Endocrine Abstracts

The diagnosis of Cushing’s syndrome (CS) remains a major clinical challenge especially in a proportion of patients that have discordant results in the available tests. Although the measurement of 24-h urine free cortisol (UFC) is a useful test for the diagnosis of CS, 10–15% of patients have at least one measurement within the normal range and multiple measurements may be required in order to raise its sensitivity. In this study we sought to evaluate the value of the measurement of the cortisol to creatinine (UFCtoCr) ratio in morning urine samples collected over 42 consecutive days in patients with discordant results regarding UFC and low-dose-dexamethasone suppression test (LDDST). The determination of the reference range was based on morning urine samples provided by 19 healthy subjects. Eight patients with the clinical suspicion of mild CS were studied. Preceding diagnostic work-up had revealed a normal UFC (median 189, range 158–364 nmol/24 h) but an abnormal LDDST response (median 147, range 94–353 nmol/l) in all of them. The diagnosis of Cushing’s disease (CD) was subsequently confirmed histologically or on the grounds of sustained clinical and laboratory remission after transsphenoidal surgery. All patients provided daily collections of morning urine samples for 42 consecutive days. A broad variability in measured UFCtoCR ratios was noted in all patients across the 42-day period, with a number of values falling within the normal range. The percentage of ratios above the upper normal reference range varied between 37% and 100%, with abnormal ratios in more than 50% of the measurements noted in 7 out of 8 patients. This variability may account for the normal UFC measurements and multiple collections may be necessary in order to make the diagnosis. In these patients the collection of morning samples has a better diagnostic performance than a single UFC measurement but the LDDST remains the test with the highest diagnostic sensitivity. The value of the measurement of UFCtoCR ratios in the diagnosis of cyclic Cushing’s and in the differential diagnosis between CS and Pseudo-Cushing remains to be established.