Free and Total Cortisol Levels as Predictors of Severity and Outcome in Community-acquired Pneumonia

Abstract

Cortisol levels are predictors of severity and outcome in CAP to a similar extent to the PSI, and are better than routinely measured laboratory parameters. In CAP, the prognostic accuracy of FC is not superior to TC. Clinical trial registered with www.controlled-trials.com (ISRCTN04176397).

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

“…Baseline total levels may also not contribute when inversely related to increases in cortisol upon ACTH [4,6]. Total cortisol increases upon ACTH had somewhat greater prognostic value than free cortisol increases in our patients, in partial agreement with other observations [16]. Otherwise, the role of etomidate in depressing ACTH-induced cortisol responses has been described before, and the frequency of low responses is also in line with the literature [1][2][3][4][5][6][7].…”

“…Together with the reported lowered binding capacity of cortisol for CBG in febrile sepsis [8,23], this may also explain why CBG rather than albumin affected free cortisol in sepsis and even less so than in non-sepsis. In any case, free cortisol was closely related to total cortisol levels, regardless of the underlying conditions, so that both free and total cortisol levels increased in relation to severity of illness, as reported before [4,6,16]. Nevertheless, total cortisol somewhat underestimated a higher free cortisol, as observed before [14,15,17], in sepsis as compared to non-sepsis.…”

“…Finally, increases in free cortisol upon ACTH depend less on low binding proteins than raw levels, so that increases in total cortisol suffice in assessing adrenal insufficiency, particularly in sepsis. CBG is the major cortisol binding-protein in blood, so that, as our data confirm, the free cortisol fraction is only about 25% of total cortisol even in the critically ill, and direct measurements are needed when trying to assess free from total cortisol levels [1,4,5,9,11,[14][15][16][17][18]. Cortisol binding to CBG is saturable (690 nmol/l) and characterized by a molar binding ratio at high affinity [18].…”

“…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]. The intra-and interassay coefficients of variation were less than 7 and 8%, respectively.…”

“…Foregoing studies can be criticized because of changes in binding proteins such as cortisol-binding globulin (CBG) and albumin, confounding estimation of biologically active free cortisol from total cortisol measurements and thereby assessment of adrenal function [1,4,5,[7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Indeed, low binding proteins may overestimate relative adrenal insufficiency assessed from (increases in) total cortisol.…”