Medicamental treatment of Itsenko-Cushing’s disease. The current state-of-the art

Abstract

Itsenko-Cushing’s disease (ICD) is a severe progressive neuroendocrine pathology characterized by the heterogeneous clinical picture and the high risk of complications. The main goals of ICD therapy include the total removal or the pituitary neoplasm or the reduction of its volume and/or stabilization of its growth, normalization of the cortisol level and secretion rhythm, the achievement of reverse development of clinical manifestations, and the retention of the pituitary hormonal function with a minimal risk of relapses. At present, both the improved methods for diagnostics of ICD and the development of its pharmacotherapy are needed. In the routine clinical practice, ICD is usually treated with the medicines of the following groups: blockers of glucocorticoid receptors and steroidogenesis, dophamine receptor antagonists, and multi-ligand somatostatin analogs. The evidence-based substantiation for the use of the above preparations was provided by the retrospective studies with the description of a series of cases which substantially restricts the reliable interpretation of the data on the effectiveness and safety of various medicines applied to manage the patients presenting with Itsenko-Cushing’s disease. The multi-ligand somatostatin analog pasiretoide is the sole preparation approved for the treatment of adult patients suffering ICD whose surgical treatment is either ineffective or impossible. The evaluation of the effectiveness and safety of pasiretoide therapy is based on the results of the prospective randomized double-blind classical study in which two doses of pasiretoide were used. By month 6 after the onset of the treatment with pasiretoide, the median of the daily decrease of the urinary cortisol level in the patients with ICD was 47.9%. The safety profile of this medication proved to be similar with that of other somatostatin analogs, with the exception of the higher frequency of hyperglycemia. Pasiretoide, like other somatostatin analogs, most frequently caused such adverse reactions as gastrointestinal disorders. At the same time, it ensured the stable reduction of the cortisol level by suppressing the ACTH production, and thereby decreased the main manifestations of hypercortisolism, induced clinical and hormonal remission, and improved the quality of life of the patients suffering Itsenko-Cushing’s disease.