Temperature-dependent cortisol distribution among the blood compartments in man

This study was conducted to investigate the effect of temperature on the amount of cortisol bound to the erythrocytes and the distribution of cortisol in whole blood at various temperatures. The amount of cortisol bound to the erythrocytes was determined in a way that did not disturb the equilibrium distribution of cortisol between plasma and erythrocytes. Total and free cortisol concentrations in plasma and the amount of cortisol bound to the erythrocytes were determined at 20, 30, 37, and 40 C in the blood of six healthy persons. The amount of cortisol bound to the erythrocytes showed a perfect linear relation with the free cortisol concentration and was independent from the temperature. The average ratio of the erythrocyte-associated and free cortisol was 2.38 +/- 0.06. Computer simulations of the distribution of cortisol among the blood compartments showed that the free and loosely bound fraction (albumin and erythrocytes) was highly temperature dependent: at 30 C, this fraction was 3-5 times lower than at 37 C. It was demonstrated by computer simulation that changes in the concentration of cortisol-binding globulin had an effect on the fractional distribution of cortisol among the blood components. These shifts in the cortisol distribution, between the erythrocyte and the plasma compartment, can also be the cause of apparently high or low free and total plasma cortisol concentrations. Differences up to 25% in the free cortisol concentration can be observed. We conclude that the erythrocyte-associated cortisol fraction is relatively undervalued but can serve as an important transport vehiculum and storage compartment for cortisol. This fraction can have a considerable effect on the total plasma and free cortisol concentration when strict temperature control during sample handling is not considered.