Badshah I, Hadlow N, Brown S, Henley D.
Background: Cortisol is a glucocorticoid hormone with well-recognised patterns of secretion, including an ultradian rhythm which underpins a diurnal circadian rhythm of higher morning cortisol (morning acrophase) with night time nadir. Morning cortisol collection is important for assessment of adrenal sufficiency and levels from 300-500 nmol/L have been demonstrated in various studies to predict passing the Synacthen stimulation test (SST) with variable specificity ranging from 62-100%. Aim: Given the significant diurnal decline in cortisol across the morning, the aim of our study was to determine whether time specific reference intervals (multiples of the median – MoM’s) for cortisol would have utility in predicting SST outcome, reducing the number of unnecessary tests. Methods: We calculated individual MoMs for discrete time intervals across the morning between 7:00am and 12 midday and performed ROC curve analysis to determine 90% and 95% specifity cut-offs within each time interval.Results: A single 95% specificity threshold applied across the morning showed variable specificity for predicting SST outcome (range: 91-100%). Using a MoMs approach for each discrete time interval yields a more consistent specificity across the morning (range: 95-100% at 95% specificity). Individual MoMs for discrete time intervals optimised specificity without compromising sensitivity (range: MoMs 75-89% versus single cut-off 58-84% sensitivity).Conclusion: Compared to a single cut-off value for basal morning cortisol, time-specific MoMs gives a more reliable prediction of passing a SST.