Evaluation of Random Plasma Cortisol and the Low Dose Corticotropin Test as Indicators of Adrenal Secretory Capacity in Critically Ill Patients: A Prospective Study

Abstract

It is unclear whether a random plasma cortisol measurement and the corticotropin (ACTH) test adequately reflect glucocorticoid secretory capacity in critical illness. This study aimed to determine whether these tests provide information representative of the 24 hour period. Plasma cortisol was measured hourly for 24 hours in 21 critically ill septic patients followed by a corticotropin test with 1 μg dose administered intravenously. Serum and urine were analysed for ACTH and free cortisol respectively. Marked hourly variability in plasma cortisol was evident (coefficient of variation 8–30%) with no demonstrable circadian rhythm. The individual mean plasma cortisol concentrations ranged from 286±59 nmol/l to 796± 83 nmol/l. The 24 hour mean plasma cortisol was strongly correlated with both random plasma cortisol (r2 0.9, P<0.0001) and the cortisol response to corticotropin (r2 0.72, P<0.001). Only nine percent of patients increased their plasma cortisol by 250 nmol/l after corticotropin (euadrenal response). However, 35% of non-responders had spontaneous hourly rises >250 nmol/l thus highlighting the limitations of a single point corticotropin test. Urinary free cortisol was elevated (865±937 nmol) in both corticotropin responders and non-responders suggesting elevated plasma free cortisol. No significant relationship was demonstrable between plasma cortisol and ACTH. We conclude that although random cortisol measurements and the low dose corticotropin tests reliably reflect the 24 hour mean cortisol in critical illness, they do not take into account the pulsatile nature of cortisol secretion. Consequently, there is the potential for erroneous conclusions about adrenal function based on a single measurement. We suggest that caution be exercised when drawing conclusions on the adequacy of adrenal function based on a single random plasma cortisol or the corticotropin test.