Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Cortisol metabolism in chronic kidney disease

Biff F Palmer, MD
William L Henrich, MD, MACP
Section Editor
Jeffrey S Berns, MD
Deputy Editor
Alice M Sheridan, MD


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 [1]. 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 [2]. Cortisol binding to corticosteroid-binding globulin remains normal, while binding to albumin is decreased [3].


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) [9]. 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 [12].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Mar 07, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Bacon GE, Kenny FM, Murdaugh HV, Richards C. Prolonged serum half-life of cortisol in renal failure. Johns Hopkins Med J 1973; 132:127.
  2. Nolan GE, Smith JB, Chavre VJ, Jubiz W. Spurious overestimation of plasma cortisol in patients with chronic renal failure. J Clin Endocrinol Metab 1981; 52:1242.
  3. Rosman PM, Benn R, Kay M, Wallace EZ. Cortisol binding in uremic plasma. II. Decreased cortisol binding to albumin. Nephron 1984; 37:229.
  4. Barbour GL, Sevier BR. Letter: Adrenal responsiveness in chronic hemodialysis. N Engl J Med 1974; 290:1258.
  5. McDonald WJ, Golper TA, Mass RD, et al. Adrenocorticotropin-cortisol axis abnormalities in hemodialysis patients. J Clin Endocrinol Metab 1979; 48:92.
  6. Siamopoulos KC, Dardamanis M, Kyriaki D, et al. Pituitary adrenal responsiveness to corticotropin-releasing hormone in chronic uremic patients. Perit Dial Int 1990; 10:153.
  7. Siamopoulos KC, Eleftheriades EG, Pappas M, et al. Ovine corticotropin-releasing hormone stimulation test in patients with chronic renal failure: pharmacokinetic properties, and plasma adrenocorticotropic hormone and serum cortisol responses. Horm Res 1988; 30:17.
  8. Watschinger B, Watzinger U, Templ H, et al. Effect of recombinant human erythropoietin on anterior pituitary function in patients on chronic hemodialysis. Horm Res 1991; 36:22.
  9. Ramirez G. Abnormalities in the hypothalamic-hypophyseal axes in patients with chronic renal failure. Semin Dial 1994; 7:138.
  10. Ramirez G, Gomez-Sanchez C, Meikle WA, Jubiz W. Evaluation of the hypothalamic hypophyseal adrenal axis in patients receiving long-term hemodialysis. Arch Intern Med 1982; 142:1448.
  11. Luger A, Lang I, Kovarik J, et al. Abnormalities in the hypothalamic-pituitary-adrenocortical axis in patients with chronic renal failure. Am J Kidney Dis 1987; 9:51.
  12. Hashimoto K, Nishioka T, Numata Y, et al. Plasma levels of corticotropin-releasing hormone in hypothalamic-pituitary-adrenal disorders and chronic renal failure. Acta Endocrinol (Copenh) 1993; 128:503.
  13. Rosman PM, Farag A, Peckham R, et al. Pituitary-adrenocortical function in chronic renal failure: blunted suppression and early escape of plasma cortisol levels after intravenous dexamethasone. J Clin Endocrinol Metab 1982; 54:528.
  14. Himmelfarb J, Holbrook D, McMonagle E, et al. Kt/V, nutritional parameters, serum cortisol, and insulin growth factor-1 levels and patient outcome in hemodialysis. Am J Kidney Dis 1994; 24:473.
  15. Jusko WJ, Milad MA, Ludwig EA, et al. Methylprednisolone pharmacokinetics and pharmacodynamics in chronic renal failure. Clin Nephrol 1995; 43 Suppl 1:S16.