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1 . 2024

Assessment of possibilities for predicting persistent and recurrent course of Cushing’s disease


Cushing’s disease (CD) is a severe neuroendocrine disease caused by hypersecretion of adrenocorticotropic hormone (ACTH) by a pituitary tumor with clinical symptoms of endogenous hypercortisolism (EH). The «gold standard» of treatment CD is neurosurgery. In a quarter of all cases, surgical treatment does not lead to the development of laboratory and clinical remission, which suggests a persistent course of the disease. When the clinical and laboratory picture returns, it’s recurrence of the disease. Identification of predictors of persistent or recurrent course of the disease is the stage of forecasting and determining an algorithm for patient management.

Aim. To develop and evaluate a prognostic model of the risk of developing persistent and recurrent CD.

Material and methods. A prospective cohort study was conducted among 146 patients with confirmed CD. All patients underwent an analysis of EH activity in the preoperative and postoperative period. We analyzed blood cortisol (nmol/l), salivary cortisol at 23:00 (nmol/l), free cortisol in 24-hour urinary free cortisol (UFC, nmol/day), ACTH (pg/ml), and the degree of reduction of these hormones relative to the preoperative level was determined. All patients were divided into three groups according to disease status. The first group of patients (n=72; 49.3%) consisted of patients who were diagnosed with stable remission of CD. The second group of patients had persistent disease (n=38; 26%). The third group (n=36; 24.7%) consisted of patients with recurrent disease.

Results. To identify the most significant predictors of persistence and relapse, algorithms for stepwise inclusion/exclusion of covariates and an algorithm for analyzing covariates for all possible subsets in logistic regression models were applied. When assessing the risk of persistence, statistically significant differences were identified in ACTH, UFC, and blood cortisol after surgery compared to baseline (p<0.001), as well as the degree of their reduction (p<0.001). When the ratio of ACTH, UFC, and blood cortisol decreased by less than 50%, the risk of persistence of CD was most likely. Biochemical control parameters in both the preoperative and postoperative periods did not determine the risk of recurrence of CD.

Conclusion. Risk factors for persistence and recurrence vary significantly in patients with CD. The most reliable risk factors for persistence are a decrease in the levels of ACTH, UFC and blood cortisol relative to the preoperative period. Risk factors for relapse have not been determined. The use of a specific CD prediction model is necessary to determine an individual patient monitoring strategy.

Keywords:Cushing disease; endogenous hypercortisolism; persistent course; recurrent course; modelling; prediction

Funding. The study had no sponsor support.

Conflict of interest. The authors declare no conflict of interest.

For citation: Andreeva A.V., Antsiferov M.B. Assessment of possibilities for predicting persistent and recurrent course of Cushing’s disease. Endokrinologiya: novosti, mneniya, obuchenie [Endocrinology: News, Opinions, Training]. 2024; 13 (1): 16–26. DOI: (in Russian)


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Ametov Alexander S.
Honored Scientist of the Russian Federation, Doctor of Medical Sciences, Professor, Head of Subdepartment of Endocrinology, Head of the UNESCO Network Chair on the subject «Bioethics of diabetes as a global problem» of the Russian Medical Academy of Continuous Professional Education (Moscow)

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