Background: A partial or complete steroid resistance, whose cause is not yet clarified, has been documented in many patients with long-standing Crohn's disease (CD). The primary aim of this study was to evaluate the number and affinity of serum protein steroid-binding sites in steroid-resistant patients with Crohn's disease. A secondary goal was to measure insulin sensitivity, an indirect index of steroid effectiveness, in these patients.
Methods: The study included 8 male steroid-resistant patients with active ileal CD and 6 healthy male volunteers. Corticosteroid binding globulin (CBG), binding capacity and affinity for cortisol were measured. The binding of cortisol to normal human serum and to serum of patients with CD was also determined. Whole body glucose uptake and oxidation were assessed by euglycemic hyperinsulinemic clamp and indirect calorimetry.
Results: Crohn's patients showed a significantly greater capacity of serum albumin for cortisol than controls (by about 40%, or about 0.15 moles per mole). Conversely, the binding of cortisol to CBG did not show significant differences between groups. Glucose uptake was higher in Crohn's patients than in normal controls (8.82 +/- 2.50 vs 7.01 +/- 2.24 mg/kgFFM/min; P = 0.036). Basal serum nonesterified fatty acid (NEFA) levels were lower in patients than in controls (459.64 +/- 69.95 vs 1026.48 +/- 112.58 mumol/L; P = 0.002).
Conclusions: The observed increase in albumin binding might limit the bioactivity of cortisol in patients with Crohn's disease and contribute to the decreased effectiveness and weaker side effects of glucocorticoid therapy in these patients. The increased number of cortisol binding sites on albumin from patients with CD might be correlated with the significant decrease in serum NEFA, which may compete with steroids for the same sites.