Endocrine Abstracts (2013) 32 P32 | DOI: 10.1530/endoabs.32.P32

Diagnostic performance of first line biochemical tests to differentiate ACTH-ectopic syndrome among ACTH dependent Cushing's syndrome

Zhanna Belaya, Liudmila Rozhinskaya, Natalia Dragunova, Larisa Dzeranova, Svetlana Arapova, Evgenia Marova, Galina Kolesnikova & Galina Melnichenko


The National Research Center for Endocrinology, Moscow, Russia.


Introduction: This study evaluates the diagnostic accuracy of clinical features and first line routine screening tests to differentiate ACTH-ectopic syndrome from Cushing’s disease (CD).

Materials and methods: The retrospective clinical and biochemical presentations of 180 patients with histologically proven ACTH-dependent Cushing’s syndrome (CS) (159 CD, 21 ACTH-ectopic syndrome) were compared according to the cause of hypercortisolism. ROC-analysis was performed to estimate the diagnostic accuracy of the first line tests (2300 h serum cortisol, 24 h urinary free cortisol (24 h UFC) and ACTH rhythm in plasma) to differentiate ACTH-ectopic syndrome. A threshold for the test with the highest area under the curves (AUC) was chosen based on the maximum sum of sensitivity and specificity. Serum cortisol and plasma ACTH were assayed by electrochemiluminescence Cobas e601 Roche. 24 h UFC was measured by an immunochemiluminescence assay (extraction with diethyl ether) on a Vitros ECi

Results: The patients with ACTH-ectopic syndrome (in 15 cases bronchial carcinoid, in four – carcinoid of thymus, in one instance small cell carcinoma of the lung and in one – carcinoid of the appendix) had higher rates of low traumatic fractures (P=0.04), increased serum late-night cortisol, 24 h UFC, morning and evening ACTH and lower levels of potassium (P<0.01 for all parameters) vs CD. Late-night plasma ACTH showed the highest AUC (0.845 (95% CI 0.764–0.926)) to differentiate ACTH-ectopic syndrome from CD vs morning plasma ACTH – 0.790 (95% CI 0.673–0.908); late-night serum cortisol – 0.754 (95% CI 0.622–0.886) or 24 h UFC 0.619 (95% CI 0.481–0.758). A cut off value of 108.9 pg/ml for late-night ACTH yielded a sensitivity of 70.6% and a specificity of 81.7%.

Conclusions: Of all the clinical features and first line tests, the disturbance of the ACTH rhythm and high late-night plasma ACTH values in patients with proven CS is the most suggestive of ACTH-ectopic syndrome.