Relative adrenal insufficiency as a predictor of disease severity, mortality, and beneficial effects of corticosteroid treatment in septic shock

Jong, Margriet F C de; Beishuizen, Albertus; Spijkstra, Jan Jaap; Groeneveld, A. B. J.

doi:10.1097/01.ccm.0000275387.51629.ed

Cited by 70 publications

(80 citation statements)

References 37 publications

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“…We found a lower cutoff (\100 nmol/l) for ACTHinduced increases to be associated with mortality and predicted a survival benefit of corticosteroid treatment in septic shock [6].…”

Section: Introductionmentioning

confidence: 76%

“…CBG and albumin apparently often change in dissimilar directions in sepsis as compared to non-sepsis, as suggested before [18]. Hence, the cortisol/ albumin ratios used to adjust for protein binding are probably invalid in this condition [6]. Moreover, the affinity of cortisol may be lowered in sepsis when albumin molecules are damaged [24].…”

Section: Discussionmentioning

confidence: 97%

“…The peak (at 30 or 60 min) minus baseline cortisol level was taken to calculate increases upon ACTH. A subnormal response to ACTH in critical illness was defined by a total cortisol increase \250 nmol/l or increase\100 nmol/l, as reported by others and ourselves [5,6]. Serum free cortisol levels were measured by equilibrium dialysis of undiluted serum samples followed by radioimmunoassay (Orion Diagnostica, Espoo, Finland; \6% cross reactivity with cortisone) [4,13,16,17,25,26].…”

Section: Patient Population and Acth Testmentioning

confidence: 99%

“…Relatively insufficient adrenal secretion of cortisol for the severity of illness, in the course of critical illness-related corticosteroid insufficiency (CIRCI), commonly occurs in the critically ill. This may warrant treatment by corticosteroids to survive septic shock, although this is hotly debated [2][3][4][5][6][7]. Adrenal function is mostly assessed by total cortisol measurements prior to and after injection of adrenocorticotropic hormone (ACTH).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, CIRCI may be more frequent in sepsis than in non-sepsis patients, and sometimes only calculated free cortisol was evaluated, thereby assuming normal albumin levels, while both CBG and albumin may be lowered [1-3, 5, 6, 8, 18, 22, 23]. We previously used (increases in) cortisol/albumin ratios to adjust for protein binding in critical illness, but these ratios were not validated, even though CBG and albumin levels commonly change in the same direction, and hypoalbuminemia has been suggested to increase the free cortisol fraction [4,6,18]. Other authors, however, suggest that CBG and albumin and their cortisol binding are differently regulated in sepsis as compared to non-sepsis [8,18,23,24].…”

Section: Introductionmentioning

confidence: 99%

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Assessing adrenal insufficiency of corticosteroid secretion using free versus total cortisol levels in critical illness

et al. 2011

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Purpose: To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illnessrelated corticosteroid insufficiency. Methods: A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 lg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed. Results: Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (r = 0.77-0.79, P \ 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower for sepsis vs. non-sepsis). Conclusions: Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis.

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“…We found a lower cutoff (\100 nmol/l) for ACTHinduced increases to be associated with mortality and predicted a survival benefit of corticosteroid treatment in septic shock [6].…”

Section: Introductionmentioning

confidence: 76%