Abstract: Background – Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Metabolomic data for hyperthyroid cats is lacking.
Hypothesis/Objectives – To identify metabolomic signatures in hyperthyroid cats pre- and post-I131 therapy and identify persistent metabolic changes.
Animals – Privately-owned hyperthyroid cats (n = 7) admitted for I-131 treatment and euthyroid privately-owned control (CON) cats (n = 12).
Methods – Prospective case-control study. Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy. Untargeted metabolomic analysis was performed, and data were analyzed with MetaboAnalyst software (Figure 1).
Results – Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis (Figure 2A&B) revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Random forest analysis disclosed thyroxine as the best model discriminator (Figure 2C), with the lipids 1-pentadecanoyl-GPC and mevalonate following. Median serotonin levels were higher in hyperthyroid cats (Figure 2D). Carnitine and alpha-tocopherol levels were lower (T0 vs. CON), persisting after I-131 treatment (Figure 2D).
Conclusions and clinical importance – Metabolic derangements do not completely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine if the persistent metabolic alterations demonstrated here could be a therapeutic target in treated hyperthyroid cats.