Metabolomic Abnormalities in Serum from Untreated and Treated Dogs with Hyper- and Hypoadrenocorticism

The adrenal glands play a major role in metabolic processes, and both excess and insufficient serum cortisol concentrations can lead to serious metabolic consequences. Hyper- and hypoadrenocorticism represent a diagnostic and therapeutic challenge. Serum samples from dogs with untreated hyperadrenocorticism (n = 27), hyperadrenocorticism undergoing treatment (n = 28), as well as with untreated (n = 35) and treated hypoadrenocorticism (n = 23) were analyzed and compared to apparently healthy dogs (n = 40). A validated targeted proton nuclear magnetic resonance ((1)H NMR) platform was used to quantify 123 parameters. Principal component analysis separated the untreated endocrinopathies. The serum samples of dogs with untreated endocrinopathies showed various metabolic abnormalities with often contrasting results particularly in serum concentrations of fatty acids, and high- and low-density lipoproteins and their constituents, which were predominantly increased in hyperadrenocorticism and decreased in hypoadrenocorticism, while amino acid concentrations changed in various directions. Many observed serum metabolic abnormalities tended to normalize with medical treatment, but normalization was incomplete when compared to levels in apparently healthy dogs. Application of machine learning models based on the metabolomics data showed good classification, with misclassifications primarily observed in treated groups. Characterization of metabolic changes enhances our understanding of these endocrinopathies. Further assessment of the recognized incomplete reversal of metabolic alterations during medical treatment may improve disease management.