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Diagnosis of Adrenal Insufficiency in Severe Sepsis and Septic Shock
Abstract
RATIONALE: Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by a more accurate diagnostic standard. OBJECTIVE: We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin stimulation test, and the prevalence of sepsis-associated adrenal insufficiency. METHODS: This was an inception cohort study. MEASUREMENTS AND RESULTS: In two consecutive septic cohorts (n = 61 and n = 40), in 44 patients without sepsis and in 32 healthy volunteers, we measured (1) serum cortisol before and after cosyntropin stimulation, albumin, and corticosteroid-binding globulin levels, and (2) serum corticotropin, cortisol, and 11beta-deoxycortisol levels before and after an overnight metyrapone stimulation. Adrenal insufficiency was defined by postmetyrapone serum 11beta-deoxycortisol levels below 7 microg/dl. More patients with sepsis (31/61 [59% of original cohort with sepsis] and 24/40 [60% of validation cohort with sepsis]) met criteria for adrenal insufficiency than patients without sepsis (3/44; 7%) (p < 0.001 for both comparisons). Baseline cortisol (< 10 microg/dl), Delta cortisol (< 9 microg/dl), and free cortisol (< 2 microg/dl) had a positive likelihood ratio equal to infinity, 8.46 (95% confidence interval, 1.19-60.25), and 9.50 (95% confidence interval, 1.05-9.54), respectively. The best predictor of adrenal insufficiency (as defined by metyrapone testing) was baseline cortisol of 10 microg/dl or less or Delta cortisol of less than 9 microg/dl. The best predictors of normal adrenal response were cosyntropin-stimulated cortisol of 44 microg/dl or greater and Delta cortisol of 16.8 microg/dl or greater. CONCLUSIONS: In sepsis, adrenal insufficiency is likely when baseline cortisol levels are less than 10 microg/dl or delta cortisol is less than 9 microg/dl, and unlikely when cosyntropin-stimulated cortisol level is 44 microg/dl or greater or Delta cortisol is 16.8 microg/dl or greater.
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“Altered ACTH synthesis in response to metyrapone was observed in roughly half of patients with septic shock and very occasionally in critically ill patients without sepsis [64].”
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“As noted earlier, about half of patients with septic shock have decreased cortisol synthesis as assessed by response to the metyrapone test [64].”
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“Compared with healthy volunteers, clinical studies have found ACTH levels to be significantly lower in critically ill septic patients [14,64,65].”
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Metadata
- Authors
- Annane, D., Maxime, V., Ibrahim, F., Alvarez, J. C., Abe, E., & Boudou, P.
- Affiliations
- Hôpital Lariboisière (FR)
- Service de Réanimation and Service de Biochimie-Pharmacologie, Hôpital Raymond Poincaré, Faculté de Médecine Paris Ile de France Ouest, Garches; and Service de Biochimie Hormonale, Hôpital Saint Louis, Faculté de Médecine Saint Louis Lariboisière, Paris, France
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12
- Volume
- 174
- Issue
- 12
- Pages
- 1319-1326
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2007130516
- Cited by
- 327
- References
- 33
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 11 · 2022: 4 · 2021: 8 · 2020: 13 · 2019: 13 · 2018: 6 · 2017: 13 · 2016: 13 · 2015: 19 · 2014: 20 · 2013: 19 · 2012: 25
- FWCI
- 20.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- adrenal insufficiency, sepsis, septic shock, ACTH stimulation test, cortisol, ACTH, diagnostic criteria, critically ill patients, likelihood ratios, corticosteroid-binding globulin, albumin, free cortisol, 11beta-hydroxylase deficiency, ACTH deficiency
- MeSH terms
- Adrenal Insufficiency, Adrenocorticotropic Hormone, Aged, Cosyntropin, Female, Humans, Hydrocortisone, Male, Metyrapone, Middle Aged, Serum Albumin, Shock, Septic, Transcortin, Sepsis
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