In the current work, we aimed to evaluate the association of clinical data of Cushing’s disease (CD) patients with USP8 mutation status and to study USP8-related molecular mechanisms connected to the regulation of corticotropinoma growth and activity. 35 CD patients were enrolled; the sequencing of exon 14 in USP8 revealed variants in eighteen adenomas, two of which were described for the first time in CD. USP8 variants were more common in women (94% vs. 76%; p = 0.001), and microadenomas and tumor recurrence were prevalent in the USP8-mutant group (44% vs. 29%; p = 0.04 and 44% vs. 22%; p = 0.0015). Preoperative ACTH and serum cortisol did not differ in the USP8-WT and USP8-mutant patients. All USP8-mutant adenomas were SST5-positive, and 73% of them were double-positive (SST5+/SST2+). A total of 50% of USP8-WT adenomas were double-negative (SST5−/SST2−), and 40% of them were SST5-positive. Analysis of transcriptome was performed for nine USP8-mutant and six USP8-WT adenomas and revealed the that the bidirectional dysregulation of Wnt signaling, including both the agonist RSPO2 and antagonist SFRP1, in the USP8-mutant corticotropinomas was downregulated. These alterations may indicate the existence of regulatory connections between USP8 enzyme activity, Wnt signaling, EGFR signaling and somatostatin receptors’ trafficking, which can explain, at least in part, the clinical manifestations of CD in patients with corticotropinomas harboring USP8 variants.

Persistent and recurrent hypercortisolism after transsphenoidal endoscopic surgery (TSS) is considered to be an urgent issue prompting the search for Cushing’s disease (CD) remission predictors. The goal was to find a combination of predictors that can forecast the remission of CD after TSS. A total of 101 patients with CD who had undergone TSS were included. One year after surgery, CD remission status was evaluated. Preoperative pituitary magnetic resonance imaging (MRI) data, preoperative results of a high-dose dexamethasone suppression test (HDDST) and morning serum cortisol level collected 24 h after TSS (24 h MSeC) were compared in patients with and without remission of hypercortisolism. Remission one year after TSS was confirmed in 63 patients. CD remission predictors one year after TSS were: adenoma size ≥ 3 mm in the absence of invasive growth and the suppression of serum cortisol ≥ 74% in the HDDST, 24 h MSeC ≤ 388 nmol/L. A total of 38 patients had three favorable values of detected predictors; all of them had CD remission one year after TSS. With long-term follow-up, 36 of them remained in remission. Patients who had no one favorable predictor had no remission of hypercortisolism one year after TSS. Our data confirmed the prospects of using a combination of selected predictors to forecast CD remission after TSS.

Introduction. Transsphenoidal adenomectomy (TSA) is the method of choice in the treatment of Cushing’s disease (CD), but remission of hypercorticism cannot be achieved in all patients. The search for predictors of CD remission after TSA remains to be an important challenge in the endocrinology today.Aim. To study the preoperative and postoperative data of patients with CD to identify the predictors of hypercorticism remission after TSA.Materials and methods. 101 patients with confirmed CD after TSA were included. One year after operation all patients were examined for the presence of hypercorticism remission and divided into two groups: with CD remission and its absence. In both groups’ preoperative pituitary magnetic resonance imaging (MRI) data, the results of preoperative high dose dexamethasone suppression test (HDDST) and the results of serum cortisol collected in the morning 2–3 days after surgery were compared.Results. One year after TSA, CD remission was confirmed in 63 patients (62.4%), whereas in 38 patients (37.6%) hypercortisolism persisted. Favorable predictors of CD remission were: the adenoma size > 3 mm without the invasive growth according to pituitary MRI (specificity 82.4%, sensitivity 82.8%), serum cortisol suppression ≥ 74% in preoperative HDDST (specificity 81.5%, sensitivity 86.3%), morning serum cortisol level in 2–3 days after surgery ≤ 388 nmol/l (specificity 79.3%, sensitivity 97.4%).Conclusions. Pituitary MRI data, the results of preoperative HDDST and morning serum cortisol in the 2–3 days after surgery can be used as predictors of CD remission.

Aim. To study the role of prognostic oral high-dose dexamethasone suppression test (HDDST) and pituitary MRI in the prognosis of Cushing’s disease (CD). remission after transsphenoidal endoscopic surgery (TSS). Material and methods. 59 patients with Cushing’s disease (9 men, 50 women, mean age 40 years (15-72) underwent TSS were included. Before the TSS HDDST and pituitary MRI were performed in all cases. Postoperative examination was done one year after surgery. Remission criteria were: combination of normal midnight serum cortisol levels, normal 24 hour urine free cortisol (UFC) excretion and serum cortisol suppression less than 50 nmol/l in 1-mg dexamethasone test or secondary adrenal insufficiency (the need for glucocorticoid replacement). The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was calculated by ROC-analysis. Results. One year after surgery CD remission was confirmed in 39 patients, whereas in 20 patients hypercortisolism persisted. The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was 72%. Test’s sensitivity and specificity were 82% and 84%, respectively. The probability of wrong prediction was 17% (p=0,0001). In our study, the results of TSS did not correlate with MRI adenoma size.

One of the main prognostic factors for meningioma recurrence is histological diagnosis with an assessment of tumor grade. Despite this, there are no clear microscopic criteria for recurrence prognosis in benign forms, and there is no common understanding of meningioma recurrence and continued growth clinical management. Objective. To evaluate neuroimaging, microscopic features and proliferative activity in meningioma recurrence and continued growth. Material and methods. Histological and immunohistochemical studies of tumor biopsies were performed in 16 patients with tumor progression who underwent surgery for recurrence and continued growth of intracranial meningiomas; the comparison group included 10 patients with newly diagnosed intracranial meningioma. All patients were performed pathomorphological and radiological examination assessment. Results. The average tumor volume in the meningioma progression group was 48.88±14.32 cm3; the average tumor volume was higher in the primary surgical treatment group — 51.51±14.48 cm3. Recurrent tumors were characterized by more pronounced cellular and tissue atypia, patterns of infiltrative growth with the involvement of large vessels. The meningioma proliferative activity, assessed by Ki-67(max) expression, was higher in the group with meningioma progression and amounted to 9.71±2.5%. Significant differences in the Ki-67 expression were noted by tumor localization, grade, and brain invasion (p<0.05) in the meningioma recurrence and continued growth group. Conclusion. Recurrent meningiomas are represented by different grade tumors, including benign typical meningioma (grade 1), which indicates the need for greater attention and patient follow-up with this pathology. There are differences in terms of grade progression and locally destructive growth in meningioma recurrence and continued growth. This indicates a more pronounced biological tumor aggression. The Ki-67 expression is an important prognostic factor in meningioma progression group.

Introduction. Meningiomas are common tumors of the central nervous system, most of which are benign. Anaplastic and atypical meningiomas, which together account for 25 % of all meningiomas, have a high recurrence rate even after gross total resection and radiotherapy, which determines a significantly worse prognosis. The mechanisms of recurrence remain poorly understood. Purpose. To assess the significance of arachnoid granulations in the recurrence of meningiomas; to present our own clinical case; to make the review of the literature on this topic. Materials and methods. We searched for publications in the Pubmed, EMBASE, Cohrane Library, and eLibrary databases published between the beginning of database management to February 2023 on the issue of the role of arachnoid granulation in meningioma reccurence. The materials of the desease history and results of histological examination of 71-year-old with intracranial meningioma who were treated in Almazov National Medical Research Center are used in this work. Results. The clinical case of intracranial meningioma surgery is described. Histological examination of the tumor revealed papillary meningioma, grade 3. Tumor growth of meningioma was found in the granulations of the arachnoid. According to the review the clinical case shows the importance of the arachnoid granulations in determining the clinical management for this group of patients.