• Jeremy Cohen, Antje Blumenthal, Gabriel Cuellar-Partida, David M Evans, Simon Finfer, Qiang Li, Johanna Ljungberg, John Myburgh, Elizabeth Peach, Joseph Powell, Dorrilyn Rajbhandari, Andrew Rhodes, Anne Senabouth, and Balasubramanian Venkatesh.
• The George Institute for Global Health, Sydney, Australia. cohenjeremy@me.com.
• Intensive Care Med. 2021 Sep 1; 47 (9): 974-983.

PurposeTo determine if adrenocortical gene expression is associated with clinical outcomes or response to corticosteroid treatment in septic shock.MethodsA pre-specified nested cohort study of a randomised controlled trial of hydrocortisone compared to placebo in septic shock. Blood was collected for RNAseq analysis prior to treatment with hydrocortisone or placebo. The expression of adrenocortical candidate genes related to pituitary releasing hormones, mineralocorticoid and glucocorticoid receptors, intracellular glucocorticoid metabolism and transport proteins was measured.ResultsFrom May 2014 to April 2017, 671 patients were enrolled in the nested cohort study, from which 494 samples were available for analysis. We found no evidence of an association between candidate gene expression levels and either 90-day mortality, 28-day mortality or time to shock reversal. We observed evidence of a significant interaction between expression and treatment group for time to shock reversal in two genes; GLCCI1 (HR 3.81, 95%CI 0.57-25.47 vs. HR 0.64, 95%CI 0.13-3.07 for hydrocortisone and placebo respectively, p for interaction 0.008) and BHSD1 (HR 0.55, 95%CI 0.28-1.09 vs. HR 1.32 95%CI 0.67-2.60, p for interaction 0.01).ConclusionsIn patients with septic shock, there is no association between adrenocortical candidate gene expression and mortality. Patients with higher expression of GLCCI1 who received hydrocortisone achieved shock resolution faster than those receiving placebo; conversely, patients who had higher expression of BHSD1 who received hydrocortisone achieved shock resolution slower than those who received placebo. Variation in gene expression may be a mechanism for heterogeneity of treatment response to corticosteroids in septic shock.© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

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