Variations have been shown to occur in the quantitative urinary excretion pattern of the metabolites of cortisol in a variety of traumatic events such as surgery, bone fracture and burns (1). The compounds evaluated were THF, allo-THF and THE,' and it was demonstrated that the relative proportion of THF: THE excreted during and after a "traumatic event" was markedly increased. In addition almost complete absence of allo-THF was observed in a chronically ill individual and it reappeared upon convalescence. The rate of secretion of cortisol was one factor involved in producing the increase in urinary THF: THE, since following the administration of adrenocorticotropin (ACTH) to normal individuals the relative proportion of urinary THF as compared with THE was observed to rise (1)(2)(3)(4)(5) factors other than the rate of adrenal secretion were involved in altering the rates of excretion of the numerous metabolites of cortisol. It became clear that knowledge concerning the pathways of metabolism, the pool sizes of the metabolites and the relative rates of formation of the individual metabolites from cortisol would prove valuable in interpreting the urinary excretion patterns of these compounds.2 Consequently these studies were undertaken to determine the extent of the reaction THF = THE in volunteer subjects with and without the administration of ACTH; the pathways for the formation of THF, allo-THF, THE and cortolone from cortisol; the miscible pool size of THF, allo-THF, THE and cortolone; and the possibility of determining the overall rates of formation of THF, allo-THF and THE. This work was performed in volunteer subjects with cortisol-4-C14 as a tracer.
METHODSGeneral plan. Tracer doses of cortisol4-C' (1 puc., about 250 ,ug.) were administered intravenously to normal volunteer subjects and urine samples were collected every 15 minutes. The specific activity of cortisol and its metabolites was determined as a function of time, and pool sizes and pathways were determined by isotope dilution procedures after the intravenous administration of small amounts of unlabeled cortisol metabolites. The rates of formation of these metabolites were computed in several instances using the criteria described by Zilversmit, Entenman and Fishler (6