Metabolomic and inflammatory signatures in congenital hypothyroidism: a longitudinal analysis of levothyroxine response.

Authors

Marcela Vela-Amieva, Isabel Ibarra-González, Raúl Calzada León, María de la Luz Ruiz-Reyes, María Eugenia Constantini, Sara Guillén-López, Lizbeth López-Mejía, Michelle Citlalli Luna-Nequiz, Rosa Itzel Carrillo-Nieto, Cynthia Fernández-Lainez

Published in

Frontiers in endocrinology. Volume 17. Pages 1824072. Epub Jul 01, 2026.

Abstract

Congenital hypothyroidism (CH) requires early levothyroxine (LT4) replacement to prevent neurodevelopmental impairment. Treatment monitoring relies primarily on thyroid-stimulating hormone (TSH) and thyroxine (T4); however, these markers may not fully capture systemic metabolic changes during therapy. We aimed to explore metabolomic and inflammatory signatures associated with the biochemical response to LT4 treatment in pediatric patients with CH.
A prospective longitudinal study was conducted in 11 pediatric CH patients. Plasma samples were collected at diagnosis (Pre Tx) and after biochemical euthyroidism was achieved (Post Tx; mean follow-up 2.7 months). Metabolomic profiling was performed using tandem mass spectrometry. Inflammatory status was assessed by measuring plasma tumor necrosis factor-alpha (TNF-α) and interleukin 10 (IL-10). Nutritional status was also evaluated.
A group of nine metabolites discriminated between Pre Tx and Post Tx samples. The main metabolic changes involved sphingolipid metabolism, characterized by reduced ceramides (Cer) and hexosylceramides (HexCer), together with increased levels of specific sphingomyelins (SM). Circulating TNF-α and IL-10 concentrations were markedly elevated at diagnosis and remained elevated after treatment. Although both cytokines showed a decreasing trend following LT4 therapy, no statistically significant differences were observed between time points. Nutritional assessment showed a modest increase in length-for-age Z-score in the Post Tx group. Given the recognized roles of sphingolipids in cellular signaling and inflammatory regulation, this lipid changes may reflect broader metabolic adaptations during treatment.
LT4 therapy in CH pediatric patients was associated with changes in circulating sphingolipids, suggesting remodeling of sphingolipid metabolism after treatment initiation. Metabolomic profiling may provide complementary information on metabolic changes occurring during therapy and could contribute to a more detailed characterization of treatment response in CH.

PMID:
42460316
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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