and often occur concurrently. Among other effects, hyperthyroidism causes protein catabolism and increases renal blood flow and the glomerular filtration rate (GFR). These effects render traditional renal markers insensitive for the detection of CKD in cats with uncontrolled hyperthyroidism. Early identification of occult CKD may influence the prognosis, monitoring and therapy of hyperthyroidism or CKD. Symmetric dimethylarginine (SDMA) is a new serum renal biomarker that is stable, easily measured and has been recently validated for use in cats. SDMA correlates well with GFR and is not affected by muscle mass. SDMA is more sensitive than serum creatinine in detecting early CKD in non-hyperthyroid cats, but our understanding of its performance in hyperthyroid cats is in its infancy. In Australia, the gold standard treatment for cats with benign hyperthyroidism (i.e. thyroid hyperplasia or adenoma) is a fixed dose of orally administered radioiodine, regardless of the serum total thyroxine (TT4) concentration at the time of diagnosis. The development of iatrogenic hypothyroidism after radioiodine treatment is detrimental to renal function and may negatively affect long-term survival. As a result, the goal of radioiodine treatment is to maximise the number of cats that achieve euthyroidism while limiting the development of hypothyroidism. Currently, information regarding long-term outcomes in cats treated with an oral fixed dose of radioiodine is limited and there are no practical markers to detect occult CKD in these cats. Objectives: This study aimed to describe the treatment outcomes following oral administration of a fixed dose (138 MBq; 3.7 mCi) of radioiodine in a sample of hyperthyroid cats and examine the correlation between serum TT4 concentrations before and after treatment. A second aim was to measure the serum SDMA concentration in hyperthyroid cats before and after treatment to determine the relationships between SDMA, creatinine and TT4 concentrations at both time points. Method: In a sample of cats previously treated with a fixed dose of oral radioiodine, TT4 concentration and renal clinical pathological parameters were documented before and after radioiodine treatment. Logistic regression was used to assess the relationship between TT4 concentrations before and after treatment. The differences in pre- and post-treatment variables for cats that had TT4 concentrations below or within the reference interval were also assessed. Renal parameters including urine specific gravity and serum SDMA, urea and creatinine concentrations were measured before and three months after receiving a fixed dose of oral radioiodine treatment in prospectively enrolled hyperthyroid cats. The Pearson correlation coefficient was used to determine the association between treatment and serum TT4, SDMA and creatinine concentrations. To assess agreement between serum SDMA and serum creatinine regarding categorisation of CKD staging, Goodman and Kruskal’s gamma statistic was used. Results: Of 162 cats, 133 (82%) had TT4 concentrations within the reference interval after treatment. Four (3%) and 25 (15%) cats had TT4 concentrations above and below the reference interval after treatment, respectively. The severity of hyperthyroidism at diagnosis, as measured by the percentage elevation of TT4 concentration above the reference interval, had no impact on the odds of cats having TT4 concentrations below the reference interval after treatment (OR = 1.00; 95% CI 0.96–1.05; p = 0.93). Over the follow-up period after radioiodine treatment, serum SDMA increased in 51 of 74 (69%) cats, whereas serum creatinine increased in 78 of 80 (98%) cats. A moderate correlation between serum SDMA and creatinine was seen after treatment (r = 0.523, p < 0.001) but not before treatment (r = 0.523, p = 0.23). Where assessable after treatment, serum SDMA and creatinine did not agree in the staging of cats with kidney dysfunction based on the International Renal Interest Society CKD guidelines. No significant correlation was seen between serum SDMA and TT4 concentration at any time point. Conclusions and relevance: When using an orally administered fixed dose of radioiodine for the treatment of feline hyperthyroidism, TT4 concentrations at diagnosis cannot be used to predict TT4 concentrations after treatment. The proportion of cats with TT4 concentrations below the reference interval after treatment was 15%. Further work is required to optimise oral radioiodine dosing to maximise euthyroidism. Extra-renal factors associated with hyperthyroidism appear to hinder the ability of SDMA to identify cats with occult CKD before treatment. Further work is required to elucidate the mechanism and impact on the performance of SDMA as a diagnostic test of renal function in hyperthyroid cats.