Domestic cats share indoor environments with humans and are exposed to endocrine-disrupting chemicals (EDCs) from both household sources and cat-specific products capable of disrupting thyroid hormone signaling. The prevalence of feline hyperthyroidism (FHT) continues to rise, and while some EDCs have been implicated in its etiopathogenesis, the metabolic consequences of FHT are unknown. Here, we tested whether hyperthyroid cats exhibit altered systemic metabolomic signatures that are associated with phthalate and paraben urinary levels, compared with healthy controls. Thirty-five pet cats were enrolled (16 FHT, 19 controls). Serum samples were subjected to untargeted liquid chromatography mass spectrometry metabolomics and urine paraben and phthalates metabolites were quantified by liquid chromatography-tandem mass spectrometry. Forty-six serum metabolites and three urinary EDCs differed between groups (adjusted p < 0.05). Lipid metabolism pathways were enriched (16/74 significant; Fisher’s p = 0.02; False Discovery Rate-adjusted p = 0.16). Key serum differences included lower creatinine, linoleic acid, and 1-oleoyl-sn-glycerophosphoethanolamine in FHT. Urinary mono-isobutyl phthalate, ethylparaben, and propylparaben were higher in FHT (fold change 2.58, 3.30 and 2.07). Multivariable analyses separated groups; Weighted Sub-Network Analysis highlighted modules tied to tryptophan pathways, lipid homeostasis, and xenobiotic processing. Partial Least Squares captured 91% of response variance in two factors, with high-Variable Importance in Projection contributors including vitamin K1, 2-hydroxybenzothiazole, a sphingolipid long-chain base, and L-cysteine-glutathione disulfide. A Random Forest classifier achieved a 9.38% out-of-bag error and prioritized sphingoid bases and creatinine. Hyperthyroid cats had perturbed serum lipid-metabolite levels and higher urinary phthalate and paraben biomarker levels. These integrated data support an EDC-associated metabolomic signature in FHT and motivate longitudinal and mechanistic studies to clarify causality and inform prevention.
Ziv-Gal et al. (Mon,) studied this question.