Cortisol metabolism in chronic kidney disease
- Biff F Palmer, MD
Biff F Palmer, MD
- Professor of Internal Medicine
- University of Texas Southwestern Medical Center
- William L Henrich, MD, MACP
William L Henrich, MD, MACP
- Professor of Medicine
- President of the Health Science Center
- University of Texas Health Science Center School of Medicine
Assessment of the hypothalamic-pituitary-adrenocortical axis in patients with chronic kidney disease (CKD) has produced considerable controversy. As a consequence, the diagnosis of abnormal glucocorticoid metabolism can be challenging in this patient population.
The kidney normally contributes to the excretion of cortisol and its water-soluble metabolites. As a result, the serum half-life of cortisol becomes prolonged in advanced renal failure . Both normal and elevated levels of serum cortisol have been reported in this setting [2,3]. Methodological problems may in part account for the conflicting results. As an example, compounds (including metabolites of cortisol) accumulate in renal disease that can interfere with the accurate measurement of cortisol by several commercially available assays . Cortisol binding to corticosteroid-binding globulin remains normal, while binding to albumin is decreased .
TESTS OF ADRENAL AND PITUITARY FUNCTION
Adrenocorticotropic hormone, corticotropin-releasing hormone, and metyrapone stimulation tests — Tests designed to assess the secretory capacity of the adrenal gland are typically normal. Thus, the diurnal variation in cortisol release is well preserved, and circulating cortisol levels increase appropriately after an infusion of adrenocorticotropic hormone (ACTH) [4,5]. Cortisol levels also increase after the administration of corticotropin-releasing hormone (CRH); the expected rise in ACTH secretion is blunted in this setting, a response similar to that observed with chronic stress [6,7]. For reasons that are unclear, the ACTH response to CRH is improved by recombinant human erythropoietin [8,9].
Stimulation of ACTH and cortisol secretion following insulin-induced hypoglycemia or the infusion of CRH is impaired [10,11]. ACTH and 11-deoxycortisol responses are also blunted following the standard metyrapone test dose (30 mg/kg) . This defect may be due to adrenal resistance to the blocking action of metyrapone in renal failure since the response can be normalized by the administration of higher doses.
Interpretation of these abnormalities may be complicated by the effect of hemodialysis on the plasma concentrations of CRH, ACTH, and cortisol. CRH levels fall during hemodialysis due to clearance across the dialysis membrane; despite this change, ACTH and cortisol levels increase in most patients .
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