Urinary free cortisol is an independent predictive factor for early distinction between ectopic ACTH secretion and pituitary Cushing’s disease

Furnica, Raluca-Maria;Nachit, Marine;Collard, Alix;Cornelis, Frank;Maiter, Dominique;et.al.
(2023) 25th European Congress of Endocrinology (ESE - European Society of Endocrinology) — Location: Istanbul, Turkey (13.May.2023)

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(en) Introduction: The poor prognosis of patients with Cushing’s syndrome due to ectopic ACTH secretion (ECS) requires prompt diagnosis and management of the disease. Objectives: To find clinical and biological differences between ECS and pituitary Cushing’s disease (CD) at diagnosis and to determine whether any of them may be a potential predictor for early suspicion of ECS. Methods: This was a retrospective case-nested study of 18 patients with ECS diagnosed and treated between 1993 and 2017, compared with 36 patients with proven CD and matched for the time of diagnosis. Results: ECS occurred more frequently in men (13/5 vs. 10/26) and at an older age (53.4 ± 17.3 vs. 43.1 ± 13.9) than CD. In most patients (89%) the source of ectopic ACTH secretion was identified by thoraco-abdominal CT. No significant difference was found in the prevalence of symptoms and signs of hypercortisolism between the two groups. We found that potassium level ≤ 3.65 mmol/l had sensitivity and specificity of 77%, and LDH level greater than 1.28xULN had a sensitivity of 69% and a specificity of 68% for the diagnosis of ECS. Both parameters were correlated with 24-hour urinary-free cortisol (UFC) which was higher in the ECS group (median: 1127 µg/24h) compared to the CD group (216 µg/24h, P<0.05). On univariate analysis, an older age at diagnosis, male sex, lower serum potassium, higher LDH and higher UFC values were significant predictors of ECS. Male sex increased the relative risk of ECS by 6.8 times and hypokalemia increased this risk by 52 times for each 1.0 mmol/l-decrease in serum potassium. However, only UFC (expressed as log10) was kept as an independent predictive factor in the multivariate analysis (P=0.0009), and a discriminant decision-tree approach showed that a UFC level ≥ 633 µg/24h (10.5-fold the upper limit of normal) was the best cut-off with a sensitivity of 87% and a specificity of 92% for the diagnosis of ECS. There was no difference between the two groups in terms of complications related to hypercortisolism but patients with ECS had a lower remission rate and a higher mortality. Conclusions: While severe hypokalaemia and higher LDH values translate a more severe degree of hypercortisolism in patients with ECS, 24h UFC at diagnosis appears to be the main independent predictor of ECS, with the best cut-off value determined at 10.5-fold the ULN, above which clinicians should rapidly suspect ECS and perform the appropriate work-up including thoraco-abdominal CT.
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Furnica, R.-M., Nachit, M., Collard, A., Cornelis, F., Alexopoulou, O., & Maiter, D. (2023). Urinary free cortisol is an independent predictive factor for early distinction between ectopic ACTH secretion and pituitary Cushing’s disease. Endocrine Abstracts, 90, 391. https://hdl.handle.net/2078.5/27237 (Original work published 2023)