Endocrine Abstracts

Background: Cushing’s syndrome (CS) is caused by endogenous cortisol excess and is associated with significant morbidity. Twenty-four-hour urinary cortisol is one of the most useful tools to diagnose CS although it has limitations, especially in “mild” and “subclinical” forms of cortisol excess. We hypothesized that given the diurnal rhythm of physiological cortisol secretion, night-time urinary glucocorticoid excretion should be lower than day-time excretion, which could facilitate more sensitive detection of cortisol excess with an overnight urine collection.

Methods: Prospective study comparing the urinary steroid profiling of patients with different degrees and aetiologies of cortisol excess to controls. Subjects provided an overnight urine collection and a day-time urine collection. Urine samples were analysed by liquid chromatography-tandem mass spectrometry quantifying 15 distinct adrenal steroids. The night-time and day-time steroid excretion rates were compared to the conventional 24-h urine excretion.

Results: We included patients with overt CS (N=11), mild autonomous cortisol excess (MACE) in the context of adrenal incidentaloma (N=17), nonfunctioning adrenal incidentalomas (N=22), and sex- and age-matched healthy controls (N=28). Steroid excretion in controls reflected the diurnal pattern of adrenal steroid secretion, with lower night-time than day-time excretion of glucocorticoid metabolites and 11β-hydroxyandrosterone, the metabolite of the major adrenal androgen 11β-hydroxyandrostenedione. Overt CS showed significantly increased night-time urinary cortisol excretion and, in contrast to 24-h cortisol excretion, no overlap between overt CS, MACE and controls. Both patients with overt adrenal CS and MACE had significantly decreased night-time androgen excretion in comparison to ACTH-dependent CS.

Conclusions: The timed overnight urinary collection performs equivalent to the current reference standard 24-h collection, with improved performance of urinary cortisol in patients with overt CS. The simultaneous analysis of multiple adrenal steroids is a promising tool for the stratification of patients with different degrees of cortisol excess and for the differential diagnosis of CS.