Context.Patients with Cushing's syndrome (CS) of any etiology experience a number of physical and psychological symptoms which impact negatively on healthrelated quality of life (HRQoL).Subjects and methods. HRQoL was measured using CushingQoL questionnaire.Results. The first part of our study was a crosssectional analysis of 141 patients with CS over a 10-year period. CushingQoL score was lower in pituitary CS compared to adrenal CS. Remission and older age were associated with better outcome on item 7 (physical appearance anxiety). In a multivariate regression analysis after adjustment for etiology, remission status, age, UFC, duration of hypercortisolism and presence of hypercortisolism-associated comorbidities the female gender was the only negative predictor associated with poorer outcome on each of the three scores. The presence of hypercortisolism-associated comorbidities independently predicted poorer outcome on the psychological and the global subscales.The second part of our research was a prospective study of 27 patients with adrenal adenoma. Achievement of remission independently predicted improvement of the total score of any patient. Conclusion.Studying in details and understanding the mechanisms of the impaired HRQoL in patients with CS is the only way to become aware of the problem and create methods that could help these patients.

Cushing's syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients - the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS). Pituitary surgery was applied to 242 patients with Cushing's disease (CD) with initial remission rate of 74% of which 10% relapsed. Approximately 36% manifested with active disease during the long-term follow-up (26% with persistent disease, 10% relapses) most of which were subjected to a secondary treatment (13.6% to pituitary resurgery, 14% to pituitary radiotherapy, and 5.4% to bilateral adrenalectomy). A total of 294 CD patients received medical therapy with overall remission rates for the most commonly used drugs: dopamine agonists 20%, pasireotide 30%, and ketoconazole 63%. Significant improvement of results was achieved by combining drugs with different mechanisms of action. Regardless of the progress in the neurosurgery and radiotherapy techniques and new drugs discovery, the management of patients with CS remains a real challenge for physicians. Not only patients with adrenal carcinoma but also significant percentage of subjects with persistent and recurrent Cushing's disease often require a polymodal approach and the efforts of a multidisciplinary highly qualified, experienced, and motivated team in order to achieve a long-term remission.

Purpose: The aim of the present work was to analyse and identify differentially expressed miRNAs in Bulgarian patients with non-functioning pituitary adenomas (NFPA). The relationship between deregulated miRNAs and tumor size, invasiveness, and recurrence was determined.Methods: Twenty patients with NFPAs were selected and fresh pituitary tumor tissues were collected. RNA containing miRNAs were isolated using miRNAeasy mini kit and analysed with LNA miRNA Cancer Focus PCR Panel (Qiagen) by quantitative real-time PCR. Results: Three miRNAs (miR-210-3p, miR-149-3p and miR-29b-3p) were deregulated in invasive compared to non-invasive NFPAs. Differential expression of 4-miRNA signature - miRNA-17, miR-19, miR-106a and miR-20 was informative as a recurrence biomarker. ROC analysis showed that the selected miRNAs could be used as potential biomarkers for the diagnosis, prognosis and therapy monitoring of NFPAs.Conclusion: In this pilot study, we selected a unique miRNA expression profile correlating with NFPA invasiveness and recurrence. Moreover, some of the selected miRNAs are reported for the first time in patients with NFPAs and might elucidate the molecular mechanisms involved in pituitary pathogenesis. The selected miRNAs showed a promising biomarker potential and could be studied for future miRNAs-based anti-NFPAs therapy.