Objectives: To investigate the agreement between the calculated free cortisol levels according to widely applied Coolens and adjusted Södergård equations with measured levels in the critically ill. Design and methods: A prospective study in a mixed intensive care unit. We consecutively included 103 patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250. μg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin and albumin were assessed. Free cortisol was estimated by the Coolens method (C) and two adjusted Södergård (S1 and S2) equations. Bland Altman plots were made. Results: The bias for absolute (t. = 0, 30 and 60. min after ACTH injection) cortisol levels was 38, - 24, 41. nmol/L when the C, S1 and S2 equations were used, with 95% limits of agreement between - 65-142, - 182-135, and - 57-139. nmol/L and percentage errors of 66, 85, and 64%, respectively. Bias for delta (peak-baseline) cortisol was 14, - 31 and 16. nmol/L, with 95% limits of agreement between - 80-108, - 157-95, and - 74-105. nmol/L, and percentage errors of 107, 114, and 100% for C, S1 and S2 equations, respectively. Conclusions: Calculated free cortisol levels have too high bias and imprecision to allow for acceptable use in the critically ill.

Affinity constants, Coolens method, Cortisol-binding globulin, Critical illness related corticosteroid insufficiency, Equilibrium dialysis, Free cortisol, Relative adrenal insufficiency, Södergard equation
dx.doi.org/10.1016/j.clinbiochem.2015.07.014, hdl.handle.net/1765/92190
Clinical Biochemistry
Department of Intensive Care

Molenaar, N, Groeneveld, A.B.J, & de Jong, M.F.C. (2015). Three calculations of free cortisol versus measured values in the critically ill. Clinical Biochemistry, 48(16-17), 1053–1058. doi:10.1016/j.clinbiochem.2015.07.014