Corticosteroid Metabolism and Rheumatoid Arthritis

It is generally held that cortisol (hydrocortisone) is metabolized in the liver (Peterson, Wyngaarden, Guerra, Brodie and Bunim, 1955; Bush, 1962). If this is the case the effective concentration of cortisol in all other tissues will be determined by its concentration in non-protein-bound (n-p-b) form in plasma. If, on the other hand, cortisol is metabolized by enzymes in extra-hepatic tissue cells, it is these enzymes that will be the final determinant of the effective concentration within such cells. It will be necessary therefore to study the activity of these enzymes in any diseased tissue (e.g. connective tissue) that is sensitive to small changes in the concentration of plasma cortisol. In this paper evidence will be presented for the existence of extensive extra-hepatic metabolism of cortisol and detail will be given of attempts made to detect abnormal extra-hepatic metabolism of cortisol and prednisolone in rheumatoid arthritic patients.