RF09 | PSAT88 Pro-opiomelanocortin (POMC), ACTH and Cortisol Responses to Pediatric Cardiac Surgery

INTRODUCTION: In critically ill adults, high plasma free cortisol in face of suppressed plasma ACTH coincides with high plasma pro-opiomelanocortin (POMC), the ACTH precursor (1). Further augmenting the systemic glucocorticoid availability with hydrocortisone treatment further lowered plasma ACTH, while plasma POMC remained unaffected (2). The dynamics of POMC in relation to ACTH and free cortisol prior to intensive care unit (ICU) admission are unknown, as well as the impact hereon of glucocorticoid treatment. Also, elevated plasma POMC concentrations have not yet been confirmed in pediatric ICU (PICU) patients. In pediatric cardiac surgery-induced critical illness, we hypothesized that plasma POMC is elevated and that plasma ACTH transiently rises per-operatively and becomes suppressed once free cortisol has risen on PICU day 1 and 2. In addition, we hypothesized that in patients receiving glucocorticoids per-operatively, plasma ACTH is further suppressed while plasma POMC is unaffected. METHODS: From 53 children aged 0-36 months, who underwent cardiac surgery and were admitted to the PICU, blood samples were taken prior to surgery (pre-operatively, available samples N=51), during surgery (per-operatively, N=47), on the following morning (PICU day 1, N=40) and the day hereafter (PICU day 2, N=24). Blood samples were also collected from 24 age- and gender-matched healthy children. To investigate the impact of synthetic glucocorticoid treatment on the endogenous plasma hormone concentrations, patients were categorized into steroid-naive (total N=38) and steroid-treated patients (total N=15). Plasma hormone concentrations were quantified with highly-specific ELISA (POMC), RIA (ACTH, cortisol, CBG) or colorimetric assays (albumin). Cross reactivity with synthetic glucocorticoids within the used cortisol RIA is minimal (<0.27% for methylprednisolone, <0.1% for dexamethasone). Free cortisol was estimated with the adapted Coolens’ formula. RESULTS: Plasma POMC was increased pre-operatively (p<0.0001) but no longer thereafter (p>0.05), irrespective of steroid treatment. Plasma ACTH in patients was never higher than in healthy children. While in steroid-naive patients, plasma ACTH became suppressed only by PICU day 1 (p<0.0001), steroid-treated patients had already suppressed plasma ACTH per-operatively (p≤0.0001). In steroid-naive patients, plasma free cortisol was increased from per-operatively onwards (p≤0.002), while in steroid-treated patients, plasma free cortisol (endogenous) concentrations always remained comparable to those of healthy children (p>0.05). CONCLUSION: Pre-operatively high plasma POMC, not followed by increased ACTH, suggests a centrally-activated HPA-axis already prior to surgery and an immature pituitary processing of POMC into ACTH. Systemic glucocorticoid availability is elevated from surgery onwards, likely driven by ACTH-independent mechanisms. Further increasing systemic glucocorticoid availability exogenously with glucocorticoid administration accelerates the suppression of plasma ACTH. The long-term impact of early glucocorticoid treatment in critically ill children remains to be investigated. REFERENCES: (1) Téblick A. et al. Critical Care 2021. (2) Téblick A. et al. Endocrinology 2022. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:42 p.m. - 1:47 p.m.