Effect of Liver Disease Upon Steroid Circadian Rhythms in Man

Abstract

Summary Steroid circadian variations were studied in 11 patients with biopsy-proven liver disease and compared with observations in eight normal control subjects. Plasma and urinary unconjugated, plasma conjugated, and urinary total 17-hydroxycorticosteroid (17-OHCS) levels were determined in six consecutive 4-hr periods, the plasma levels being measured at the midpoint of each urine collection. In the patients with liver disease, plasma unconjugated as well as conjugated 17-OHCS levels were within the normal range in the morning. Plasma unconjugated 17-OHCS demonstrated a circadian variation within the broad limits of normal in four of eight patients with liver disease studied. In the remaining four, peak levels were maintained longer than normal or else the variation was markedly reduced. Plasma conjugated 17-OHCS showed a slower than normal rise and broader peak resulting in inversion of the normal diurnal rhythm in six of the eight patients investigated. The urinary findings reflected the plasma changes. The 24-hr excretion of free 17-OHCS in the urine was significantly greater than in the normal subjects, whereas total 17-OHCS excretion in contrast was reduced. The observations are in keeping with earlier studies of the effect of liver disease on the disposition of infused cortisol and the response to adrenocorticotropin (ACTH). The findings support the concept of hepatic regulation of pituitary ACTH secretion by the feedback mechanism in that progressive impairment in hepatic degradation of cortisol may lead to a lessened diurnal variation of the unconjugated 17-OHCS, pituitary suppression, and, in turn, reduced adrenocortical cortisol production.