Expected total thyroxine (TT4) concentrations and outlier values in 531,765 cats in the United States (2014–2015)

Background: Levels exceeding the standard reference interval (RI) for total thyroxine (TT4) concentrations are diagnostic for hyperthyroidism, however some hyperthyroid cats have TT4 values within the RI. Determining outlier TT4 concentrations should aid practitioners in identification of hyperthyroidism. The objective of this study was to determine the expected distribution of TT4 concentration using a large population of cats (531,765) of unknown health status to identify unexpected TT4 concentrations (outlier), and determine whether this concentration changes with age. Methodology/Principle findings: This study is a population-based, retrospective study evaluating an electronic database of laboratory results to identify unique TT4 measurement between January 2014 and July 2015. An expected distribution of TT4 concentrations was determined using a large population of cats (531,765) of unknown health status, and this in turn was used to identify unexpected TT4 concentrations (outlier) and determine whether this concentration changes with age. All cats between the age of 1 and 9 years (n = 141,294) had the same expected distribution of TT4 concentration (0.5–3.5ug/dL), and cats with a TT4 value >3.5ug/dL were determined to be unexpected outliers. There was a steep and progressive rise in both the total number and percentage of statistical outliers in the feline population as a function of age. The greatest acceleration in the percentage of outliers occurred between the age of 7 and 14 years, which was up to 4.6 times the rate seen between the age of 3 and 7 years. Conclusions: TT4 concentrations >3.5ug/dL represent outliers from the expected distribution of TT4 concentration. Furthermore, age has a strong influence on the proportion of cats. These findings suggest that patients with TT4 concentrations >3.5ug/dL should be more closely evaluated for hyperthyroidism, particularly between the ages of 7 and 14 years. This finding may aid clinicians in earlier identification of hyperthyroidism in at-risk patients.