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 occurs in roughly half of patients with septic shock and very occasionally in critically ill patients without sepsis.
“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].”
About half of patients with septic shock have decreased cortisol synthesis as assessed by response to the metyrapone test.
“As noted earlier, about half of patients with septic shock have decreased cortisol synthesis as assessed by response to the metyrapone test [64].”
Clinical studies find ACTH levels significantly lower in critically ill septic patients than in healthy volunteers.
“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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- 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 › Epidemiology › 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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