Liver Function in Relation to Possible Abnormalities of Steroid Metabolism in Rheumatoid Arthritis
Authors: L. M. H. Roy, F. W. Wigzell, R. Demers, R. J. G. Sinclair, J. J. R. Duthie, S. M. Atherden, G. F. Marrian
Journal: Annals of the Rheumatic Diseases (1955)

1950) claimed to have shown conclusively that in patients suffering from rheumatoid arthritis an abnormally high proportion of progesterone administered by the intramuscular route was excreted in the urine as pregnanediol.Further results pointing to the same conclusion were subsequently obtained by Sommer- ville (1950).These findings were thought to be of possible significance in connexion with the aetiology of rheumatoid arthritis, since the symptoms of that disease were known to be suppressed by cortisone, which is closely related chemically to progesterone and may be metabolized in the body in much the same way.As a preliminary to more extensive in- vestigations which were being planned, it was thought desirable in the first instance to extend the observations on progesterone metabolism in a further series of normal and rheumatoid arthritic subjects.Before the completion of this further series it was clear that, contrary to the findings of Sommerville and others (1950) and Sommerville (1950), there was no marked abnormality in the pregnanedibl excretion in the majority of rheumatoid arthritic subjects, but, since some of the latter showed pregnanediol recoveries outside the range which had been regarded as "normal" by Sommerville and others (1950), it was felt that further investigations would be advis- able.There is some evidence from studies on human subjects and experimental animals that severe liver dysfunction may be associated with an abnormally high urinary excretion of pregnanediol after the administration of progesterone (Paschkis, Can- tarrow, and Havens, 1951; Russell, 1952).Further- more, it has been claimed by some authors (Rawls, Weiss, and Collins, 1939; Hench, Bauer, Dawson, Hall, Holbrook, Key, and McEwan, 1941;Miller, 1935;Darby, 1953) that abnormalities in liver function occur not infrequently in rheumatoid arthritic subjects.Accordingly the possibility was considered that the apparent abnormalities in progesterone metabolism observed in some rheumatoid arthritic subjects might be confined to those with abnormalities in liver function.In view of this possibility, and of the conflicting results reported by various authors, it was decided to undertake a thorough investigation of liver function by a number of recognized tests in an unselected group of patients suffering from rheumatoid arthritis.This part of the study was specifically designed to investigate the possible association of impairment of liver function with abnormal progesterone metabolism.Only those cases showing significant abnormalities in liver function were to be submitted to tests of pro- gesterone metabolism.At the same time it was decided to extend the observations on progesterone metabolism in a further group of normal and rheu- matoid subjects.The two parts of the investigation were to a large extent carried out independently.The results of the work on liver function are presented in Part I of this communication and those on progesterone metabolism in Part II. I. LIVER FUNCTION IN RHEUMATOID ARTHRITISDuring the past 30 years many conflicting reports have appeared on liver function in relation to rheumatoid arthritis.The metabolism in the liver of protein and of carbohydrate has received most attention, but, although there is general agreement on the existence of abnormalities in protein meta- bolism, no such agreement can be found with respect 183 copyright.