Investigating changes in serum metabolome and urinary endocrine disrupting chemicals in cats with hyperthyroidism

TL;DR

This study finds that hyperthyroid cats have altered metabolites and higher levels of certain chemicals in their urine compared to healthy cats.

Contribution

The study identifies a novel metabolomic signature and links it to endocrine-disrupting chemicals in cats with hyperthyroidism.

Findings

Hyperthyroid cats had higher urinary levels of phthalates and parabens compared to controls.

Lipid metabolism pathways were enriched in hyperthyroid cats, with altered levels of specific metabolites.

Sphingolipid bases and creatinine were highlighted as potential predictors of thyroid status.

Abstract

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.

The online version contains supplementary material available at 10.1007/s11259-026-11169-5.

Hyperthyroid cats have higher urinary levels of phthalate and parabensHyperthyroid cats have pathway-specific alterations in fatty acid metabolismHyperthyroid cats have pathway-specific alterations in steroid hormones and amino acidsHyperthyroidism is linked to lipid imbalance, tryptophan and xenobiotic metabolismSphingolipid bases are suggested as potential predictors of thyroid status

Hyperthyroid cats have higher urinary levels of phthalate and parabens

Hyperthyroid cats have pathway-specific alterations in fatty acid metabolism

Hyperthyroid cats have pathway-specific alterations in steroid hormones and amino acids

Hyperthyroidism is linked to lipid imbalance, tryptophan and xenobiotic metabolism

Sphingolipid bases are suggested as potential predictors of thyroid status

The online version contains supplementary material available at 10.1007/s11259-026-11169-5.

Figures