ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)
Metabolomic profiling of premature adrenarche reveals a unique acylcarnitine-dominated signature
Jani Liimatta 1,2 , Therina du Toit 3,4 , Iman Zarei 5 , Retu Haikonen 5 , Tuomas Selander 6 , Marko Lehtonen 7 , Seppo Auriola 7 , Jean-Marc Nuoffer 3,4,8 , Anders Juul 9,10,11 , Timo Lakka 12,13,14 , Kati Hanhineva 5,15 , Christa Flück 3,4 & Jarmo Jääskeläinen 1,2
1Kuopio University Hospital, Department of Pediatrics, Kuopio, Finland; 2University of Eastern Finland, Institute of Clinical Medicine, Kuopio, Finland; 3University of Bern, Department of BioMedical Research, Bern, Switzerland; 4Bern University Hospital, Department of Pediatric Endocrinology, Diabetology, and Metabolism, Bern, Switzerland; 5University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, Finland; 6Kuopio University Hospital, Science Service Center, Kuopio, Finland; 7University of Eastern Finland, School of Pharmacy, Kuopio, Finland; 8Bern University Hospital, University Institute for Clinical Chemistry, Bern, Switzerland; 9Copenhagen University Hospital, Department of Growth and Reproduction, Copenhagen, Denmark; 10University of Copenhagen, International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark; 11University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark; 12University of Eastern Finland, Institute of Biomedicine, Kuopio, Finland; 13Kuopio University Hospital, Department of Clinical Physiology and Nuclear Medicine, Kuopio, Finland; 14Kuopio Research Institute of Exercise Medicine, Foundation for Research in Health Exercise and Nutrition, Kuopio, Finland; 15University of Turku, Food Sciences Unit, Department of Life Technologies, Turku, Finland
JOINT646
The mechanisms and regulatory factors underlying adrenarche, the development of the zona reticularis in the adrenal cortex, remain largely unknown. Children with premature adrenarche (PA) are typically taller and have a higher body fat percentage compared to peers with normally timed adrenarche. Notably, their growth acceleration and rapid weight gain can often be traced back to infancy, suggesting the possibility of early metabolic programming as a contributing factor. To explore this, we compared 16 girls with PA and 27 control girls, at the mean ages of 7 and 9 years, in a longitudinal study using a liquid chromatography mass spectrometry (LC–MS)-based untargeted metabolomics approach. PA was defined by at least one clinical sign of androgen action, accompanied by a serum DHEAS concentration exceeding 1 μmol/l, with other causes of androgenic signs ruled out. Both groups were comparable regarding background characteristics, including standardized body size at birth and diagnosis (length/height and BMI), basic biochemical parameters (glucose, insulin, and lipids), and dietary nutrient intake. Metabolites were analyzed from serum samples using LC–MS. Metabolomics data from PA girls at age 7 was compared to control girls at age 7 (‘age-matched’ comparison) and in addition also at age 9, when the control group exhibited adrenarchal signs (‘event-matched’ comparison), using linear mixed-effects models. In the age-matched comparison, 93 metabolite features differed significantly between the groups, with 74 being higher and 19 lower in PA girls. In the event-matched comparison, 128 metabolite features differed significantly between the groups, with 95 being higher and 33 lower in PA girls. Notably, 23 metabolites were identified in both comparisons, including 22 being consistently higher and 1 lower in PA girls. Among the 22 metabolites that were higher in PA girls, acylcarnitine metabolites were predominant, along with several fatty acid and steroid metabolites. The sole metabolite that was lower in the PA girls was a sulfate conjugate of the bacterial metabolite p-cresol. These findings suggest a potential involvement of fatty acid beta-oxidation in mitochondria and/or peroxisomes, and gut microbiome in the development of PA.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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