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59 NUMERICAL SOLUTION FOR CORTISOL EQUILIBRIUM AND MAXIMAL CORTISOL SECRETION RATES IN HUMAN SEPTIC SHOCK AND HEALTHY CONTROL SUBJECTS.
  1. H. K. Pai1,
  2. C. R. Qualls1,
  3. F. K. Urban III1,
  4. J. T. Ho1,
  5. D. J. Torpy1,
  6. J. G. Lewis1,
  7. F. I. Dorin1
  1. 1University of New Mexico, Albuquerque, NM.

Abstract

Septic shock (SS) is associated with an increase in total and free cortisol along with a disproportionate increase in percent free cortisol, due in part to decreased serum concentrations of cortisol-binding globulin (CBG) and albumin. Relative adrenal insufficiency (RAI) is often seen in septic shock and is biochemically defined by a cortisol increment < 9 μg/dL following a cosyntropin-stimulation test.

Objective Keenan et al proposed a set of three differential equations describing a dynamic model for free cortisol secretion and clearance rates, which incorporates the reactions of free cortisol with CBG and albumin, under non-steady-state conditions. We sought to assess maximal cortisol secretion rates in SS and in control subjects using numerical techniques to solve for cortisol equilibrium in the serum compartment and for cortisol secretion and clearance rates.

Methods Plasma total and free cortisol, serum CBG, and albumin were measured in subjects with SS (n = 45), subjects with sepsis (S, n = 19), and in healthy controls (HC, n = 10) at 0, 30, and 60 minutes after 250 μg cosyntropin. Numerical solution for cortisol secretion rates used group-specific KA determined by least squares solution and assumed a uniform, maximal cortisol secretion rate to provide a least squares solution for secretion and clearance to fit observed data points.

Results The group-specific KA was significantly higher in SS versus S and HC (148, 99, and 78 μM, p < .001). The increase in KA in the setting of SS was reversible following recovery from illness (p = .04). Maximal cortisol secretion rates were higher in SS, including subjects meeting criteria for RAI, when compared with either S or HC (p = .02).

Conclusions SS and RAI are associated with a reversible increase in KA, contributing to an increase in percent free cortisol. Maximal cortisol secretion rates are elevated in SS, including RAI subjects. The distribution of the normal range of maximal secretion rates (CV = 48%) suggests that application of numerical solution to non-steady-state conditions, such as the cosyntropin stimulation test, may be useful in distinguishing absolute and relative adrenal insufficiency.

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