Pituitary-Adrenocortical Function in Chronic Renal Failure: Blunted Suppression and Early Escape of Plasma Cortisol Levels after Intravenous Dexamethasone*

Abstract

The response to iv dexamehasone was studied in patients with chronic renal failure in whom resistance to suppression of plasma cortisol levels after oral steroid had been reported previously. One milligram of dexamethasone was given iv at 2300 h, and plasma cortisol levels were measured every 20 min between 0500-1000h in patients with renal failure, normal controls, and patients with pituitary-dependent Cushing's syndrome. Normal subjects showed a decrease in mean plasma cortisol levels to less than 3 micrograms/dl; patients with Cushing's syndrome showed no suppression of cortisol secretory activity during the sampling period. In renal failure patients, morning cortisol levels fell to values lower than those achieved when the 1-mg dose was given orally or when the steroid was not given, but did not suppress to the levels seen in normals. Early resumption of cortisol secretion occurred in four of five renal failure patients during the 6-11 h after dexamethasone administration. These studies show that iv dexamethasone is more effective than the oral steroid in suppressing pituitary-adrenocortical activity in renal failure patients. However, the incomplete suppression and early resumption of cortisol secretion which are present in chronic renal failure patients even after iv dexamethasone support the suggestion that they have disordered feedback control of the hypothalamic-pituitary-adrenocortical axis.

Paper Chromatography prior to Cortisol RIA Allows for Accurate Use of the Dexamethasone Suppression Test in Chronic Renal Failure

“…Others [5]have suggested that intravenous dexamethasone may be more effective than oral dexamethasone in patients on hemodialysis. Some investigators [6, 7, 8]have suggested that a higher oral dose of dexamethasone be used for testing in renal failure patients.…”

“…Dexamethasone suppression tests have been reported to be unchanged by some [3]and blunted by others [4, 5, 6, 7, 8]in patients on chronic hemodialysis. This lack of suppressibility has been attributed to various factors.…”

“…This lack of suppressibility has been attributed to various factors. Diminished oral absorption of dexamethasone has been proposed [6]; however, lack of suppressibility can be seen even after intravenous administration of the drug [5]. Accelerated metabolism of dexamethasone in chronic renal failure has been advanced as a possible explanation [9]; however, although levels of dexamethasone after intravenous administration have been reported to be normal, cortisol levels were still incompletely suppressed [5].…”

“…Diminished oral absorption of dexamethasone has been proposed [6]; however, lack of suppressibility can be seen even after intravenous administration of the drug [5]. Accelerated metabolism of dexamethasone in chronic renal failure has been advanced as a possible explanation [9]; however, although levels of dexamethasone after intravenous administration have been reported to be normal, cortisol levels were still incompletely suppressed [5]. Increased hepatic metabolism of dexamethasone with abnormal dexamethasone suppression testing has also been documented in patients on chronic anticonvulsant therapy [10, 11].…”

Hormonal Changes in Hemodialysis

“…Despite reduced excretion via the kidneys, baseline levels as well as diurnal vari ation and homeostatic regulation of cortisol appear near normal in most RDT patients [6,[95][96][97][98]. Measurements of adrenocortico tropic hormone are unreliable in uremia be cause of the accumulation of retained cross reacting substances.…”