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

Introduction

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.

Methods

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).

Results

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.

Conclusion

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.

References

  1. 1.

    Ho JT, et al.: Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab 2006, 91: 105-114. 10.1210/jc.2005-0265

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    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, P437 (2008). https://doi.org/10.1186/cc6658

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Keywords

  • Cortisol
  • Septic Shock
  • Plasma Cortisol
  • Adrenal Insufficiency
  • Cortisol Response