Dissociation of plasma adrenocorticotropin and cortisol levels in critically ill patients: possible role of endothelin and atrial natriuretic hormone.

Abstract

The regulatory mechanisms of the hypothalamo-pituitary-adrenal system were studied in critically ill, intensive care unit patients. Serial measurements of immunoreactive ACTH-(1-39) (ACTHi), cortisol, endothelin-1 (ETi), and atrial natriuretic hormone (ANHi) were performed in blood samples of 18 patients with clinically defined sepsis, 12 critically ill patients after multiple trauma, and 15 hospitalized matched control subjects without acute illness for 8 consecutive days after admission. On admission, plasma levels of cortisol and ACTHi were significantly elevated in patients with sepsis (1.32 +/- 0.21 mumol/L and 130.0 +/- 38.2 pmol/L, mean +/- SD) and with multiple trauma (1.23 +/- 0.28 mumol/L and 123.7 +/- 41.3 pmol/L) compared to those in the control subjects (0.37 +/- 0.08 mumol/L and 15.6 +/- 5.8 pmol/L, respectively). The plasma cortisol levels of critically ill patients remained high (> 0.8 mumol/L) during the whole observation period. In contrast, plasma ACTHi levels decreased between days 3-5, reaching significantly lower levels on day 5 compared to those in the control group and remained below 5.0 pmol/L during the rest of the observation period. Plasma levels of ETi and ANHi were significantly elevated during the whole period in both patient groups (ETi, > 10 ng/L; ANHi, > 250 ng/L) compared to those in control subjects (< 5 and < 50 ng/L, respectively). The high plasma concentration of ETi observed in our patients may stimulate the steroid secretion of the adrenal cortex directly or potentiate the adrenal effect of ACTH. On the other hand, the increased concentration of ANHi found in critically ill patients together with the increased plasma cortisol level may explain the inhibition of ACTH secretion. Accordingly, we speculate that the high ET level exerts a positive drive on the adrenocortical level, that the high ANH level has an inhibitory effect on the hypothalamo-pituitary level, and that both mechanisms play a role in regulation of the hypothalamo-pituitary-adrenal axis during critical illness.

Adrenocortical function in patients with ruptured aneurysm of the abdominal aorta

“…Interestingly, in 30 patients, unstimulated plasma cortisol values were above 0.55 ~mol/1 while plasma ACTH was within the reference value (20-80ng/1). Although the pulsatile character of ACTH secretion limits the interpretation of a single ACTH measurement in the individual patient, the lack of correlation between ACTH and cortisol levels -a finding previously reported [12,13] -and reports of a hiphasic action response of the hypothalamic-pituitaryadrenocortical (HPA) axis in critically ill patients [14] and in patients undergoing abdominal surgery [15], showing high cortisol and ACTH levels in the first 2-4 clays with a subsequent sharp decrease in ACTH while cortisol levels remained high, provide further evidence that HPA activation during a critical illness is a complex process in which mechanisms other than simple feedback between ACTH and cortisol play a role. In this group of 54 patients with RAAA, one patient with an APACHE II score of 14 did not meet the criteria for normal adrenocortical function; the plasma cortisol value after ACTH stimulation was was 0.47 btmol/1.…”

The hypothalamic–pituitary–adrenal axis in critical illness

“…This biphasic response has been observed among adults with sepsis and adults with severe multiple trauma [41]. In addition to the components of the HPA axis, cytokines and other immune mediators play roles in the response to acute stress.…”

MECHANISMS IN ENDOCRINOLOGY: New concepts to further unravel adrenal insufficiency during critical illness

“…However, an observation which does not support such an HPA-axis activation during critical illness is the low plasma ACTH. Vermes et al (40) showed that plasma ACTH concentrations in patients suffering from severe trauma or sepsis were only transiently elevated and after a few days dropped below those observed in healthy control subjects in the face of high plasma cortisol. Furthermore, in a more heterogeneous long-stay ICU patient population, plasma ACTH concentrations were found to be suppressed from day 1 in ICU throughout the first week of critical illness, again in the presence of high plasma cortisol (41).…”

“…First, if a primary adrenal failure would be the reason for an insufficiently increased cortisol production and thus insufficiently increased plasma cortisol concentrations, one would expect a high plasma ACTH concentration, which has not been reported (40,41). Secondly, it was shown that the cortisol incremental cortisol response to an ACTH stimulation test in critically ill patients correlated positively with both cortisol production rate and cortisol plasma clearance (41) (Fig.…”