The dynamic adrenal response of children to cardiac surgery and cardiac catheterisation

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ID: 313718
2026
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Abstract
Abstract Context The hypothalamic-pituitary-adrenal (HPA) axis is the key homeostatic system regulating the response to surgical stress. Imbalances in HPA axis hormones increase morbidity and mortality in children after cardiac surgery. Despite this, the physiology of the HPA axis in children undergoing cardiac surgery is poorly understood, leading to controversies in clinical practice. Objective To characterise dynamic HPA axis responses in children undergoing cardiac surgery and to determine age- and procedure-related differences in cortisol and cortisone physiology. Methods We recruited children (0-18 years) undergoing cardiac surgery with cardiopulmonary bypass or cardiac catheterisation. Tissue-free cortisol and cortisone were sampled every 20 minutes for up to 24 hours via microdialysis, alongside serum adrenocorticotropic hormone (ACTH), cortisol, cortisol-binding globulin (CBG), and inflammatory markers. We developed dynamic markers to quantify age- and procedure-dependent differences in hormonal responses and built a mathematical model to explain them. Results Neonates undergoing surgery showed higher free cortisol and cortisone AUC and peak concentrations than catheterisation patients. Neonates had higher peaks of cortisol and cortisone than older children undergoing surgery. The much higher tissue cortisone levels observed in neonates can be explained by enzymatic interconversion between cortisol and cortisone, likely due to persistent foetal high 11-βHSD2 activity and reduced 11-βHSD1 activity. Low post-operative blood cortisol and CBG values in neonates resulted in high free cortisol peaks in interstitial fluid during and after surgery. Conclusion Neonates differ physiologically, with higher free cortisol levels that more readily diffuse into interstitial tissues, with implications for perioperative management.
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Authors Daniel Fudulu, Isabella Marinelli, Daniel Galvis, Eder Zavala, Terrie Walker-Smith, Jonathan Evans, Fanoula Papadopoulou, Thomas Upton, Aravind Ramesh, Filippo Rapetto, Yvonne Kershaw, Jan Fox, Angela Aramburo, Șerban Stoica, Massimo Caputo, A PARRY, Duncan Macrae, Guido Michielon, J. Andreas Hoschtitzky, Karen Sheehan, Martijn van Faassen, Ido Kema, Gianni Davide Angelini, Stafford Lightman, Ben Gibbison
Journal the journal of clinical endocrinology & metabolism
Year 2026
DOI
10.1210/clinem/dgag206
URL
https://doi.org/10.1210/clinem/dgag206
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