Young patients with CS have a low TBS. However, the only predictor of low traumatic fracture is the severity of the disease itself, indicated by high 24hUFC levels.
This study estimates diagnostic performance of late-night salivary cortisol (LNSC) as measured by automated electrochemiluminescence immunoassay (ECLIA), evaluates the clinical implication of two consecutive LNSC measurements, and compares its accuracy with enzyme-linked immunosorbent assay (ELISA) and serum cortisol after low-dose dexamethasone suppression test (DST) in obese and overweight patients referred for suspected Cushing's syndrome (CS). One hundred twenty three consecutive obese and overweight referred patients and 98 healthy volunteers provided two saliva samples collected at 23:00 using a Salivette (Sarstedt, Germany), assayed by ECLIA (Cobas e601) and ELISA. The patients underwent DST and were further evaluated until CS was pathologically confirmed (n = 45) or excluded. Diagnostic performance of LNSC was evaluated by receiver operating characteristic (ROC) analysis. The total areas under the curve (AUC) were calculated to compare the different tests. We found that a cut-off value of 9.4 nmol/l can differentiate CS among obese and overweight patients with sensitivity of 84.4 % (95% CI 71.2-92.2), specificity of 92.3 % (95% CI 84.2-96.4), and diagnostic odds ratio of 65.1 (95% CI 20.4-207.6). No difference was found between AUCs from the first, second, and the mean from the two LNSC measurements (ECLIA), LNSC (ELISA), or DST. The single LNSC (ECLIA) and DST improved the sensitivity and specificity for concordant results up to 100 and 97.4 %, respectively. In conclusion, due to its automation and its comparable diagnostic performance, ECLIA is preferable as a first-line LNSC screening test for CS. The initial use of single LNSC followed by DST provides better diagnostic performance for concordant results.
Of all the tested proteins (sclerostin, Dkk1, SFRP1), only sclerostin showed a significant difference when contrasting CS with healthy subjects. Hypercortisolism might prevent the down-regulation of sclerostin. Targeting sclerostin seems to be a promising therapeutic approach to treating osteoporosis in patients with CS.
Nighttime salivary cortisol (NSC) has been suggested to be a useful diagnostic test for Cushings syndrome (CS). However, the reference range and cut-off value are assay-specific and discordant. The goal of this study was to assess the analytical performance of automated elecrochemiluminiscence immunoassay method (ECLIA) in CS. Ninety eight healthy volunteers and 123 obese patients including 45 proved to be CS provided salivary samples collected by them at 23:00 using Sallivette. Two hundred and five subjects collected salivary samples for two consecutive days and samples from 197 subjects were frozen to perform Enzyme-linked immunosorbent assay (ELISA). Obese patients underwent the 1-mg overnight dexamethasone suppression test (1-DST). CS was confirmed by the histologic diagnosis after surgical treatment or autopsy. The reference range for healthy volunteer has been set 0,5-9,4 nmol/l. Reproducibility was assessed in all subjects by a day-to-day variability and reflected by an intraclass correlation coefficient of 0,785. The cut-off value of 9,4 nmol/l has been suggested to differentiate CS among obese patients to achieve sensitivity of 84,4% (95%confidence interval 71,2-92,2%); specificity of 92,3% (95%CI 84,2-96,4%) and diagnostic odds ratio 65,1 (95% CI 20,4-207,6). Likelihood ratio positive was 11,0 (95% CI 5,0-23,9), with a likelihood ratio negative of 0,17 (95%CI 0,08-0,33). The comparison of the total areas under the ROC-curve for the measurement of NSC once, twice with mean level by ECLIA, the same samples by ELISA and 1-DST have not shown any statistically significant difference among the tests performance. Conclusion: Based on its remarkable reproducibility, easy noninvasive nature, automated assay and at least similar diagnostic performance, NSC measured by ECLIA on Cobas e601 is a preferable first-line screening test for CS.
Aims: this study evaluates the most common associations of symptoms and complications in patients with Cushing’s syndrome (CS) in order to choose a potential population to be screened for CS and estimates the diagnostic accuracy of first line screening tests (cortisol, ACTH) to differentiate ACTH-ectopic CS from Cushing’s disease. Materials and Methods: The clinical data of 259 patients with proven CS during 2001–2011 was analyzed. The clinical presentations of 197 patients (159 Cushing’s disease, 28 ACTH-ectopic CS and 10 cases of benign cortisol-secreting adrenal adenoma) were compared according to the cause of hypercortisolism. ROC-analysis was performed to estimate the diagnostic accuracy of the first line tests (cortisol, ACTH) to suggest ACTH-ectopic CS. A threshold for the test with the highest area under the curves was chosen based on the maximum sum of the sensitivity and specificity. Results: The most frequent complaints were related to fatigue, muscle weakness, weight gain and changes in appearance (facial plethora and fullness, striae). Among the complications of CS the most frequent were being overweight or obese (71%), hypertension (63%), dislipoproteinemia (41%), low traumatic fractures (43%) and steroid-induced diabetes (31%). In women, 16% were older than 50, in those who were younger amenorrhea was registered in 43%. The patients with ACTH-ectopic CS had higher rate of low traumatic fractures (p=0.04), increased serum late-night cortisol, 24 hours urinary free cortisol, morning and evening ACTH and lower levels of potassium (p0.01 for all parameters). Plasma late-night ACTH measurements showed the highest AUC (0,811 (95% CI 0,712–0,909)) to differentiate ACTH-ectopic CS from Cushing’s disease. A cut off value of 108.9 pg/ml for late-night ACTH yielded a sensitivity of 60,7% and a specificity of 79%. Conclusions: patients with a coexistence of obesity, muscle weakness, fatigue, some components of metabolic syndrome and especially low traumatic fractures should be screened for CS. High plasma late night ACTH values in patients with proven CS value suggest ACTH-ectopic syndrome.
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