Dynamic pituitary-adrenal interactions in the critically ill after cardiac surgery

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 characterise the secretory dynamics of the HPA axis in the critically ill after cardiac surgery.

DESIGN: Mathematical modelling of cohorts.

SETTING: Cardiac critical care unit.

PATIENTS/SUBJECTS: 20 male patients critically ill (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-minutes for 24-hours.

RESULTS: All critically ill patients had pulsatile ACTH and cortisol profiles. Critically ill patients had similar ACTH secretion (1036.4(737.6)pg/ml/24hrs) compared to the healthy volunteers (1502.3(1152.2)pg/ml/24hrs, p=0.2), but increased cortisol secretion (CI:14447.0(5709.3) v H:5915.5(1686.7)nmol/L/24hrs, p<0.0001). This increase in cortisol was due to non-pulsatile (CI:9253.4(3348.8) v H:960(589.0)nmol/L/24hrs, p<0.0001), rather than pulsatile cortisol secretion (CI:5193.1(3018.5) v H:4955.1(1753.6)nmol/L/24hrs, p=0.43). 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 critically ill. The reduced ACTH and increase in non-pulsatile cortisol secretion imply that the secretion of cortisol is driven by factors outside the HPA-axis in critical illness.