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Diagnosis of Adrenal Insufficiency in Severe Sepsis and Septic Shock

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

Correspondence and requests for reprints should be addressed to Djillali Annane, M.D., Ph.D., Service de Réanimation, Hôpital Raymond Poincaré (AP-HP), Faculté de Médecine Paris Ile de France Ouest (UVSQ), 104 Boulevard Raymond Poincaré, 92380 Garches, France. E-mail: djillali.annane{at}rpc.aphp.fr

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 11-deoxycortisol levels before and after an overnight metyrapone stimulation. Adrenal insufficiency was defined by postmetyrapone serum 11-deoxycortisol levels below 7 µg/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 µg/dl), cortisol (< 9 µg/dl), and free cortisol (< 2 µg/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 µg/dl or less or cortisol of less than 9 µg/dl. The best predictors of normal adrenal response were cosyntropin-stimulated cortisol of 44 µg/dl or greater and cortisol of 16.8 µg/dl or greater.

Conclusions: In sepsis, adrenal insufficiency is likely when baseline cortisol levels are less than 10 µg/dl or delta cortisol is less than 9 µg/dl, and unlikely when cosyntropin-stimulated cortisol level is 44 µg/dl or greater or cortisol is 16.8 µg/dl or greater.

Key Words: corticol injection • free cortisol • corticotropin

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Adrenal insufficiency may be a frequent complication of critical illnesses such as severe sepsis, and may be associated with a worse outcome. Its diagnosis remains controversial. What This Study Adds to the Field Changes in serum total or free cortisol after corticotropin bolus can be used to detect adrenal insufficiency in septic patients.

 

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