Correspondence
Corticosteroid Insufficiency in Acutely Ill Patients
N Engl J Med 2003; 348:2157-2159May 22, 2003
- Article
To the Editor:
The review article by Cooper and Stewart on corticosteroid insufficiency in acutely ill patients (Feb. 20 issue)1 makes recommendations concerning the diagnosis and treatment of adrenal insufficiency in patients with septic shock. Although base-line cortisol and corticotropin testing may help to identify patients with an increased risk of death,2 it is still unclear how to define adrenal insufficiency.2,3 Various base-line cortisol levels, changes in cortisol levels, or both have been used,3 and none can as yet identify the subgroups of patients who have adrenal insufficiency and who benefit from the use of corticosteroids.3,4
The use of hydrocortisone has not been proved to be effective and safe for all patients with septic shock. Previous studies were small or evaluated only patients who had had systolic blood pressures below 90 mm Hg for more than one hour.4,5 CORTICUS, an ongoing European prospective, double-blind, multicenter study of hydrocortisone in patients with septic shock, should help to answer these important questions. In the meantime, the diagnosis of adrenal insufficiency in such patients remains controversial, and there continues to be clinical equipoise regarding the issues of cortisol testing, the administration of corticotropin, and the use of hydrocortisone.
5 ReferencesDjillali Annane, M.D.
Raymond Poincaré Hospital, F-92380 Paris, FranceJosef Briegel, M.D.
Ludwig-Maximilians-Universität München, 81366 Munich, GermanyCharles L. Sprung, M.D.
Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
sprung@cc.huji. ac. il 1
Cooper MS ,Stewart PM . Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003;348:727-734
Full Text | Web of Science | Medline2
Annane D ,Sebille V ,Troche G ,Raphael JC ,Gajdos P ,Bellissant E . A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000;283:1038-1045
CrossRef | Web of Science | Medline3
Matot I ,Sprung CL . Corticosteroids in septic shock: resurrection of the last rites? Crit Care Med 1998;26:627-630
CrossRef | Web of Science | Medline4
Annane D ,Sebille V ,Charpentier C , et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871
CrossRef | Web of Science | Medline5
Briegel J ,Forst H ,Haller M , et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single center study. Crit Care Med 1999;27:723-732
CrossRef | Web of Science | Medline
To the Editor:
Cooper and Stewart suggest that corticotropin stimulation be used to diagnose adrenal insufficiency in acutely ill patients, citing a trial involving patients with septic shock who were randomly assigned to receive either corticosteroids or placebo and in which only patients with a decreased cortisol response to corticotropin had a survival benefit from the use of corticosteroids.1 The incremental cortisol response to corticotropin has been established as a test of adrenal reserve in nonstressed patients2 but may lack adequate diagnostic accuracy in the critically ill.3 Assessment of an unstimulated cortisol level predicts clinical benefit from the administration of corticosteroids in acutely ill patients.4 In the trial previously cited, patients with a decreased cortisol response to corticotropin tended to have lower unstimulated cortisol levels (P=0.06).1
In acutely ill patients, the diagnostic value of the incremental cortisol response to corticotropin requires further evaluation. Hence, the diagnostic use of this test in the critically ill should currently be viewed with caution and an unstimulated cortisol level may provide sufficient information on which to base treatment decisions.
4 ReferencesNicholas A. Tritos, M.D., D.Sc.
Joslin Clinic, Boston, MA 02215
ntritos@caregroup.harvard. edu 1
Annane D ,Sebille V ,Charpentier C , et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871
CrossRef | Web of Science | Medline2
Streeten DH . What test for hypothalamic-pituitary-adrenocortical insufficiency? Lancet 1999;354:179-180
CrossRef | Web of Science | Medline3
Marik PE ,Zaloga GP . Adrenal insufficiency during septic shock. Crit Care Med 2003;31:141-145
CrossRef | Web of Science | Medline4
Rivers EP ,Gaspari M ,Saad GA , et al. Adrenal insufficiency in high-risk surgical ICU patients. Chest 2001;119:889-896
CrossRef | Web of Science | Medline
To the Editor:
Cooper and Stewart discuss the use of corticosteroids in patients with septic shock and highlight recent trial results.1 Benefits were apparent in a subgroup of patients (77 percent) who had a poor cortisol response to a corticotropin test, but fundamental design flaws may invalidate the reported results. Etomidate, a long-acting and powerful inhibitor of cortisol synthesis,2 was given to 72 patients enrolled during the first two years of that study and to an undetermined number thereafter.3 Sixty-eight of 72 etomidate-treated patients had a poor cortisol response. Drawing inferences about the effects of septic shock on adrenal function and clinical outcomes becomes problematic in the face of a profound drug-induced adrenal suppression.
In addition, the need for oral fludrocortisone replacement was discussed. This treatment has no clear pharmacologic rationale. When 200 mg of hydrocortisone per day was administered with it, fludrocortisone would contribute only 0.25 percent of the antiinflammatory activity and 3 percent of the mineralocorticoid activity of the regimen.4
Convincing evidence that corticosteroids will improve important clinical outcomes is not yet available. More work is required before their use is widely adopted in practice.
4 ReferencesRoxanna Bloomfield, M.B., F.R.C.A.
Michael MacMillan, M.B., F.R.C.A.
David W. Noble, B.Med.Biol., F.R.C.A.
Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, United Kingdom
david.noble@arh. grampian. scot. nhs. uk 1
Annane D ,Sebille V ,Charpentier C , et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871
CrossRef | Web of Science | Medline2
Absalom A ,Pledger D ,Kong A . Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia 1999;54:861-867
CrossRef | Web of Science | Medline3
Annane D ,Sebille V ,Bellissant E . Corticosteroids for patients with septic shock. JAMA 2003;289:43-44
CrossRef | Web of Science4
Schimmer BP, Parker KL. Adrenocorticotrophic hormone: adrenocortical steroids and their synthetic analogs: inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbard LE, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996:1459-85.
To the Editor:
Cooper and Stewart write that, in sepsis, the high levels of cytokines inhibit adrenal cortisol synthesis. This information is illustrated in Panel C of their Figure 1. To support this statement, the authors refer to a 1984 article by Catalano et al.,1 which does not, in fact, give any cytokine measurements. However, there are many publications that report the opposite mechanism and that implicate inflammatory cytokines such as interleukin-1, interleukin-6, or tumor necrosis factor in the stimulation of pituitary corticotropin and adrenal cortisol secretion during sepsis.2-4
4 ReferencesFlorence Riché, M.D.
Marie-Josèphe Laisné, M.D.
Arnaud Alves, M.D.
Hôpital Lariboisière, 75010 Paris, France
florence.riche@lrb. ap-hop-paris. fr 1
Catalano RD ,Parameswaran V ,Ramachandran J ,Trunkey DD . Mechanisms of adrenocortical depression during Escherichia coli shock. Arch Surg 1984;119:145-150
Web of Science | Medline2
Chrousos GP . The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 1995;332:1351-1362
Full Text | Web of Science | Medline3
Roh MS ,Drazenovitch KA ,Barbose JJ ,Dinarello CA ,Cobb CF . Direct stimulation of the adrenal cortex by interleukin-1. Surgery 1987;102:140-146
Web of Science | Medline4
Perlstein RS ,Whitnall MH ,Abrams JS ,Mougey EH ,Neta R . Synergistic roles of interleukin-6, interleukin-1, and tumor necrosis factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo. Endocrinology 1993;132:946-952
CrossRef | Web of Science | Medline
- Citing Articles (13)
Citing Articles
1
Prasanna Santhanam, Saba Faiz Saleem, Tipu Faiz Saleem. (2010) Diagnostic Predicament of Secondary Adrenal Insufficiency. Endocrine Practice 16:4, 686-691
CrossRef2
Brian H. Cuthbertson, Charles L. Sprung, Djillali Annane, Sylvie Chevret, Mark Garfield, Serge Goodman, Pierre-Francois Laterre, Jean Louis Vincent, Klaus Freivogel, Konrad Reinhart, Mervyn Singer, Didier Payen, Yoram G. Weiss. (2009) The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock. Intensive Care Medicine 35:11, 1868-1876
CrossRef3
Stephen F. Lowry. (2009) The Evolution of an Inflammatory Response. Surgical Infections 10:5, 419-425
CrossRef4
Vivek Moitra, Robert N. Sladen. (2009) Monitoring Endocrine Function. Anesthesiology Clinics 27:2, 355-364
CrossRef5
Marta Bondanelli, Maria Chiara Zatelli, Maria Rosaria Ambrosio, Ettore C. degli Uberti. (2008) Systemic illness. Pituitary 11:2, 187-207
CrossRef6
Diane Lipiner-Friedman, Charles L. Sprung, Pierre Fran??ois Laterre, Yoram Weiss, Sergey V. Goodman, Michael Vogeser, Josef Briegel, Didier Keh, Mervyn Singer, Rui Moreno, Eric Bellissant, Djillali Annane. (2007) Adrenal function in sepsis: The retrospective Corticus cohort study. Critical Care Medicine 35:4, 1012-1018
CrossRef7
Edward R. Sherwood, Daniel L. Traber. 2007. The systemic inflammatory response syndrome. , 292-309.
CrossRef8
Fekri Abroug, Lamia Ouanes-Besbes, Islam Ouanes, Noureddine Nciri, Fahmi Dachraoui, Fadhel Najjar. (2006) Adrenal insufficiency in severe West Nile Virus infection. Intensive Care Medicine 32:10, 1636-1639
CrossRef9
Nathan I. Shapiro, Michael D. Howell, Daniel Talmor, Dermot Lahey, Long Ngo, Jon Buras, Richard E. Wolfe, J Woodrow Weiss, Alan Lisbon. (2006) Implementation and outcomes of the Multiple Urgent Sepsis Therapies (MUST) protocol*. Critical Care Medicine 34:4, 1025-1032
CrossRef10
Jérome Aboab, Olivier Nardi, Diane Lipiner, Tarek Sharshar, Djillali Annane. (2006) Emerging drugs for the treatment of sepsis. Expert Opinion on Emerging Drugs 11:1, 7-22
CrossRef11
Djillali Annane. (2005) Glucocorticoids in the treatment of severe sepsis and septic shock. Current Opinion in Critical Care 11:5, 449-453
CrossRef12
Didier Keh, Charles L. Sprung. (2004) Use of corticosteroid therapy in patients with sepsis and septic shock: An evidence-based review. Critical Care Medicine 32:Supplement, S527-S523
CrossRef13
Philip E Knapp, Seth M Arum, James C Melby. (2004) Relative adrenal insufficiency in critical illness: a review of the evidence. Current Opinion in Endocrinology & Diabetes 11:3, 147-152
CrossRef
