Immunoreactive endogenous digoxin-like substances: plasma levels are dependent on the hypothalamic-pituitary-adrenal axis for release and on kidney function for elimination.

To identify factors that regulate the levels of immunoreactive digitalis-like substances (irEDLS) in body fluids, two studies were carried out. Plasma and urine levels of irEDLS were measured in uremic and normal subjects. Extracted material was fractionated (12 fractions) and assayed by digoxin radioimmunoassay. In four fractions, higher levels of irEDLS were found in uremic than in normal plasma. Urine from healthy subjects contained very high levels of irEDLS, but in urine collected from uremic patients irEDLS levels were similar to those in plasma. In another study, eight healthy subjects were given dexamethasone 1 mg orally and tetracosactide [an adrenocorticotropic hormone (ACTH) analogue] 0.25 mg i.v., on separate occasions. Dexamethasone suppressed the plasma and urine levels of cortisol and irEDLS. ACTH increased the levels of cortisol in plasma and urine, and of irEDLS in plasma. Taken together, these results support the hypothesis that irEDLS are of adrenal origin. However, decreased renal clearance, rather than increased production or release, may be the main cause of increased plasma levels of irEDLS in uremia.