Control mechanisms of adrenocorticotrophic hormone (ACTH) and cortisol (CORT) secretion and metabolism during acute systemic inflammation (e.g. major surgery) have never been clearly elucidated. We sampled blood every 10 minutes for 12 h during and after coronary artery bypass grafting (CABG) in 10 patients to create profiles of ACTH, CORT and inflammatory mediators and compared these to healthy controls. Patients ACTH and CORT responses were classified into one of three groups:
Single-pulse: single peak in 12 h, strong peak dissociation (mlag=77min) and unstable peak synchrony,
Two-pulse: prolonged periodicity (Tu=5-6 h), peak association (mla=13 min), stable peak synchrony, or
Multiple-pulses (normal periodicity (Tu=2 h), peak dissociation (mlag=106 min) and partial peak synchrony.
We used an ACTH-dependent, two-compartment mathematical model of CORT activity to investigate the physiological changes underlying these patterns. The model has six parameters representing the fast and slow adrenal maximum secretory capacity, fast and slow CORT turnover rates, the adrenal sensitivity to ACTH stimulation, and a Hill coefficient indicating the steepness of the non-linear adrenal response to ACTH. By fitting the model parameters to control and patient groups, we identified the physiological processes regulating CORT activity that are likely disrupted by surgery. Patients in the single-pulse group had a greater slow adrenal secretory capacity and very prolonged slow turnover rate for CORT compared to controls. Those in the two-pulse group had similar adrenal secretory capacity and a slightly increased slow turnover rate compared to controls. Those in the multiple-pulse group had a slightly increased slow adrenal secretory capacity and slightly increased slow turnover rate. This study shows that patients ACTH and CORT responses to CABG fit one of three phenotypes which exist due to differential changes in the underlying secretion, distribution and metabolism of cortisol. A suitably powered study is now required to establish whether these affect clinical outcome.
08 Nov 2021 - 10 Nov 2021