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Preliminary investigation into the response of free cortisol to the low-dose corticotrophin test in patients with septic shock


Controversy exists around the use of total plasma cortisol and the high-dose adrenocorticotrophic hormone (ACTH) test for diagnosing relative adrenal insufficiency in sepsis [1, 2]. Our aim was to examine the response of bioactive free cortisol levels to stimulation with 1 μg synthetic ACTH in a cohort of patients with septic shock.


A prospective observational study at a tertiary intensive care facility. Patients with septic shock (n = 14) were enrolled. Measurements of free cortisol and total plasma cortisol were performed at baseline and at 30 and 60 minutes following injection of 1 μg synthetic ACTH (synacthen).


Free plasma cortisol and total plasma cortisol at baseline on day 1 were 39.7 (± 44.7) and 424.6 (± 232.8) nmol/l, respectively. The mean increments at 30 minutes of total cortisol and free cortisol were 157.3 (± 106) and 54.4(± 36) nmol/l, respectively. The mean percentage changes in total and free cortisol were 29.6% and 82.8%, respectively; P = 0.07. Relative adrenal insufficiency diagnosed by a total plasma cortisol response <250 nmol/l was present in 12 patients (85%), and in 13 patients (92%) by a free cortisol increment of less than 110 nmol/l.


To our knowledge these data represent the first set of information on free cortisol response to 1 μg synacthen. Although preliminary, the proportionally larger change in free cortisol in response to a low-dose synacthen stimulus may indicate a greater sensitivity for secondary adrenal insufficiency, and is consistent with previous observations [1]. These data support the suggestion that the traditional relative adrenal insufficiency criteria might need reconsideration. Further study is warranted to determine the clinical utility of this investigation.


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  2. Marik PE, et al.: Adrenal insufficiency during septic shock. Crit Care Med 2003, 31: 141-145. 10.1097/00003246-200301000-00022

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Cohen, J., Prins, J., Deans, R. et al. Preliminary investigation into the response of free cortisol to the low-dose corticotrophin test in patients with septic shock. Crit Care 12 (Suppl 2), P437 (2008).

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