Dynamic Pituitary–Adrenal Interactions in the Critically Ill after Cardiac Surgery

Abstract Context Patients with critical illness are thought to be at risk of adrenal insufficiency. There are no models of dynamic hypothalamic–pituitary–adrenal (HPA) axis function in this group of patients and thus current methods of diagnosis are based on aggregated, static models. Objective To characterize the secretory dynamics of the HPA axis in the critically ill (CI) after cardiac surgery. Design Mathematical modeling of cohorts. Setting Cardiac critical care unit. Patients 20 male patients CI at least 48 hours after cardiac surgery and 19 healthy (H) male volunteers. Interventions None. Main Outcome Measures Measures of hormone secretory dynamics were generated from serum adrenocorticotrophic hormone (ACTH) sampled every hour and total cortisol every 10 min for 24 h. Results All CI patients had pulsatile ACTH and cortisol profiles. CI patients had similar ACTH secretion (1036.4 [737.6] pg/mL/24 h) compared to the H volunteers (1502.3 [1152.2] pg/mL/24 h; P = .20), but increased cortisol secretion (CI: 14 447.0 [5709.3] vs H: 5915.5 [1686.7)] nmol/L/24 h; P < .0001). This increase in cortisol was due to nonpulsatile (CI: 9253.4 [3348.8] vs H: 960 [589.0] nmol/L/24 h, P < .0001), rather than pulsatile cortisol secretion (CI: 5193.1 [3018.5] vs H: 4955.1 [1753.6] nmol/L/24 h; P = .43). Seven (35%) of the 20 CI patients had cortisol pulse nadirs below the current international guideline threshold for critical illness-related corticosteroid insufficiency, but an overall secretion that would not be considered deficient. Conclusions This study supports the premise that current tests of HPA axis function are unhelpful in the diagnosis of adrenal insufficiency in the CI. The reduced ACTH and increase in nonpulsatile cortisol secretion imply that the secretion of cortisol is driven by factors outside the HPA axis in critical illness.