Pituitary-adrenocortical function was studied in patients with chronic renal failure (CRF) and compared with that in normal subjects. All CRF patients were on chronic hemodialysis. The mean morning plasma total and free (nonprotein bound) cortisol levels were higher in patients with CRF. Episodic secretion of cortisol was studied in plasma sampled every 20 min for 24 h. CRF patients demonstrated normal circadian rhythmicity, as evidence by times of peak secretory activity and number of peaks per 24 h. Mean 24-h plasma total cortixol levels were twice the normal levels in CRF patients. Nine of 10 patients with CRF did not suppress plasma total cortisol levels with 1 mg dexamethasone. Four of 10 patients with CRF suppressed with 2 mg dexamethasone orally for 2 days, 5 patients suppressed after 8 mg dexamethasone administration, and 1 patient with CRF resisted suppression. Hemodialysis did not alter mean 24-h cortisol levels or numbers of secretory episodes but produced a shift of secretory activity into the dialysis time period. These studies show alterations in cortisol dynamics in which increased plasma cortisol levels and dexamethasone resistance coexist with normal circadian rhythmicity.
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.
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