Increased free plasma corticosterone and adrenal hyperactivity associated with graft-versus-host disease

This study profiles adrenal function in 14-day-old neonatal and adult rats with graft-versus-host disease (GVHD). Measurements of adrenal function included total serum corticosterone, the relative percentage of free corticosterone (a measure of biologically active hormone), adrenal cholesterol content, adrenal weights, and adrenal histology. Diseased animals in both age groups displayed a shift from the protein-bound to the free corticosterone fraction, with, surprisingly, no change in total serum corticosterone titers. We discuss the possibility that such a shift toward the biologically active, free-hormone pool results in a physiologic hyperglucocorticoidism that might contribute to the progress of GVHD. Compared with littermate controls, diseased adults had enlarged adrenals. In neonates with GVHD, no adrenal hypertrophy was evident, yet decreased adrenal cholesterol content and associated depletion of adrenal lipid droplets--evidence of adrenal hyperactivity--were identified. The GVHD must be responsible for the observed alterations in adrenal function because treatment of affected animals with alloantiserum directed against donor cells halted the disease and elevated the cholesterol content toward control levels. The possible contribution of adrenal dysfunction to the pathogenesis of secondary manifestations of GVHD is discussed.