Aim of the work: The time courses of ACTH, (free) cortisol and cortisol metabolites beyond the first week of critical illness and upon recovery have not been documented. We studied adrenocortical function over time in relation to critical illness duration and presence of sepsis/septic shock, to initiation of glucocorticoid treatment, and to recovery/death.
Methods: Patients still in ICU on day 7 (N=392) and 20 matched healthy subjects were included. Morning blood and 24h-urine were collected daily and cosyntropin tests (Synacthen®, 250 μg) performed weekly, repeated 7 days after ICU-discharge.
Main results: In patients who remained free of glucocorticoid treatment until ICU-day 28 (N=347), plasma ACTH remained low/normal, whereas free cortisol remained high (P≤0.002) explained by reduced binding proteins (P≤0.02) and suppressed cortisol breakdown (P≤0.001). Beyond ICU-day 28 (N=64 long-stayers), plasma ACTH and (free)cortisol became comparable to healthy subjects. Long-stay-patients always showed low incremental total (P≤0.001), but normal incremental free, cortisol responses to weekly cosyntropin-tests, explained by low binding proteins whereby increased cortisol distribution volume. Sepsis/septic shock patients were not different from others, patients subsequently receiving glucocorticoids (N=45) were not different from those who did not, and non-survivors were distinguishable from survivors only by higher (free) cortisol. One week after ICU-discharge, plasma ACTH and (free)cortisol increased to supra-normal levels (P≤0.006).
Conclusions: Low plasma binding proteins and suppressed cortisol breakdown in prolonged critical illness confound interpretation of cosyntropin-test results. The absence of elevated ACTH and free cortisol beyond ICU-day 28, followed by a clear rise after ICU-discharge, suggests central adrenocortical suppression that could predispose long-stay ICU patients to adrenal insufficiency.
19 - 20 Oct 2018
Belgian Endocrine Society